medicaledition

Diagnosis, Treatmentand Prevention of theDiabetic Foot Syndrome

Wundbehandlung

2

Published byPAUL HARTMANN AGD-89522 Heidenheimhttp://www.hartmann.info

ByDr. med. Stephan MorbachSpecialist for Internal MedicineMarienkrankenhausSoest, Germany

English translation with theassistance ofMr. Martin Memmert, MD, PhDBS (Phil), MRCS Ed.Dr. Lachlan Arblaster,BSC, MBCHB, PhD

1st edition in German December 2000© PAUL HARTMANN AGISBN 3-929870-29-0

1st edition in English March 2004ISBN 3-929870-34-7

3

Table of contents

Page

Preface 5

Foreword 6

Diabetes mellitus - an introduction 7

– Diagnosis and classification of diabetes mellitus 7– Treatment and self-monitoring of diabetes mellitus 9– Secondary complications of diabetes mellitus 11

Definition and history of the diabetic footsyndrome 13

Epidemiology of the diabetic foot syndrome 16

Socio-economic significance of the diabetic footsyndrome 20

– Costs due to foot complications in diabetics 20– Psychological aspects and effect on quality of life 22

Risk factors for foot complications in diabetics 24

Concurrent diseases in diabetics with footcomplications 32

Diagnosis and differential diagnosis of thediabetic foot syndrome 35

– Diagnosis of sensorimotor and autonomic diabeticneuropathy and diabetic neuropathicosteoarthropathy 35

– Diagnosis of arterial occlusive disease 40– Classification of diabetic foot lesions 45

Basic principles of the treatment of diabeticfoot lesions 50

– Possibilities of pressure relief 50– Structured wound treatment and importance of

interactive wound dressings 52– Moist wound treatment 60– Treatment of infection 68

4

– Vascular and surgical interventions in the 71diabetic foot syndrome

– Importance of adjunctive treatment methods 76Hyperbaric oxygen therapy (HBO) 76Use of growth factors and bio-engineered tissues 78Biomechanical wound treatment 79

Tertiary prevention of the diabetic foot syndrome 81

– Effects of educating patients at risk 81– Importance of professional foot care 84– Provision of adapted footwear for diabetics 87– Structures for screening, treatment and after-

care of patients with diabetic foot syndrome 93– The diabetic foot: a global problem 98

Summary and prospects 101

Definitions and explanations 103

Abbreviations 106

Proposed further reading 107

References 108

5

Preface

We warmly welcome Dr. Stephan Morbach’s practicalbook on the diagnosis, management and preventionof diabetic foot problems. Over the past two decades,interest in this “Cinderella” specialty has increased.Numerous diabetic foot conferences have beenorganised and books and papers written. However,this book is a very useful addition to the literature.

The diabetic foot is a great problem world-wide, andpatients with diabetic foot disease are at very high riskof major amputation of a leg. In this volume, Dr. Morbachdescribes with clarity and precision, the interventionsneeded to improve outcomes for patients.

The book is beautifully illustrated by colour photographs.It is compact enough to be easily portable, and will beuseful both for community physicians and healthcareworkers as well as for multi-disciplinary, hospital-basedteams. The contents are very efficiently organised,and Dr. Morbach has not confined himself to commonareas of management, but also leads the reader throughoften neglected realms of psychological and socio-economic aspects, quality of life and epidemiology. How-ever he does not neglect the more practical aspectsof classification, risk factors, diagnosis and managementof patients with neuropathic and ischaemic ulcers, in-fections and necrosis. Wound care, dressings and use ofadvanced products such as living human skin equiva-lents are covered in detail, as are the management ofperipheral vascular disease, Charcot’s osteoarthropathyand pressure off-loading

This very practical book will be valued by all members ofthe diabetic foot team, be they physicians, surgeons,podiatrists, nurses or orthotists, working in community orhospital and should help to improve outcomes fordiabetic foot patients.

Michael Edmonds, Alethea Foster,MD, FRCP BA (Hons) DipPodMConsultant Physician Head Clinical Specialist Podiatrist

6

Foreword

Foot lesions affect more than 10% of patients with diabetesmellitus at some point in their life and are amongst themost dreaded complications of this disease. They cancause prolonged periods of immobility and discomfortand some never heal. Year after year, one in every 200diabetics loses a leg. The cost of foot ulcerations to theindividual and to society are considerable.

One of the reasons why foot injuries in diabetics representsuch an extraordinary problem is the large number ofdifferent factors that contribute to the aetiology and pro-gression of such lesions. Another relates to the manage-ment and treatment of diabetic foot ulceration. Optimumtreatment assumes the knowledge and experience ofa specialist multidisciplinary team, but such teams areunfortunately not widely available. The majority of all footinjuries in diabetics, however, are treated by medicalprofessionals who have neither received specific trainingnor have sufficient experience. This book has beenwritten for them. It is intended as a practical guide to thediagnosis and management of the lesions found in thediabetic foot.

Another section outlines the strategies for prevention ofsuch lesions. This book is based on experience withdiabetic patients in the outpatient foot clinic and on thewards of the Marienkrankenhaus in Soest (Germany)over the past eight years and on the knowledge andexperience imparted to me by the “Greats” of the diabeticfoot, such as Prof. Ernst Chantelau (Düsseldorf) andDr. Mike Edmonds (London).

Many questions relating to the diabetic foot still remainand many procedures have yet to be scientificallyconfirmed. This book is nevertheless an attempt tocombine practical guidelines with the current level ofknowledge on the subject.

Dr. Stephan Morbach

7

Diabetes mellitus –an introductionDiagnosis and classification of diabetes mellitus

Over the past few decades considerable knowledgehas been acquired about the aetiology and patho-physiology of diabetes mellitus. This knowledge placesa burden on the individual and society – because with-out doubt it is a very common, serious and cost-inten-sive, chronic disease. There are now many options interms of diagnosis and treatment to help sufferers. Manystudies have been directed at improving the meta-bolic status and treating the secondary complications ofdiabetes.

Despite these encouraging developments, there areunfortunately clear indications that a large number ofpatients with diabetes mellitus are at present undiagnos-ed and effective treatment programmes have yet tobe implemented universally. Improved detection ratesand the greater incidence of the disease will increasethe costs of diabetes dramatically in the next few decad-es. In the years between 1958 and 1993, the numberof people diagnosed with diabetes multiplied five-fold1.In 1995,135 million patients world-wide were living withdiabetes mellitus. By the year 2025 it is estimated thatthis figure will have increased to more than 300 million2.In Germany it may be assumed that there are currentlyat least 4 million known diabetics (5% of the population)and a further 3 to 4 million who are undiagnosed3.

Diabetes mellitus is a chronic metabolic disorder, pre-dominantly of carbohydrates, which has hereditary andenvironmental factors. According to the criteria of theWHO and the ADA (American Diabetes Association) of19974, a diagnosis can be established on the basis offasting plasma glucose levels of:1. 7.8 mmol/L (126 mg/dl) or above (with or without thepresence of the classic signs, such as polydipsia, poly-uria, tiredness, unexplained weight loss or pruritus).2. 11.1 mmol/L (200 mg/dl) and above measured at ran-dom and coexisting with the disease symptoms mention-ed previously3. 11.1 mmol/L measured two hours after a standardisedoral glucose tolerance test.

8

Under this classification, four types of diabetes may bedistinguished. Type 1 diabetes involves destruction ofthe pancreatic insulin-producing cells, usually resulting inan absolute insulin deficiency. Type 2 diabetes covers abroad range from marked insulin resistance with relativeinsulin deficiency to a marked impairment of insulinsecretion with slight insulin resistance. Type 3 relates togenetic, endocrinological, infectious and immunologicalunderlying diseases, diseases of the pancreas andiatrogenic or chemically induced forms. Type 4 (gesta-tional diabetes) occurring during pregnancy anddisappearing again post partum. Type 1 and type 2 arethe most common.

Well over 80% of all diabetics can be classified astype 21.

The distinction between type1 and type 2 diabetes basedpreviously on age of onset (“juvenile diabetes”, “senilediabetes”) is difficult to make in individual cases. In thefollowing situations, the diagnosis of type 1 diabetes issuggested, even in more advanced age:1. Normal bodyweight with further weight loss2. Absence of family history of diabetes mellitus3. A labile metabolic status on oral antidiabetic

medication4. The appearance of ketone bodies in the urine5. The detection of auto-antibodies to pancreatic cells or

their components (GAD = Glutamic Acid Decar-boxylase; ICA = Islet Cell Antibodies) in the blood5

suggest a diagnosis of type 1 diabetes, even witha more advanced age of onset.

Diagnostic guideline values for establishing diabetes mellitus (ADA 1997)

Fasting Random blood Oral glucoseplasma glucose sugar tolerance test

(75 g glucose)

Diabetes mellitus ≥7.0 mmol/L ≥ 11.1 mmol/ L ≥ 11.1 mmol/ Lwith symptoms after 2 hours

Impaired glucose ≥7.8–<11.1 mmol/Ltolerance

Impaired fasting ≥6.0 –<7.0 mmol/Lglucose

Normal <6.0 mmol/L

9

New aetiological classification of diabetes mellitus(American Diabetes Association, ADA 1997)

I. Type 1 diabetesβ-cell destruction, usually resulting in absolute insulindeficiencyA. immunologically mediatedB. idiopathic

II. Type 2 diabetesType 2 diabetes can range from marked insulinresistance with a relative insulin deficiency to markedsecretory impairment with insulin resistance.

III. Other specific typesA) Genetic defects of cell functionB) Genetic defects of the action of insulinC) Diseases of the exocrine pancreas, e.g. pancreatitis,

haemochromatosisD) Endocrinopathies, e.g. acromegaly, Cushing’s

syndromeE) Drug or chemical induced, e.g. glucocorticoidsF) InfectionsG) Rare immune-mediated forms, e.g. anti-insulin

receptor antibodiesH) Other genetic syndromes, e.g. Down’s Syndrome,

Klinefelter’s syndrome

IV. Gestational diabetes (GDM)

Treatment and self-monitoring of diabetes mellitus

The treatment of diabetes mellitus has the following aims:1. Prevention of acute metabolic disorders (hypo-

glycaemia, symptomatic hyperglycaemia, hyperosmo-lar and ketoacidotic diabetic coma)

2. The avoidance of diabetic complications, bothmicrovascular (retinopathy, nephropathy and neuro-pathy) and macrovascular (coronary heart disease,peripheral and cerebral arterial occlusive disease).

The incidence rate (rate of new occurrences) of diabeticketoacidosis is currently between 5 and 8 per 1,000patients annually1 and the related mortality well below1%. In the largest prospective study on the treatment oftype 2 diabetes (UKPDS, almost 4,000 patients, 15 yearobservation period) only one insulin-treated patientdied during an episode of hypoglycaemia6. Commen-surate with the origin of the disease, only insulin therapy

10

is available for the treatment of type1 diabetes. Adistinction is drawn here between conventional insulintherapy (CT) with the administration of long-acting ormixed insulin once to three times daily, and intensifiedconventional insulin therapy (ICT) on the basal bolusprinciple (covering basal requirements with administra-tion of long-acting insulin once to four times daily andan injection of normal (short-acting) insulin at mealtimesdepending on the quantity of carbohydrates ingested.The insulin analogue (“designer insulin”) Humalog® andNovo Rapid® (insulin lispro and insulin aspart) hasbeen available for this purpose since 1996. If basal andmealtime requirements are provided constantly via apump, then this is referred to as continuous subcut-aneous insulin infusion (CSII) or insulin pump therapy.

The success of treatment is measured by the proportionof glycosylated haemoglobin to total haemoglobin(HBA1c value). This value is maintained below 7% toprevent vascular diabetic complications in accordancewith the results of the DCCT study7 and the UKPDstudy6, corresponding to near-normoglycaemic bloodsugar control.

Since the end of the DCCT study in 19937, ICT has beenconsidered the gold standard in the treatment of type 1diabetics. Compared to conventional insulin therapy, theoccurrence or progression of vascular complicationshas been reduced by 50 to 70%. Similar reduction rateshave been published for an “intensive treatment” regimein type 2 diabetes. In obese patients, treatment withinsulin or oral antidiabetics (e.g. glibenclamide6, metfor-min8) is compared to less intensive (mainly dietary)therapy with less specific target criteria. In this case theearly institution of insulin therapy is frequently necessaryto achieve the desired HBA1c value. Self-monitoring bydiabetics nowadays goes well beyond the self-measure-ment of blood and urine glucose values:

1. Blood pressure self-monitoring2. Weight control3. Self-determination of protein elimination in the urine4. Regular foot inspections for diabetic ulcer.

Patient training and instruction to increase self-help(empowerment) is necessary as a further pillar ofdiabetes therapy and should no longer be withheld fromany diabetic.

11

Secondary complications of diabetes mellitus

Sustained hyperglycaemic blood sugar values are theunderlying pathological factor in the development ofsecondary diabetic complications. In type 1 diabetes, thediagnosis is established shortly after the onset of hyper-glycaemia and several years of inadequate metaboliccompensation are generally necessary for any secondarycomplication to become apparent. The onset of type 2diabetes often passes unnoticed and the disease can bediagnosed four to seven years too late9. During thisphase of undiagnosed diabetes mellitus, excessive bloodsugar values result in the development or progression ofmicrovascular (diabetic retinopathy, diabetic nephropathyand diabetic neuropathy) and macrovascular (coronaryheart disease, peripheral arterial occlusive disease,cerebral arterial occlusive disease) complications. Thesecomplications of diabetes are associated with certain lifehabits (sedentary lifestyle, smoking, alcohol) and otherdisorders of a metabolic (lipid metabolism disorders,obesity) and haemodynamic (hypertension) nature. Inasymptomatic patients with often only slightly raisedblood sugar values, doctors with insufficient experience indiabetology are reluctant to diagnose diabetes mellitusand to institute appropriate therapy at an early stage.

At the time of diagnosis, a cardiovascular complication orneuropathy is already present in about 10% of diabeticsand nephropathy or retinopathy in 20 to 30% of patients10.Forty percent of newly diagnosed diabetics in the UKPDstudy6 had arterial hypertension (in most cases untreat-ed). Inadequately treated hypertension is at least asimportant a risk factor as excessive blood sugar values,particularly for macrovascular complications but alsofor the progression of an existing diabetic nephropathy11.Combinations of microvascular disorders, i.e. retinopathyand neuropathy, and the formation of foot ulcers aredescribed at the time of diagnosis12. In the first four yearsfollowing diagnosis, about 20% of diabetics suffer fromperipheral diabetic neuropathy, which increases to 50%or more after 15 years. Diabetic retinopathy is found in20% of type 2 diabetic at the time of diagnosis. Again at15 years, a background retinopathy is found in 97% ofall type 1 diabetics and about 70% of type 2 diabetics.A proliferative retinopathy necessitating treatment is foundat this stage in 30% and 15% of patients, respectively1.

12

In the worst-case scenario, diabetic nephropathy canresult in terminal renal insufficiency and the need forhaemo dialysis in the early stages. In Germany no lessthan 35% of all dialysis patients in 1996 were diabetics,(more than 90% of them type 2 diabetics). With annualtreatment costs of about 40,000 EUR per dialysis patient,this complication alone generates direct treatmentcosts of more than 500 million EUR annually13. Peripheralarterial occlusive disease affects diabetics four to tentimes more often than non-diabetics, and the rate ofCVA is approximately threefold. Half of all deaths amongdiabetics are due to a cardiac disease1. Some informa-tion about the differing risk of micro- and macrovascularcomplications may be deduced from the patient familyhistory. Late diagnosis of diabetes and genetic pre-disposition appear to put an individual at increased riskof secondary microvascular lesions. Macrovascularproblems are more likely to occur in patients with lipidmetabolism disorders, obesity and an increasedincidence of hypertension in the family14.

Screening of risk groups for early detection of diabetesmellitus and subsequent treatment of hyperglycaemiaand hypertension are cost-effective15. It also reduces thecomplications of diabetes dramatically. Early diagnosisthen allows regular follow up examination of patients inorder to delay or prevent end organ damage (blindness,renal insufficiency, amputation), which incurs great coststo the health care system.

13

Definition and history of thediabetic foot syndromeThe concept of diabetic foot syndrome incorporatesvarious clinical pictures characterised by differentaetiologies and pathological mechanisms. Common to allis the fact that injuries to the foot of the diabetic patientcan result in complications that may lead to amputation ofthe whole limb if treatment is delayed or ineffective.

Pryce described “a case of a perforating ulcer in dia-betes and atactic symptoms” as early as 188716.In the first half of this century, foot lesions in diabetics,which frequently lead to amputation, were consideredan unavoidable complication of diabetes associated witharteriosclerosis and were classed under the headingof “diabetic gangrene”17.

In 1934, Elliot Joslin, one of the pioneers of diabetology,published an article entitled “The menace of diabeticgangrene”18. According to his observations, diabeticgangrene as a cause of death in diabetics had increasedfrom 2% before 1914 to more than 12% by 1926, only afew years after the discovery of insulin. Although impair-ed circulation and the consequent diabetic gangrenewas considered the main cause of diabetic foot compli-cations, Joslin described in detail the now well-knowncommon causes of diabetic foot lesions, i.e. burns fromhot water bottles, ill-fitting new shoes and lack of foothygiene. He vehemently advocated the intensive edu-cation of patients about cleanliness and care of their feetin order to minimise the occurrence of impending dia-betic gangrene. “Consequently it has been forced uponme”, he wrote, “that gangrene is not heaven-sent, butis earth-born”.

However, it was not until the 1950s that diabetic neuro-pathy, ischaemia and infection, were finally recognisedas precondition5 of foot complications in diabetics – factsthat still hold good today. The good prognosis for localsurgery in neuropathic lesions and the confinement ofradical surgical interventions to ischaemic changes wasalso described first at that time19.

The need for specialised care of diabetics with footproblems became increasingly apparent in subsequentyears and it was recognised that many approachesto treatment (pressure relief, shoe provision) could be

14

derived from the procedures adopted in another diseaseassociated with a neuropathic impairment of sensoryperception, leprosy20. In the 1970s, special programmesto improve the prognosis in diabetic foot complica-tions were introduced for the first time in Atlanta, USA.The amputation rate in diabetics was reduced by50%. Institutions with similar success rates were subse-quently set up in Europe, firstly in Geneva and London22,and then in Germany in 1983 (Prof. Ernst Chantelau,Dr. Maximilian Spraul and Prof. Michael Berger at the Uni-versity Hospital of Düsseldorf 23, 24). In 1989, the St.VincentDeclaration25 set a target of halving the amputationrate in diabetics within a five-year period. Subsequently,outpatient foot departments were created. In 1993these joined together to form an association, the DiabeticFoot Working Group, affiliated to the German DiabetesSociety.

Increasing interest in the diabetic foot was also reflectedin research activities. In the journals of the Americanand British Diabetes Societies the number of articles onsubjects related to diabetic foot syndrome in each casedoubled between 1982 and 1996, while at the AmericanDiabetes Congress, three times as many contributionsdealt with the subject in 1996 as in 1980. Since 1998,a medical journal “The Diabetic Foot,” published fourtimes a year in England, has been devoted to the sub-ject. International meetings on the topic of diabeticfoot problems lasting several days are held annually inSan Antonio (Texas, USA) and every two years inMalvern (England). An international symposium wasorganised on the diabetic foot for the first time in1991 in the Netherlands, attended by 500 participantsfrom 46 countries. The third and most recent was heldin May 199926.

15

Diabetes treatment and research in Europe:The St. Vincent Declaration (1989)

Five-year aims of the St. Vincent Declaration:

– Implementation of effective measures forprevention of costly complications

– Reduction of the rate of new cases of blindnessdue to diabetes by one third or more

– Reduction of the numbers of people entering end-stage diabetic renal failure by at least one third

– Reduction by one half in the rate of limbamputations for diabetic gangrene

– Cut morbidity and mortality from coronary heartdisease in the diabetic by vigorous programmes ofrisk factor reduction

– Achieve pregnancy outcome in the diabeticwoman that approximates to that of the non-diabetic woman

Despite all these activities, the care of patients with dia-betic foot problems in Germany has still not beensatisfactorily resolved, and further urgent improvementsare required.

16

Epidemiology of thediabetic foot syndrome

A quarter of the diabetic population is at increasedrisk of foot injuries as a result of the presence of dia-betic neuropathy or an arterial circulatory disorder.Every year 3 to 7% of diabetics suffer a foot lesion forthe first time. Following healing of the injury, the riskof suffering a further ulceration (relapse) increasesannually to between 30 and 100%, depending on thequality of the after-care. Like previous amputees,these patients must also be regarded as high-riskpatients and require very intensive, structured moni-toring and care. In Germany, more than 20,000 footlesions in diabetics still culminate in amputation peryear. Following an amputation, mortality is approxi-mately 20%. Within 3 years 50% of the survivingpatients also undergo an amputation on the contra-lateral side. The five year survival of patients afteramputation is low, approximating 25%.

More than four million diabetics are known to be living inGermany today27. If patients at risk of diabetic footcomplications are defined as those diabetics who sufferfrom diabetic neuropathy and/or in whom two or morefoot pulses cannot be felt, then 25% of the diabeticpopulation belong to this risk group28. In the case ofGermany, this yields an estimated 1.25 million diabeticpatients at risk of lesions of the lower limb. The mostnegative consequence of such an injury, amputation,affects diabetics of various age groups up to 100 timesmore frequently than their non-diabetic peers29.

17

Sensorimotor and autonomic diabetic neuropathy andperipheral arterial occlusive disease must be regardedas the most common underlying conditions for diabeticfoot complications. These can lead to foot injuries indiabetics either alone or in combination. In 600 Englishpatients with ulceration, neuropathy was found to bethe cause in 45%. Fortyfive percent of these patients ex-hibited both diabetic neuropathy and a circulatory dis-order, and only 7% suffered exclusively from a peripheralcirculatory disorder. In aetiological terms, neuropathyproved to be responsible for 90% of injuries30. In 260 ofour own patients with foot injuries, neuropathy was foundin 80% of cases, and of these 43% had accompanyingcirculatory disorders. As in the British study30, an isolatedarterial occlusive disease occurred in only 10% ofpatients.

Diabetic neuropathy must therefore be seen as a pre-disposing factor to diabetic foot lesions. This may be dueto external (e.g. ill-fitting footware) or internal pressure(limited joint mobility) foot deformities and severe footpressure. Increased foot pressure is to be found in 20%of patients even without a clinically detectable neuro-pathy and can be used to identify patients at risk ofulceration. Almost 30% of patients with increased footpressure suffer from ulceration during the following twoyears30. The incidence of symptomatic diabetic neuro-pathy varies with the patient’s age and the duration ofdiabetes: 5% of diabetics aged between 20 and 29 yearsexhibited neuropathy. This rises to 40% between theages of 70 and 79 years. At the time of diagnosis, 7% ofpatients in the UKPD study5 were suffering from neuro-pathy. Five years after diagnosis, 20% of the patientshad detectable neuropathy and this figure increased toapproximately 45% with the longer duration of thedisease (40 years or more)31,32.

Diabetic neuropathy was found in half the type 2 dia-betics aged over 60 years. Although the lack of pain frominjuries predisposes to the development of diabeticfoot complications, pain in the lower extremity does not inany way preclude neuropathy (“painful-painless leg”).Veves found a painful neuropathy of this nature in almosthalf of neuropathic patients and a third of patients withfoot ulcer33.

18

Among non-selected patients in general practice,an arterial occlusive disease is found in about a third ofdiabetics, about four times as often as non-diabetics34.

Preliminary signs of ulcer disease (prelesions suchas a hard callus with or without maceration) are detectedin approximately one in seven patients with an existingdiabetic neuropathy. In these patients, the developmentof a perforating ulcer of the foot (classic neuropathicpressure ulcer) can be avoided with adequate and earlytreatment35. In a regional study in Rhineland-Palatinate,hyperkeratosis was found in almost 70% of patients, ofwhom half showed additional subcallosal suggillations.In this study involving almost 900 patients, 8% exhibiteda florid, open foot lesion, and almost 15% of thosestudied reported a previous history of such lesions36.

When a lesion of this kind is healed, there is still a lifelongrisk of recurrence of the ulcer because of the ongoingunderlying disease. In a large Swedish study recurrentulceration was found in 34%, 61% and 70% of ulcerpatients after 1, 3 and 5 years, respectively. Fifty percenthad suffered another lesion within two years37.

Foot ulceration is the most frequent cause of amputationsin diabetics38. The risk of an amputation of a limbvaries according to the patient’s age, race and sex39, 40, 41.Common to all, however, is the fact that the risk of under-going an amputation is 20 to 40 times higher (in someage groups up to 100-fold) than in comparable non-diabetics39,42,43. However, the idea that a limb amputationis an event that occurs late in the course of diabetesis incorrect. According to an English study, 20% ofamputations occur in the year in which the diabetes isdiagnosed44. The level of amputation is particularlyimportant for a later independent lifestyle and theprognosis of the patient. After amputations of the toesand forefoot (minor amputations) between 5% and7% require permanent care, whereas in the case of majoramputations (lower and upper limb) 36% require per-manent care.

19

The probability of survival and the risk of an amputationon the opposite side are also closely correlated tothe amputation level. Mortality after two amputations isapproximately 3%, whereas this figure rises to 20%after major amputation45. The 5 year survival rate afteramputation is 27% which compares to 60% of patientswhose foot lesion is healed with conservative treatment37.The probability of a limb amputation on the oppositeside following a successful major amputation is 12% inthe first year and more than 50% after three years.

If the aim of reducing amputation by half is to beachieved, the diabetic patient must be advised to avoidany situation that might result in foot ulceration.

20

Socio-economicsignificance of the diabeticfoot syndromeCosts due to foot complications in diabetics

When talking about medical topics, it is not possible toignore the associated costs. Few data are availableon the costs resulting from diabetic foot syndrome in Ger-many, but the extent of the problem can be illustratedusing data from Scandinavia, Great Britain and the USA.Overall, the costs generated by diabetes are aboutthree times as high as those produced by non-dia-betics46. Foot complications constitute a major proportionof these: every fifth hospital admission for diabetics isa result of foot problems. As the inpatient period can beprolonged, foot complications are responsible for almosthalf of all inpatient days for diabetics47. In Great Britain,hospitalisation as a result of diabetic foot complicationsalone results in annual costs equivalent to 375 millionEUR. Inpatient treatment costs are the most significantsingle factor. With primary healing, about 30% of the to-tal cost derives from hospitalisation, but where amputa-tion is required this figure is 65% to 80%48,49. The averagehealing duration for diabetic foot lesions is about fourmonths. Ten percent of all lesions persist for more thanone year, which incurs further costs for outpatient care.Fifteen percent of all foot ulcers in diabetics do not healbefore the patient’s death49.

Beside the long period of inpatient care that is frequentlyrequired, the high likelihood of an amputation and therisk of life-long disability are important cost-generatingfactors48. The average costs of a superficial diabeticfoot ulcer are estimated at approximately 4,500 EUR. Inthe presence of a deep infection this increases to 23,500EUR and with the occurrence of gangrene may riseto 50,000 EUR. In the case of primary healing, expensesamounting to some 7,500 EUR are incurred, but thiscould be multiplied sixfold where an amputation is re-quired.

21

The costs of antibiotic treatment (less than 1% of theoverall costs) or technical orthopaedic measures (about3% in the case of primary healing) are relatively small50.The costs of local wound treatment are less determinedby the use of certain wound dressings, but to a muchgreater extent by the frequency with which bandages arechanged.

When calculating the actual financial burden resultingfrom diabetic foot problems, it is essential to take along-term view. The potential risk of recurrent ulceration,amputation or the patient’s death must be incorporatedin the calculations. Over a 3-year period, a primarily heal-ing neuropathic ulcer incurs costs of about 15,000 EURoverall51. With a conservatively healed ischaemic lesion,the costs rise to about 25,000 EUR. If amputation of anextremity is necessary, in the following three years onaverage about 40,000 EUR annually are required simplyfor domestic care. In the USA, the direct costs of anamputation are put at 15,000 to 50,000 EUR dependingon the amputation level required52. If the indirect costsresulting from loss of productivity are added to this, thefigure is more than doubled53. A recent American studycalculated the annual total costs resulting from diabeticfoot problems in the United States to be 5,000 millionEUR54.

As outlined earlier, the diabetic foot syndrome incursmassive financial costs to the health services and thepatient. Just as impressive as the costs incurred, are thecalculations of the potential savings that can be madefrom preventive strategies in the treatment of the diabeticfoot syndrome. In the USA in 1998 the annual savingsresulting from the avoidance of amputations as a result ofstructured patient information was estimated at 3 to4,500 EUR per patient52. Calculations by Assal in Genevasuggest that for every dollar invested in educatingdiabetics, savings of three to four times that amount maybe expected. Savings made as a result of avoidingnine limb amputations could finance the treatment of 400diabetic patients for a year, 820 hours of group training,further 1,100 hours of individual training for diabetics andan additional 1,500 foot visits55.

One cost item, however, does not feature in any of thesecalculations, namely the ”cost“ to the patient themselvesin terms of the emotional trauma suffered and the loss ofquality of life and independence.

22

Psychological aspects and effect on quality of life

“Quality of life is a descriptive concept that is intended toprovide information about the degree of satisfaction withlife or those factors which make life worth living” (from:J.M. Last: A Dictionary of Epidemiology). In medicine,the concept involves three dimensions:

1. Physical capacity2. Subjective well-being3. The individual’s social relations with his environment

Since purely objective findings are insufficient for asses-sing the quality of life, the patient’s subjective well-beingand his own assessment of his condition increasinglyneed to be included in the medical evaluation and givendue consideration in the treatment of a disease56.

Logically, the effect of diabetic foot injuries on thequality of life of both the patient and their relatives shouldbe considered jointly. The few studies that have beenpublished to date on this subject are unanimous: thedecisive factor that affects the quality of life of patientswith diabetic foot problems is the restriction on theirmobility. This adversely affects their social situation andcan result in various psychological responses57,58.

One example of this is the fact that patients whoare mobile after amputation rate their quality of life morehighly than patients with florid foot lesions59. The restric-tion on the sphere of activity impinges on the patient’soccupational and social situation and can lead to feel-ings such as guilt (“being a burden on others”). Theresultant anger and frustration (loss of independence)are associated with fear and worry (“How long will this goon for?”, “Will it result in amputation?”)57. Relativeson the one hand become the target for the patient’s un-happiness and imballance and on the other handhave to assume new roles in the patient’s life (transport tomedical appointments, taking over everyday activitiespreviously undertaken by the patient themselves).Opportunities for social contacts and the scope formovement (e.g. travel and holidays) are equally limitedfor patient and relatives.

23

Tension in relationships is therefore unavoidable.A few sufferers, however, regard the more intensive cont-act with their relatives, even if involuntary, as a positivefactor and acquire more patience in dealing with othereveryday problems as a result of handling this parti-cular situation. The ability to cope with these changes isinfluenced by the patient’s age and social origins58.Among younger patients, the anxiety of losing one’s job,impending financial losses and the reduction in selfes-teem take precedence. Elderly sufferers rate socialisolation as more serious. Physical effects on the qualityof life are elicited in the form of side effects to any anti-biotic treatment required and the tiredness and exhaus-tion that result from the increased expenditure of energyneeded for moving about57.

Fear of the consequences of foot ulceration can channelthe patient’s behaviour in various directions: a depressivemood or paranoia-like fixation on the foot injury mayresult. Equally there may be total denial of the situation,associated with non-attendance at outpatient appoint-ments or failure to attend in the event of new injuries60.It is at this point that the diabetic foot team can providetargeted, patient-oriented information about the diseaseand avoidance of unrealistic expectations on the partof the patient. This effort of the team, together with theprovision of therapeutic certainty are important basesfor the successful treatment of patients with foot lesions.Disappointment and failure can thus be minimised,avoiding the incorrect behaviour pattern in patients.

Psychological problems affect the clinical course andthe subsequent outcome of treatment of patients withdiabetic foot complications. Members of treatmentteams should be aware of such stresses on the patient-therapist relationship, be willing to review treatment,and, if necessary, change their own patterns of behavi-our and expectations in this respect.

24

Reduced sweat gland activity,loss of the plantar fat padand impaired joint mobility indiabetic neuropathy, to-gether with the resultant callusformation, lead to callushaematomas at exposed sitesif the pressure is not relieved

Risk factors for footcomplications in diabetics

The main risk conditions for the occurrence of footlesions in diabetics are the loss of protectivemechanisms in the presence of a diabetic neuropathyand the absence of sufficient tissue perfusionas a result of an arterial occlusive disease (AOD).

The most important risk factors are:Bony foot deformities, the existence of increasedplantar pressure, impairment of vision and mobilityand a previous history of a diabetic foot lesion.Infections play a minor role in the genesis of a dia-betic foot lesion, but assume considerableimportance in existing injuries as a risk factor forprogression to amputation.

One of the most effective means of preventing diabeticfoot complications is a regular foot examination aswell as the identification of risk indicators. Unfortunately,foot examinations in diabetics are only rarely performed.And when they are performed – in both outpatientand inpatient settings – then they are often inadequate.A thorough foot status is established in only about 10%of all diabetics during routine outpatient visits. Evenamong patients who are admitted to hospital for a dia-betic foot ulcer only 14% are adequately examined interms of their foot findings61.

25

The following section begins by presenting the differentrisk factors for foot lesions which may lead to amputationsin diabetics and their importance, before going on toinvestigate in detail the causative factors of foot injuries.

Although different authors ascribe different significancein their studies to the various risk factors for diabeticfoot lesions, the same basic risk factors are implicated:

1. Peripheral neuropathy2. Bony foot deformities3. Existence of increased plantar pressure4. History of ulcer5. Peripheral arterial occlusive disease.

Peripheral sensorimotor neuropathy represents the mostimportant risk factor for the occurrence of foot ulcera-tions and amputation in diabetics. Patients rarely developa diabetic foot ulcer in the absence of neuropathy. Theloss of the protective perception of pain and pressureis the underlying cause of foot complications in diabetics.The occurrence of a foot ulcer in the great majority ofcases is a multifactorial and complex process in whichvarious risk factors play a role. Neuropathy is found as asubsidiary factor in about 90% of cases62. The risk ofsuffering ulceration of the foot increases ten-fold in thepresence of signs of diabetic neuropathy (detected bythe pathological monofilament test and pathologicalvibration sensation in the biothesiometer test) comparedwith neurologically healthy diabetics63.

In addition to the reduced awareness of injury resultingfrom the impairment of the sensory nerve fibres, two othermajor risk factors are involved:

1. The occurrence of bony deformities of the foot2. Increased plantar pressure

These factors also lead to atrophy of the small musclesof the foot with the consequent impairment of balance.The impairment of autonomic nerve fibres leads to afailure of sweat gland function and consequently to lossof skin elasticity.

26

Foot deformities, together with severe hyperkeratosis(callus formation) contribute to foot ulceration in about60% of cases, and increased plantar pressure in 50%.Reduced adaptability and increased pressure loadsarise through a variety of mechanisms: changes in theskin and peri-articular structures (e.g. joint capsules)result in an impairment of joint mobility64. The resultantincrease of approximately 30% in foot pressure values,combined with the loss of protection due to neuropathy,considerably increases the risk of an ulcer formation.

Typical localisation of footinjuries as a result of narrowfootware or hard toecaps

Poor foot care in a 90-year olddiabetic resulting in deformedonychomycotic toenails,excessive callus formation onthe soles of the feet andsubcallus haematomas on thefirst and second toes

27

Ischaemic diabetic footsyndrome with pressurenecrosis on the sides of thefoot and toes, associatedwith dry gangrene of the thirdtoe

This is supported by studies of rheumatoid arthritispatients with foot deformities, but without concurrentneuropathy65. More recent studies indicate hardening ofthe peri-articular connective tissue and increasingatrophy and fibrosis of the plantar fat pad as indepen-dent risk factors, particularly in recurrent lesions66,67.Such changes are found in the presence of even mildneuropathy, but their intensity increases proportionatelyto the severity of underlying the neuropathic disease.An effect on the capillary blood flow as a result of theincreased plantar pressure load and increased fibrosisas a result of a chronic inflammatory irritation are sug-gested as possible pathological causes. Fibrosis andatrophy of the plantar fat pad affect the biomechanicalproperties of the sole of foot in the same way as thefrequently observed increased callus formation. Removalof the callus reduces the pressure load on the soleof the foot by about 25% and hence reduces the risk ofsubcallous haematoma, as well as subsequent ulcerformation68.

Finally, patients with a previous history of diabetic footulcer are at highest-risk of relapse, because of theconstant risk conditions and the structural foot changesdescribed (less resistant and less flexible tissue orchange in the pressure-bearing surface following minorsurgery). The risk of suffering a relapse is tripledfollowing primary ulcer healing69 and increases to about50-fold following surgical treatment70.

28

Ischaemia as a consequence of peripheral arterialocclusive disease represents a minor contributory factorto the occurrence of diabetic ulcer (23 to 35%62,71),but assumes increasing significance as a risk factor inthe progression of a foot ulcer towards amputation38.Critical limb ischaemia (CLI) is present in 50% of alldiabetic foot lesions that end in amputation. Whereasulcer formation is a multifactorial process, ischaemiain itself can be sufficient to result in amputation.

While peripheral arterial occlusive disease in non-dia-betics is the reason for amputation in the majority ofcases, several factors are usually involved in diabetics,both in the occurrence of an ulcer and also in the sub-sequent progression to amputation. In 80% of cases,there is an identifiable, acute cause, mainly footwear-related or thermal trauma (burn, excessive cold). Subse-quent ulceration and insufficient wound healingcontribute to the amputation of all or part of a limb38.Peripheral oedema (40%), ignorance about foot care(25%) and lack of social integration (20%) are furtherfactors leading to amputation.

In 80% of cases the initial insult that results in ulcer for-mation and ultimately amputation can be identified 38,62,72,a fact that appears extremely important in relation to theadvice given to patients in order to prevent recurrance.

Infection plays a minor role in the causation of diabeticfoot lesions (less than 1% of cases71), but is a majorrisk factor for amputation (involved in 60% of cases)38.What is important here in diabetics is the frequent ab-sence of the classic signs of infection (fever, leuco-cytosis, increased erythrocyte sedimentation rate, [ESR])because of the existing immunopathy73. Despite multi-disciplinary care, surgery is unavoidable in almost 90%of diabetics with deep foot infections. In 34% of casesthis involves minor amputations and in 10% a high-levellimb amputation.

29

The probability of a major amputation is increased by thepresence of:

1. Pain (the relative risk increases 13-fold)2. Progressive gangrene (14-fold)3. Pre-existing intermittent claudication (6-fold).

None of these signs, however, precludes primary heal-ing or healing following minor surgery74. The risk ofhaving to undergo an amputation is also increased in thepresence of an additional cardiovascular disease, dia-betic neuropathy, reduced arterial ankle pressure (lessthan 80 mmHg) or toe pressure (less than 45 mmHg).Male patients74 are also at higher risk. A further importantrisk factor for the occurrence of foot ulceration is impair-ed vision and reduced mobility, as these factors limitthe patient’s ability to co-operate in foot inspections andfoot care. Eighty percent of sufferers are totally unawareof this restriction. In a study by Assal, impaired visionwas found in 70% of diabetic ulcer patients studied, 10%of the patients with neuropathy but no ulceration, andonly 5% of non-neuropathic diabetics.

Inadequate visual acuity (defined as patient‘s in-capability to observe a lesion of 3 mm in diameter at theminimum eye-foot distance) was found in 50%, 5%and 3% of patients, respectively75. Impaired vision alsoconstitutes an independent risk factor for fractureswith the subsequent formation of Charcot’s deformity asa result of the increased risk of spraining and tripping76.

In a large Italian case-control study possible risk factorsfor ulcer formation were77:1. Male sex (the relative risk increases 3-fold)2. Lack of family involvement (1.4-fold)3. Difficulty attending follow up appointments (2-fold)4. Lack of diabetes education (3-fold)5. Irregular compliance with foot inspections.

30

In central Europe, the occurrence of diabetic footulcerations is preceded in 28%78 to 55%79 of casesby shoe-related injuries. Eighteen percent are the conse-quence of injuries related to foot care, while 3% arepreceded by other minor trauma. Thermal traumas, parti-cularly burns, are relatively rare (2% of all cases), butare significant because of the risk of hypertrophic scarformation and delayed recovery. At temperatures of44°C, a theoretical exposure of six hours is required fornecrosis formation, whereas at a temperature of 50°C,only a five-minute exposure is sufficient80. In diabetics, adisorder of hot and cold perception is found in the handsas well as in the lower limb. In other regions of the world,causes of diabetic foot injuries include rat bites81, worminfestations82 or burn injuries from the use of alternativemedical methods such as moxibustion, a traditionalChinese medical procedure83.

As previously, mentioned certain constantly recurringsets of circumstances can result in foot ulcerations71

and amputations38. An understanding of these facts isessential for the successful employment of preventativestrategies. A distinction is drawn here between contri-butory factors which, together, might result in the event(ulcer or amputation), and “sufficient causes” which canproduce such an event in themselves. The causal factorcan be found in 80% of ulcers and 86% of amputations.

31

Three frequent pathways, which together account for60% of all ulcers, are:

1. Neuropathy, deformity, callus formation, increasedpressure

2. Penetrating minor trauma3. Ill-fitting shoes61

The combination of minor trauma, skin ulceration anddelayed wound healing with or without the co-existenceof infection or gangrene results in amputation in 70%of cases. Eighty-four percent of all amputations are pre-ceded by ulcer formation38.

Diabetic foot ulcerations are a significant problembecause:

1. They are very common2. They are cost-intensive3. They can identify patients at risk of amputation4. They adversely affect the functional status and well-

being of the patient concerned5. They can be avoided in many patients by

preventive foot care and the use of specificallydesigned footwear84

Early identification of the risk factors and appropriateimplementation of preventive and therapeutic measureswould dramatically reduce the occurrence of footcomplications and their consequences in diabetics.

32

Concurrent diseasesin diabetics withfoot complicationsThe average age of diabetics with foot injuries ismore than 65 years85,86. Mediocre response to treatmentin these patients is due in part to the multimorbidityof sufferers. Patients with foot lesions suffer to a consider-able extent from macrovascular disease and the con-sequences of diabetic microangiopathy. Diabetic retino-pathy, autonomic diabetic neuropathy and diabeticnephropathy are more frequently found in type 1 dia-betics than in type 2 diabetics with foot lesions, whohave a greater incidence of coronary vessel disease andperipheral arterial occlusive disease (PAOD)85. In 243patients from the Dortmund Hospital, neuropathy wasfound in 80% of ulcer patients. Nephropathy, retinopathyand coronary heart disease were found in 50% ofpatients. Involvement of the arteries supplying the brainin 22% and PAOD in almost 70%87. Similar figureswere obtained in our own patient population: neuropathy80%, nephropathy 65%, retinopathy 55%, myocardialinfarct 19%, stroke 20% and PAOD 56%.

The risk of a concurrent disease of the coronary vesselsin patients suffering from PAOD is increased two and ahalf times compared with patients without disease of theleg vessels. The disease is frequently asymptomatic,particularly in women88. Prognostically, the occurrence ofgangrene of the toe in particular may be consideredan extremely adverse sign in terms of patient survivalrate. The mean survival time of these patients followingthe onset of gangrene is on average less than 18 months.In the study quoted, smokers (82% smokers vs. 45%non smokers) and patients requiring an amputation (64%amputated vs. 27% non amputated) were found signi-ficantly more often among patients who died early thanamong those with a more favourable prognosis forsurvival86.

There is an obvious relationship between increasedprotein loss from the kidney (micro-albuminuria, protein-uria) and the occurrence of ulcers in diabetics. Althoughthe abnormal excretion of albumin from the kidney intype 2 diabetics is of renal origin, it reflects a vascularprocess that involves the nephron and the tunica intimaof the large vessels. Micro-albuminuria is therefore,

33

a marker of a progressive renal disease and a predictorof a generalised arteriosclerosis and early death89.Increased albumin excretion occurs most frequently inpatients with ischaemic and neuro-ischaemic lesions.It is also found to a greater extent in patients with purelyneuropathic ulcers, as compared to ulcer-freediabetics90.

Diabetic retinopathy is an important finding in footpatients for several reasons. Firstly it represents a riskfactor for the development of foot injuries (see alsochapter “Risk factors for foot complications in diabetics”).Secondly, the concurrent presence of the two

diseases is increasingly found at the time of diagnosis intype 2 diabetics11. If an arterial occlusive disease ispresent at the time of diagnosis, then the survival rate inthese patients is markedly reduced. After five yearsless than 20% survive91. The occurrence of both diseasestates at the time of diagnosis of type 2 diabetes isparticularly common among smokers.

Typical fundoscopicfindings in proliferative dia-betic retinopathy:diabetic retinopathy is con-sidered a risk factor forfoot complications becauseof the impairment of vision

34

The high incidence of concurrent micro- and macro-vascular disease in patients with foot ulcers showsthe urgent need for the use of all available options forearly diagnosis and appropriate treatment, not onlyto increase the chances of a positive outcome of the footlesion, but also to have a beneficial effect on the overallfate of the patient affected.

35

Diagnosis and differentialdiagnosis of the diabetic footsyndromeDiagnosis of sensorimotor and autonomicdiabetic neuropathy and diabetic neuropathicosteoarthropathy

The human nervous system consists of the peripheralnervous system (PNS) and the central nervous system(CNS). The CNS comprises the brain and the spinalcord. The somatic and autonomic nervous systems aredistinguished in terms of their functions. Somatic nervefibres conduct stimuli to the muscles and converselyfrom the sensory receptors to the CNS. Neurons thatare not subject to voluntary control are grouped togetherunder the heading of the autonomic nervous system.In the lower limb, they exert a particular action on the re-gulation of vascular tone and the secretion of sweatglands. Neuropathies are characterised by a progressiveloss of nerve fibres, which can be detected by non-invasive tests of nerve function. The early identificationand education of patients with a loss of sensory percep-tion in the lower limb would be the most effective wayof avoiding foot injuries and amputations in diabetics.

The NEURODIAB Working Group of the EuropeanAssociation for the Study of Diabetes (EASD) agreedguidelines in 1998 for the annual follow-up of diabeticswith regard to their neurological status92. As opposedto the consensus guidelines of the San Antonio con-ference93, only simple and universally available investiga-tions, in addition to clinical examination, were pro-posed to establish nerve function. Diabetic neuropathy isdefined as “the presence of signs or symptoms ofperipheral nerve function disorders in diabetics followingthe exclusion of other causes”90.

Three sensory modalities can be easily tested:1. Vibration sensitivity (tuning fork test94 and

biothesiometry95)2. Pressure perception (Semmes-Weinstein

monofilaments96)3. Temperature discrimination (Tip Therm97)

36

Findings in neuropathicdiabetic foot syndrome withclaw toe deformity as a resultof shortening of the smallmuscles of the foot (aconsequence of motorneuropathy) and degenerationof the plantar aponeurosis

These tests provide information about the degree ofneuropathy and hence the risk of diabetics developingfoot lesions.

Disorders of autonomic innervation of the foot may besuspected in the presence of dry, cracked skin, fissuresand hyperkeratosis. The acetylcholine test (“sweat spottest”) is a suitable test method98. Electrophysiologicalinvestigations (e.g. nerve conduction velocity) serve moreto differentiate neuropathies of different aetiology thanto provide additional findings in diabetic foot syndrome.These tests do not add to the diagnostic value of themethods described above. Abnormalities of nerve con-duction velocities, moreover, are not consistent withthe clinical signs in diabetic neuropathy99.

Two clinical methods have become increasingly acceptedin Germany: the examination of vibration sensitivity withthe calibrated Rydel-Seiffer tuning fork and the recordingof pressure sensitivity with the 5.07 Semmes-Weinsteinmonofilament (10 gram application force).

Of the various manifestations of diabetic neuropathy,three are of relevance to the lower limb100: the acutesensory, chronic sensomotoric and autonomic neuro-pathies. A progressive, stocking-shaped, predominantlysymmetrical loss of vibration, temperature and painperception is typical of the chronic sensorimotor form ofthe disease. A lack of proprioceptive reflexes and

37

atrophy of the small foot muscles with a claw toeposition and prominent metatarsal bones may be consi-dered signs of involvement of motor nerve fibres.

The progressive glycosylation of the plantar aponeurosiswith an increasing loss of elasticity and an eventualrupture may contribute to these deformities101.

Autonomic nerve fibres are involved in a large numberof cases in patients with foot ulcerations102. Particularly inpatients with a diabetic neuropathic osteoarthropathy(DNOAP), involvement of the autonomic nervous systemis observed in more than 90% of cases103. Severe acuteand isolated autonomic neuropathies are rare mani-festations99. About two-thirds of diabetic neuropathieswhich follow are asymptomatic. Hence, the absenceof symptoms does not necessarily mean that the patienthas healthy feet100.

Loss of vibration sensation is the most common and ear-liest sign that nerve fibres are affected in diabeticneuropathy. Normal ageing has an effect on vibrationsensation, so have patient co-operation and motivation.Its usefulness in elderly patients is doubtful104. In addi-tion, proprioceptive reflexes cannot be detected inabout 70% of all elderly patients (including non-diabeticpatients).

The 128 Hz tuning fork is marked with a scale that issubdivided into eighths. An impairment of age-relatedimpairment of sensation was found in 20 of 26 patientswith foot ulcerations in a tuning fork test. A reductionto less than 4/8 occurred in 95% of ulcer patients105.In another study, a reduction in vibration sensitivity to 2/8or less was found in all patients with foot lesions94.The semiquantitative measurement of the vibration senseyields valuable information for patients under 60 yearsof age. Evaluation of the quantitative vibration measure-ment (determination of the vibration threshold) by bio-thesiometer yielded a threshold of normal sensation of25 V (volt). The risk of ulceration in the group of patientswith a sensitivity of between 25 and 33 V was increasedeight-fold, while with values of more than 42 V it increas-ed more than twenty-fold95.

While the vibration sensation test is used in screening forneuropathy, it is the loss of temperature discriminationand pain perception that is responsible for foot injuries indiabetics. The test of pressure sensitivity with the 5.07(10 gram) nylon filament is superior to the biothesiometer

38

measurement because of its higher sensitivity (100% vs.79%). Nylon filaments with a standardised applicationforce (1, 10 and 75 gram) are applied at specific pointson the patiants foot, bent and their perception tested96.

Temperature discrimination can be tested simply, eco-nomically and reproducibly with the Tip Therm (Axon,Düsseldorf). This is an instrument similar to a thick pencilwith a plastic side and a steel side. All 26 patients witha previous determined temperature discrimination thres-hold of less than 10 °C recognised the different tempera-ture on the two sides of the Tip Therm. In contrast, 20 of24 patients with impaired temperature perception (thres-hold greater than 10°C) were incapable of doing so97.With a combination of the tuning fork test, the monofila-ment test and the temperature discrimination (Tip Therm),the neurological risk status of each diabetic can there-fore be determined rapidly and cheaply.

A rare but important complication of diabetic neuropathyis diabetic neuropathic osteoarthropathy (DNOAP) whichis found in at least 0.1 to 0.5% of all diabetics. Cavanaghet al. (1994) even found evidence of osteoarthropathyin about 10% of all patients with diabetic neuropathy106,i.e. in about 3% of all diabetics.

Such changes were first described by Musgrave, 1703,as a consequence of sexual transmitted diseases107.In 1868, Charcot, after whom the final stage of osteo-arthropathy with marked deformities was also named,described painless neuropathic joint changes and bonedestruction in patients with tabes dorsalis108. Diabetesmellitus is the most common disease underlying suchchanges today. Such findings also occur in patients withleprosy, syringomyelia, in alcoholics and in patients withcongenital insensitivity to pain. The exact pathogeneticbackground of DNOAP has yet to be fully elucidated107.In the current state of knowledge, the autonomic neuro-pathy observed in almost all patients with diabeticosteoarthropathy results in increased blood flow as aresult of arteriovenous shunts, and ultimately in osteo-penia. The reduced bone density can often be detectedeven before the clinical onset of the disease109.

39

Acute diabetic osteoarthro-pathy with swelling, rednessand excessive heat andincipient deformity of the rightfoot.

The muscular imbalance caused by the presence of amotor neuropathy and the potential for concurrenttraumas due to the sensory deficit, result in repeatedperi-articular fractures with impaired healing andthe possible end-state of a severely deformed foot107.In addition to the swelling and redness of the affectedextremity, a temperature difference of more than 2°Cfrom the opposite side is indicative of an active osteo-arthropathy109.

According to Sanders, five forms of diabetic osteoarthro-pathy may be distinguished on the basis of their differentlocalisations110. Forms I, II and III involving the anteriorand middle parts of the foot constitute more than 80% ofall cases. Sella distinguishes four disease stages108.The intention here must be to identify this clinical picturedespite its relative rarity and to prevent extensive footdeformities through early diagnosis (clinical features,X-rays, CT scans) and the resultant appropriate relief ofpressure. In addition to this, initial findings from adjuvanttherapy with bisphosphanates provide promisingresults111.

40

Diagnosis of arterial occlusive disease

The most significant single factor affecting the riskof amputation for diabetics is ischaemia of the affectedextremities following an arterial occlusive disease. Ina large proportion of cases, degenerative arterioscleroticvessel processes underlie arterial circulatory disorders,resulting in a loss of elasticity of the vessel and ultimatelyocclusion of the lumen. Appropriate and early diagnosisof circulatory disorders and an understanding of thespecific features of the disease in diabetics areessential to avoid unnecessary amputations.

The prevalence of arterial circulatory disorders inGermany in the 55- to 64-year-old age group is about10%112. This rises to 21% in type 2 diabetics113. Otherrisk factors include the patient’s age, hypertension andheavy smoking. Although the incidence of peripheralarterial occlusive diseases (PAOD) is increased in diabe-tics and the disease manifests itself at an early age, the disease course is similar to that in non-diabetics114.

The misconception of an occlusive microangiopathy,the pitfalls of instrumental diagnosis in the presence ofMönckeberg’s arterial sclerosis and its significance forthe particular pattern of distribution of PAOD in diabeticsare presented below in further detail. This is followedby a description of the clinical features in the presence ofan associated sensorimotor diabetic neuropathy, to-gether with a step by step procedure for the diagnosis ofarterial occlusive disease.

The primary task in assessing diabetic foot lesions isthe differentiation of neuropathic and (neuro-)ischaemicfindings. The underlying difference between the twoforms is the existence (or absence) of foot pulses. Themost important basic diagnostic measure is thereforethe palpation of foot pulses. Doppler examination of theperipheral arteries using an occlusive pressure measure-ment (determination of the ankle-arm index of arterialblood pressure)115 and, where necessary, an oscillo-graphic examination or hydrostatic toe pressure measure-ment116,117,118 in the presence of media calcification arenon-invasive examinations that yield further information.

41

Clinical and instrumental diagnosis in diabetic foot syndrome

Neuropathic status Arterial vascular status

Previous history:Duration of diabetesClinical symptoms of neuropathy(“positive symptoms” such as nocturnalor resting pain, “negative symptoms”such as impaired or absence ofsensitivity to vibration, pain, pressure,temperature or touch) microvasculardiseases of the eye and kidneys, plusalcohol abuse

Inspection:Warm, dry, cracked skinAtrophy of the internal musculature ofthe foot with foot deformitiesHyperkeratosis and subcallushaematomas

Examinations:Reflex test (ATR)Vibration perception (Rydell-SeifferTuning fork, biothesiometer)Semmes-Weinstein monofilament (10 g)Temperature perception (Tip-Therm)

Previous history:Clinical signs of an arterial occlusivedisease such as resting pain or inter-mittent claudication (pain on exercise –both of which are often undetectablewhen a neuropathy is present simultan-eously)Vascular risk factors such as hyperten-sion, smoking, obesity and lipid meta-bolism disorders

Inspection:Cool, pale or livid, atrophic skinLoss of integumentary appendages,hair lossTypical acral necrosis

Examinations:Palpation of foot pulsesDoppler examination with occlusivepressure measurement(ankle-arm index, hydrostatic toepressure)Duplex ultrasonographyTranscutaneous oxygen measurementInvasive and non-invasive radiologicalprocedures (DSA, angiography, CO2 -angiography, MRI angiography)

42

Clinical picture of diabeticosteoartropathy with theassociated x-ray image: multi-ple fractures in the medialpart of the foot with completeloss of the original plantararch

In occlusive pressure measurements, an ankle-armindex of less than 0.9 is an indicator of arterial occlusivedisease, irrespective of the existence or otherwise ofmedial calcification119. Calcification of the tunica media ofthe arteries, described for the first time in 1909 byMönckeberg and named after him, is found in a high per-centage of diabetics120. As a result the vessels becomerigid and the occlusion pressures measured by Dopplerpressure measurement are false. The presence ofan occlusion of the vascular lumen or a reduction in thecirculatory reserve due to calcification cannot beexcluded121.

Evidence, however, has been found of a correlation bet-ween medial calcification and the primarily more distaltype of distribution of PAOD in diabetes patients122.Patients with existing medial calcification exhibit tibial orperoneal occlusive localisations of PAOD significantly

43

more frequently than diabetics without medial calcifica-tion or non-diabetics. Depending on the literature source,the arteries are assumed to be incompressible with anankle-brachial index (ABI) of 1.35 or 1.5123.

Indices of more than 1.2 may be considered indicators ofthe presence of medial calcification122. The most definiteevidence is provided by taking an X-ray of the forefootin which the medial calcification is visualised as a classic“tramline finding”120.

Media-calcification is a feature that is also increasinglyfound with advancing age, even in non-diabetics. Indiabetics, however, the presence of diabetic neuropathypredisposes to its early onset, particularly where auto-nomic nerve fibres are also involved (loss of modulationof vessel tone)120. The degree of calcification of thearteries correlates with the vibration perception and theduration of the diabetes124. In patients with pronounceddiabetic osteoarthropathy, in which the involvementof autonomic nerve fibres is typical, media-calcificationis found in 80–90% of cases120. As has already beenmentioned, hydrostatic toe pressure measure-ment116,117,118 may be used for diagnostic purposes, aswell as oscillography. In diabetics, there is often aphysiologically lower pressure in the area of the toearteries, relatively little calcification of the media and theunmasking of media calcification on elevation of theextremity above heart level. Values of more than70 mmHg may be regarded as normal findings in thiscase.

In summary, Mönckeberg’s arteriosclerosis is a non-occlusive angiopathy typical of diabetes mellitus andspecific to the presence of diabetic neuropathy. It ispossibly of prognostic significance for the subsequentappearance of a peripheral arterial occlusive disease(PAOD) and the occurrence of fatal myocardial infarc-tion125.

44

The significance of microcirculatory disorders at thecapillary level in the onset and course of diabeticfoot lesions is still a matter of debate. The presence oflumen-occluding, processes in the microcirculationof diabetics126,127 was used before as justificationfor early and extensive limb amputation. Today, the pre-sence of occlusive disease can be meassured andhence excluded. However, functional abnormalities of themicrocirculation with deterioration of haemodynamic,endothelial and cell function as a consequence of poorblood glucose control, must be considered definite128.These conditions impair healing. At present, capillarymicroscopy, laser flow measurement and transcutaneousoxygen measurement are standard procedures used inthe investigation of microcirculatory problems. There-fore the presence of gangrene with palpable foot pulsesin patients with diabetic foot syndrome should nolonger be considered a consequence of an occlusivemicroangiography, but much more as evidence of aneuropathic infected foot with the presence of septicemboli, and hence treated accordingly120,129.

Fontaine’s staging of PAOD is often of only limited use indiabetics when it is accompanied by diabetic neuropathyinvolving loss of pain perception. Measurement of theclassic ischaemic pain following exercise (Fontaine stageII) and the presence of resting pain (Fontaine stage III)have limited significance. Occasional neuropathic irrita-tion states are sometimes difficult to differentiate fromresting pain in arterial occlusive disease. The essentialaim should therefore be appropriate clinical examinationand directed investigation. Ultrasound imaging of thearteries and further angiographic investigations (conven-tional angiography, digital subtraction angiography,MRI angiography130 and CO2 angiography131) accordingto the guidelines of the European Consensus Paperof 1990 should be performed in primarily neuropathiclesions with delayed healing before any amputationis recommended in diabetic foot ulcers or gangrene.The imaging should always include the foot arteries115.MRI angiography may be expected to replace currentangiographic methods in the medium term due to itssuperiority in detecting occlusion distances and its highcost efficiency130. CO2 angiography also exhibitsmarked advantages over the procedures currently usedthrough its non-allergising method and the absenceof renal toxicity131.

45

Classification of diabetic foot lesions

The optimum treatment for diabetic foot syndrome in-volves the multidisciplinary team. It assumes clearcommunication between the various members of thetreatment team and requires a clear classification ofdiabetic foot lesions. The requirements made of classifi-cations are illustrated below, the most frequently usedclassifications presented and their clinical significancedescribed.

Co-operation and communication are mutuallydependent and assume clarity and accuracy in theclassifications used for planning therapy and forsubsequent comparability.

A clinical description is a specific snapshot of a parti-cular lesion and changes as the clinical situationimproves or deteriorates. An effective description shouldnot only provide someone else with an indicationof the best possible immediate therapy, but should alsoindicate the urgency with which such treatment shouldbe undertaken. A classification, however, should beapplicable at all times and to a variety of lesions. A goodclinical description of foot lesions should include detailsabout the patient (including social aspects), the affectedfoot (side, localisation, cause of lesions) and the lesionitself (size, severity, infection, stage of wound-healing)132.

One difficulty in establishing classifications of diabeticfoot lesions lies in the fact that they must be simpleenough to be understood by all team members(specialist or non-specialist)133. Also, they must be flexi-ble enough to cover all conceivable lesions and atthe same time specific enough to be able to define anindividual lesion clearly. A good classification alsomakes it easier to establish the prognosis for diabeticfoot lesions134.

Described in 1976 by Meggit133 and further refined byWagner in 1981, the so-called Wagner classificationhas become one of the most widely used classificationsof diabetic foot lesions world-wide. It comprises sixstages (0–5). Grade 0 corresponds to the pre-lesion(e.g. callous formation or condition following a healedfoot lesion). Grade 1 and grade 2 describe surface anddeep ulcerations. Grade 3 severity involves the presenceof deep ulcerations complicated by infection of boneand joints. Grades 4 and 5 describe localised and exten-sive necrotic developments. The classification has the

46

advantage of being very simple, but the disadvantageof being imprecise. Modifications by Harkless (supple-mented with the suffix B for ischaemic extremities) orReike (indication of the main aetiopathogenetic factors)have further refined these classification in terms oftheir use in practice133,136.

Wagner’s classification

Grade

0 No lesion, possibly foot deformity or cellulitis

1 Superficial ulceration

2 Deep ulcer as far as joint capsule, tendons orbones

3 Deep ulcer with abscess formation, osteomyelitis,infection of joint capsule

4 Limited necrosis in forefoot or heel region

5 Necrosis of whole foot

The University of Texas Wound Classification Systemhas been available as an alternative to this since 1996137.In this classification 4 degrees of severity are distinguis-hed (0, I, II, III). Severity grade 0 describes a pre- orpost-ulcerous state with complete epithelialisation. GradeI refers to a superficial wound, and Grade II to a woundthat has extended to the tendon or capsule. Grade IIIdescribes a wound with bone or joint involvement. Allgrades then have the suffix B appended in the presenceof an infection, suffix C for concurrent ischaemia andsuffix D for the concurrent presence of an infection andischaemia. For example grade III D would be a lesionwith ischaemia and infection in the presence of boneinvolvement. Grade II A would be a superficial woundwithout signs of infection or ischaemia.

47

The authors Lavery, Armstrong and Harkless evaluatedthe system in 1998 while studying more than 360patients138. A grade III lesion (bone or joint involvement)indicated an eleven-fold increase in the risk of ampu-tation. Patients with ischaemia and infection (stage D)exhibited a 90-fold higher risk of amputation.

Rischbieter and Reike in 1998 presented a similar eva-luation for the modified Wagner classification. Patientswith lesions of Wagner stages 4 and 5 (localised andgeneralised necrosis) had a nine-fold greater risk ofamputation than patients with lesions of Wagner stage0 to 3136.

48

University of Texas San Antonio – Diabetic Wound Classification(Armstrong’s classification)

Grade0 I II III

A

B

C

D

Completelyepithelialisedpre- or post-ulcerous lesion

Completelyepithelialisedpre- or post-ulcerous lesionwith infection

Completelyepithelialised pre-or post-ulcerouslesion withischaemia

Completelyepithelialisedpre- or post-ulcerous lesionwith infectionand ischaemia

Superficialwound withouttendon orcapsule involve-ment

Superficialwound withouttendon orcapsule involve-ment withinfection

Superficialwound withouttendon orcapsule involve-ment withischaemia

Superficialwound withouttendon orcapsule involve-ment withinfection andischaemia

Wound withtendon orcapsuleinvolvement

Wound withtendon orcapsuleinvolvement withinfection

Wound withtendon orcapsule involve-ment withischaemia

Wound withtendon orcapsule involve-ment withinfection andischaemia

Wound with boneor jointinvolvement

Wound with boneor joint involve-ment with infection

Wound with boneor joint involve-ment withischaemia

Wound with boneor joint involve-ment with infectionand ischaemia

49

Diagnosis structure in diabetic foot syndrome(modified by H. Reike)

1. Underlying disease(neuropathy, arterial occlusive disease, mixed form,osteoarthropathy)

2. Localisation(e.g. toes, forefoot, heel region, scar regions)

3. Extent of injury(e.g. Wagner’s stages 0–5;Armstrong’s classification)

4. Wound healing stage(cleaning, granulation andepithelialisation phase)

5. Infection(yes/no; limb threatening, non-limb threatening)

A precise description and classification of diabetic footlesions is essential for planning therapy, establishingthe prognosis and comparing diabetic foot changes andshould therefore be recorded meticulously.

50

Basic principles of thetreatment of diabetic footlesions

At present, treatment procedures for diabetic footsyndrome considered to be of proven efficacyinclude:1. Pressure relief of the affected parts of the foot2. Repeated and adequate mechanical

débridement3. Phase-specific moist wound treatment4. Medical and surgical treatment of infection5. The use of reconstructive and interventional

procedures to improve blood circulation(with due allowance for the specific features ofarterial occlusive disease)

Procedures such as the use of hyperbaric oxygen(HBO), the application of bio-engineered tissues andgrowth factors or biomechanical wound treatmentwith the use of fly larvae (where strictly indicated) maybe regarded as supplements to the basic therapybut not as a replacement for it.

Possibilities of pressure relief

As has already been mentioned, biomechanical changesare a frequent consequence of diabetic neuropathy,resulting in an altered pressure load on the sole of the

Partial foot relief shoe (forefootrelief shoe, Thanner company)to maintain the mobility ofpatients with plantar and acrallesions during the recoveryphase

51

foot. The combination of diabetic neuropathy and footdeformities increase the risk of ulcer formation.Therefore consistent pressure relief is an essential pre-condition for the prevention and healing of foot ulcers.

There is evidence of accelerated and persistent heal-ing with various treatment approaches, such as bed rest,wheelchairs, the use of a total contact cast (plastertreatment) and partial relief shoes139. The advantagesand disadvantages of the latter two procedures will bepresented below in greater detail.

Plaster treatment in the form of a total contact cast (TCC)currently represents the gold standard in the USAand Great Britain for pressure relief in plantar pressurelesions of the diabetic foot139,140,141. The benefit orrelatively short healing time, approximately five weekswith a pressure reduction of 75% to 85% contrasts withthe high cost (about 200 dollars), the need for regularchanges of the cast and the risk of infection with

Modified Allgöwer walkingapparatus for maximumpressure relief in patients withacute diabetic osteoarthro-pathy

52

increased difficulty of detection142. Probably the mostextensively used method of pressure relief in Germanyis the use of so-called partial foot relief shoes. Thesewalking aids are considerably cheaper than plastertherapy, but slightly less effective in terms of healing rateand degree of pressure relief140. In a case control study,96% of wounds in patients with forefoot relief shoeshealed within an average of 70 days, whereas in patientswithout such walking aids only 59% of ulcers healed(mean healing time of 118 days). Hospitalisation wasnecessary in half the patients without walking aids, butin only one out of 26 patients fitted with forefoot reliefshoes143. The principal difficulties encountered bypatients from the use of such accessories include:

1. The development of blisters or pressure points2. Pain in the joint area3. Difficulties in walking because of the difference in

height from the contralateral shoe4. Tearing of the walking sole142

Other options for pressure relief in specific cases(e.g. deformity in osteoarthropathy with ulcer formation)in our outpatient department include the use of Allgöwerwalking apparatus, aircast splints or custom-madetwo-layer orthoses.

Structured wound treatment and importance ofinteractive wound dressings

Wound healing in diabetic foot syndrome is a complexprocess, the purpose of which is to fill the tissue defectthat has occurred, restore sufficient strength to thetissue and re-create the physiological barrier betweenthe internal and external environment. In the courseof this, complex cellular biochemical processes result inthe formation of low-grade scar tissue. Wound healingusually occurs in three phases:

1. wound cleansing (inflammatory phase)2. the granulation phase (proliferative phase) and3. the epithelialisation phase

(differentiation phase, wound closure).

53

Differences are found between diabetics and meta-bolically healthy patients in all three phases and theseare described in greater detail below.

Immediately after an injury local blood coagulationoccurs with the formation of a fibrin network. Thisthen dissolves to allow the unimpeded extension of theensuing granulation tissue. In diabetics, these fibrincoatings occasionally persist beyond the first phase144.

Schematic representation ofthe time course of the woundhealing phases:1) inflammatory phase2) proliferative phase3) differentation phase

Extensive necrosis of the healwith local erythema

Wound in the inflammatoryphase with wound coatingas well as maceration andnecrosis formation at themargins

54

Subsequently a local inflammatory reaction develops,in which first neutrophils (which release proteases andare capable of phagocytosis) and then macrophagesmigrate to the wound area where they release messen-ger substances, known as cytokines (such as PDGFor TGF-(β). These mediators stimulate cell activities suchas angiogenesis, autolytic débridement, keratinocytemigration, matrix formation and fibroblast formation.

There are deficiencies in diabetics in respect of both thebactericidal activity of the neutrophils145 and the pro-perties of the fibroblasts146,147.High glucose and lactate levels cause disruption of therate of fibroblast division and resistance to growthfactors. In addition to these acquired changes of immunefunction, there is also assumed to be a geneticallypredetermined disorder of immunocompetence in dia-betics148. As a result of the proliferation of vascular

Ulceration of the heal in thegranulation phase

Increasing wound closure inthe epithelialisation phase

55

endothelial cells and fibroblast formation, a shiny redgranulation bed is formed and collagen synthesis isincreased.

Finally, wound closure occurs through epithelialisation.The formation of an epidermis serves as protection,though it does not improve the strength of the new tissueany further.

There are two types of wound healing.

1. Primary wound healing occurs through primary adap-tation with only small quantities of granulation tissue.

2. Secondary wound healing takes place in infected andnecrotic tissue, whereby wound closure occurs mainlyby contraction. In the second form, adaptation canbe assisted by the use of Omnistrip® wound suturestrips for example.

Pressure site on the lateralborder of the foot with septicischaemic necrosis of thefifth toe. Bilateral resection ofthe fourth and fifth ray follow-ing insertion of a plastic cruralbypass

Healing of the resectionwound with phase-specificwound treatment

56

Disruptive factors in wound healing may be systemicor related to local conditions in the wound area. They arelisted here:

Possible causes of impaired wound healing indiabetic foot syndrome

Systemic factors:Hyperglycaemic metabolic situationMalnutritionObesityNicotine abuseAnaemiaRenal insufficiency/uraemiaPatient’s ageDrugs (steroids, antirheumatic agents).

Local factors:Ischaemia and hypoxia of affected tissuePressure loadRepeated traumaInadequate local wound treatmentInfectionNecrosisOedema formationForeign body in the wound

Successful local wound treatment must fulfil the followingconditions:

It must:

1. Support normal biological healing processes,2. Prevent infection and/or reduce the microbial count,3. Prevent necrosis formation and/or eliminate existing

necrosis,4. Be based on a phased wound healing process,5. Be cost-effective6. Be well tolerated by the patient and applicable for

outpatients.

In the therapy of chronic wounds, moist wound treat-ment using modern differentiated wound therapy hasnow replaced the previous conventional wound treatment– consisting of various dyes, local administration of anti-microbial substances and sterile dressings.

57

In the first phase of wound healing, the mechanicalor physical removal of necrotic tissue, the provision ofdrainage for exudate and where necessary the resectionof infected bone sequestra take precedence. In addition,deoxyribonucleases (e.g. Fibrolan®), streptokinase-streptodornase (e.g. Varidase®) or collagenases (e.g.Iruxol® N) may be used. There are at present no studiesthat confirm the efficacy of these preparations.

Septic thrombosis withgangrene of the second toe ofthe right foot with extensivedeep foot infection in the ab-sence of an arterial occlusivedisease

Subsequent healing processfollowing amputation ofthe second to fourth rays andinfected sections of tissuewith phase-specific woundtreatment

58

In terms of special wound dressings, alginates(e.g. Sorbalgon®) are used at this stage for wounds withprofuse exudation and are also suitable for deepand gaping wounds. Wound healing complications havebeen described in individual cases with alginatetherapy in undiagnosed deep wound infections, osteitisor minimally exudative wounds149,150.

In non-infected wounds of Wagner stages 1 and 2 withonly mild to moderate exudation, the use of hydrogels(e.g. Hydrosorb®) or hydrocolloids (e.g. Hydrocoll®) maybe considered for moist wound treatment. The hydro-gels are polyurethane meshes with a 60% or higher watercontent, depending on the product. In contrast to thehydrocolloids, they do not form a gel and thereforeabsorption of exudates is possible. As a result of the highwater content, the main effect of hydrogels in diabeticfoot syndrome lies in the softening of necrotic tissue andwound coatings.

By reducing the frequency of dressing changes, treat-ment with special wound dressings becomes cost-effective. Despite the difficulties of comparability bet-ween studies (due to use of different preparationsin different stages of healing), the application of hydro-colloids resulted in reduction in costs by 60% in com-parison to dry or moist gauze dressings151. In addition tothe dressings described, Ringer’s solution administeredeither as a continuous irrigation or in carrier media suchas superabsorbent polyacrylate (e.g. TenderWet®) issuitable for moist wound treatment in the late cleansingand granulation phase. Because of its mechanicalprotective action, the continuous release of the absorbedRinger’s solution and its high absorption capacity forwound exudate, this product is particularly suitable forthe outpatient treatment of diabetic foot lesions.Lastly, epithelialising wounds are covered with a non-medicated, ointment-impregnated gauze.

As the skin of neuropathic patients is very fragile, wounddressings and bandages in our hospital are securedexclusively with gauze bandages and gauze dressings.In ambulant patients, tubular dressings are also appliedto prevent the primary bandage from slipping. Directcontact of the fixation plaster with the patient’s skinis avoided where possible because of the tendency to

59

macerate. The lack of adequate studies on the phase-specific use of sufficient wound dressings results on theone hand in inappropriate use by unspecialised users152,and on the other in a constant debate among expertsabout the risks of using specific wound dressings indiabetics149,153,154. In a large English survey on the use ofspecific wound dressings in diabetic foot syndrome,five to eight different wound dressings were mentionedby each user, among which hydrocolloids, hydrogelsand alginates were the most widely used. None of theproducts, however, had more than 30% support in anyof the wound healing phases. This survey was unable toclarify whether this finding is due to a lack of information,or to the belief on the part of the users that there areno essential differences between the various dressings152.Encouraged by individual case reports, the use of hydro-colloid dressings in diabetic foot syndrome has becomea subject of debate in recent years.

Problems identified in the use of hydrocolloid dressingsinclude:1. Rapidly progressive infections under occlusive

dressings2. Gel particles incorporated in wounds as foreign bodies3. Maceration and pressure injuries of wounds have been

described.

Pre-existing infection of the wound and weekly changesof dressings were common to all the case reports withfatal outcomes. By complying with the contra-indi-cations and observing shorter intervals between changesof dressings, such complications could definitely beavoided. In contrast to these case reports, an infectionrate of only 2.6% under occlusive dressings has beenobserved in large-scale studies, which compared to 7.1%with conventional dressings155.

Stage-specific application of the treatment principles,regular débridement and strict monitoring of the woundstatus in the initial phase (at least twice daily changes ofdressings in infected wounds) are essential preconditionsfor successful treatment. An important component oftreatment also involves actively including the patient andtheir relatives at this early stage and preparing the wayfor the transfer of individual responsibility.

60

Moist wound treatment

In wounds healing by secondary intention, moist woundtreatment is now considered the standard and hasbecome accepted in particular in the treatment ofchronic problem wounds. The scientific bases for moisttherapy were established in the studies by Winter (1971).He showed that a moist and permeable dressing madethe wound heal quicker than a dry wound exposed to air.This fact is also confirmed by more recent studies.According to Turner (1990), permanent moist woundtherapy results in a significantly faster reduction in woundarea and a larger quantity of granulation tissue than incontrols. Accelerated re-epithelialisation is alsoobserved. In addition, moist wound dressings exhibit agood wound healing effect without damagingimmunocompetent cells.

Wound dressings for moist treatment

A series of wound dressings are now available for thepractical implementation of moist wound therapy,covering the whole spectrum of therapeutic requirementsin terms of a treatment system.

TenderWet – Wound dressing pad with superabsorbentcore

TenderWet is an extremely efficient wound dressing forthe treatment of chronic infected and non-infectedwounds during the cleaning phase and at the beginningof the granulation phase. The basis of its high degree ofefficacy is a special principle of action that allowscontinuous “rinsing” of the wound.

TenderWet is a multilayer wound dressing pad containinga superabsorbent polyacrylate core as its centralcomponent which has irrigating properties. Thesuperabsorbent core is activated before use with asuitable volume of Ringer’s solution, which is thendelivered continuously to the wound over a period oftwelve hours. This constant supply of Ringer’s solutionactively softens and detaches necrotic tissue (1).

At the same time, the absorbent core reliably takes upand retains germ-laden wound exudate. This exchangeis possible because the superabsorbent core has agreater affinity for protein-containing wound exudate thanfor salt-containing solutions (Ringer’s solution). Thewound exudate therefore displaces the Ringer’s solution

The principle of action ofTenderWet

1

2

3

61

from the wound pad (2).Thus, TenderWet continuouslyrenews the film of Ringer’s solution over several hoursand simultaneously absorbs micro-organisms, releaseddetritus and toxins. Hence, the wound is “rinsed” andrapidly cleansed.

As soon as the factors that inhibit wound healing areeliminated and the wound area is clean, granulationtissue can build up through the migration of cells and theregeneration of vessels (3). In the course of this, themoisture and the electrolytes in the Ringer’s solution,such as sodium, potassium and calcium, contribute tocell proliferation.

TenderWet has no contra-indications and can also beused in infected wounds. In individual cases, anapparent enlargement of the wound occurs followinginitial cleansing with TenderWet. This means thatundetected devitalised tissue has also been eliminatedby this method.

The amount of Ringer’s solution necessary to activate theabsorbent/ rinsing core depends on the size of thedressing. In deep wound conditions, TenderWet shouldbe packed loosely to ensure the direct contact that isrequired for fluid exchange to occur. The physicalproperties of the superabsorbent compound, combinedwith the covering of knitted fabric, give TenderWet thenecessary packing properties. In extensive wounds, theTenderWet wound pads should be applied so that theyoverlap slightly. They can then be covered as necessarywith a gauze fixation dressing.

TenderWet is available invarious shapes and sizes toensure good adaption to thevarious wound conditions.TenderWet is activated withRinger‘s solution directly in thesterile peel – off package(right)

62

TenderWet dressings as a rule should be changed twicedaily, i.e. every 12 hours. TenderWet 24 can be used at24 hour intervals. TenderWet 24 is made of the samematerials as TenderWet, but is designed so that theRinger’s solution absorbed is released more evenly andthe absorption/rinsing action persists over 24 hours. Inaddition, a moisture-repellent layer is incorporated insidethe dressing to prevent moisture penetrating and thusprovides a dressing that offers excellent moist therapy.

Sorbalgon – conformable calcium alginate dressings

Sorbalgon is the ideal wound dressing for cleansing andfor expediting the build-up of granulation tissue infissured wounds and those that are difficult to manage.Sorbalgon is highly adaptable and thus ensures effectivewound cleansing and management, even in deepwounds.

Sorbalgon is a non-woven dressing of high-gradecalcium alginate fibres which is applied to the wound inits dry state (3). On contact with sodium salts, such asare found in the blood and wound exudate, the fibresswell and are transformed to a moist, absorbent gel thatfills the wound (4). Sorbalgon approximates closely tothe wound surfaces, therefore micro-organisms even ata deep level are absorbed and incorporated safely inthe gel structure (5). This results in efficient microbialreduction and helps prevent recontamination. Woundsare rapidly cleansed, so that Sorbalgon has becomeestablished in the treatment of chronic and infectedwounds in particular.

The gelatinous consistency of Sorbalgon also acts like amoist dressing, preventing dehydration of the wound.A favourable microclimate for wound healing arises, pro-moting the formation of granulation tissue and keepingthe wound surfaces supple.

TenderWet has nocontraindications and can beused in all wound conditions,both infected and non-infected. The “rinsing effect” ofTenderWet is optimal duringthe cleaning phase and at thebeginning of the granulationphase. The examples showTenderWet used in the care ofa venous (1) and an angio-pathic/diabetic ulcer (2)

The principle of action ofSorbalgon

3

4

5

1 2

63

As Sorbalgon is able to be transformed into a gel, itdoes not adhere to the wound and changes of dressingcan be made painlessly. The complete transformationof the calcium alginate fibres to a gel requires sufficientexudate. Thus, where fissured wounds with little exudaterequire packing, Sorbalgon should be moistened withRinger’s solution. Any fibres remaining in the wound canbe rinsed out with Ringer’s solution, otherwise the gelplug is removed from the wound with forceps.

The frequency with which dressings are changed de-pends on the individual wound conditions. In the woundcleansing phase, one or two changes of dressing arenecessary, depending on the degree of exudation. Later,with granulation formation, a change of dressing every2 to 3 days may be sufficient. Sorbalgon is supplied insquare dressings of two sizes. Sorbalgon T ribbons areavailable specifically for larger wounds.

Hydrosorb – hydrocellular gel dressing

Hydrosorb is especially suitable for moistening andprotecting granulation tissue and young epithelium andis hence the optimum wound dressing for phase-specifictreatment following TenderWet or Sorbalgon therapy.

Hydrosorb is a ready-to-use gel made of absorbentpolyurethane polymers which has a high water content(60%). Thus, from the very beginning Hydrosorb auto-matically provides a moist environment for the wound forseveral days (1). At the same time, Hydrosorb absorbsexcess exudate, which is then incorporated in the gelstructure. This exchange guarantees the optimal levelof moisture for wound healing and thus accelerates gra-nulation formation and epithelialisation (2). The germ-proof and waterproof surface of Hydrosorb alsoguarantees protection against secondary infections.

Loosley packed Sorbalgondressings (left) and theirtransformation to a gelatinousstructure by the absorptionof exudate (right)

The principle of action ofHydrosorb

1

2

64

Hydrosorb does not stick to the wound and can beremoved even after prolonged application without therisk of irritation to the wound. Unlike hydrocolloids,Hydrosorb can be removed in one piece since the gelstructure is not dissolved by the absorbed woundexudate. No residues are left on the wound and thewound condition can be assessed safely without priorrinsing.

One particularly practical advantage of Hydrosorb isits transparency, which lasts even after prolonged appli-cation. As a result the wound can be inspected withoutremoving the dressing. This ensures rest for the woundwhich is so important for healing, as well as a highdegree of cost effectiveness because of the reducedfrequency of dressing changes.

Hydrosorb is available in two forms: Hydrosorband Hydrosorb comfort. Both hydrogels have the sameprinciple of action, but differ in terms of methods offixation. Hydrosorb does not have a self-adhesive borderand as a rule is secured by means of a fixationdressing, adhesive plasters or a dressing retentionbandage.

Hydrosorb comfort has a hypoallergenic adhesive filmborder to ensure it stays firmly in place and to preventbacterial penetration. This, together with the germproofand waterproof surface of Hydrosorb comfort, simplifiesdaily hygiene.

Hydrocoll – absorbent hydrocolloid dressing

Hydrocoll is a self-adhesive, absorbent hydrocolloiddressing for the cleaning and management of non-infect-ed wounds.

The term “colloid” comes from the Greek and means“a substance that is incorporated in a matrix in a veryfine distribution”. Hydrocoll consists of absorbent and

The transparency of Hydrosorbis an important factor in itscost-effective use. The woundcan be inspected at manytimes through the dressing sothat Hydrosorb can remainin place on the wound for daysand the number of changesof dressings is reduced

65

expandable hydrocolloids incorporated in a self-adhe-sive elastomer with a semipermeable film that serves toprevent the penetration of bacteria and moisture. Uponabsorption of exudate from the wound, the hydrocolloidalparticles swell to form a gel that expands into the woundand maintains a moist wound environment (1). The gelremains absorbent until the hydrocolloids are saturated.Saturation of the hydrocolloids is indicated by a blister-shaped protrusion of the dressing (2), whereupon theHydrocoll must be changed.

Due to the adhesiveness of the elastomer, Hydrocoll canbe laid on the wound like a plaster. With the formationof the gel, however, the adhesiveness in the area of thewound surface is lost, so that Hydrocoll is attached onlyto the intact border and thus does not affect the wound.In addition, when the dressing is removed, it can beremoved without leaving residues of gel on the wound.Prior irrigation is not necessary for assessing the woundafter a change of dressing. Hydrocoll has a high ab-sorbency due to the special material composition.Excess contaminated exudate is rapidly absorbed andsafely retained in the gel structure as a result of theswelling process. In this way the microcirculation inthe wound area is simultaneously improved, so that thebody’s own cleansing mechanism is reactivated,especially in those chronic wound conditions wherehealing is delayed.

During the granulation phase, the moist wound environ-ment under Hydrocoll particularly stimulates the activityof fibroblasts, which are responsible for initiating theprocess of tissue regeneration. During the epithelialisa-tion phase, the division and migration of epithelial cells issupported. If there are no complications, Hydrocoll canremain on the wound during this phase for several daysuntil the epithelialisation process is completed.

The germproof and waterproof top layer serves as areliable barrier against bacteria and protects thewound from contamination and penetration of moisture.Ambulant patients can shower with the dressing inplace.

The principle of action ofHydrocoll

1

2

66

Mo

ist

wo

un

d t

reat

men

tD

ry w

ou

nd

tre

atm

ent

Product characteristics

ZetuvitWound-compatible absorbent dressing pads withnon-adherent material covering and an absorbentcore of cellulose fluff

Cosmopor sterilSelf-adhesive wound dressing with waterrepellentmicrogrid wound contact layer, absorbent padof pure cotton wool and soft non-woven fabriccoated with a hypoallergenic polyacrylateadhesive

ComprigelImpregnated, non-adhering gel dressing withintegrated absorbent core in medicated cotton

AtraumanWound-compatible water-repellent polyestertulle, impregnated with a selfemulsifying, neutralointment, non-adherent

TenderWetSuperabsorbent polyacrylate wound pad withan absorbing/rinsing core, activated beforeuse with Ringer’s solution which is delivered tothe wound in exchange for wound exudate

SorbalgonConformable, non-medicated dressings made ofcalcium alginate which form a moist gel incontact with wound exudate

HydrosorbAbsorbent hydrogel dressing with high watercontent in the gel structure, covered with semi-permeable transparent germproof and water-proof layer

HydrocollSelf-adhesive, absorbent hydrocolloid dressingwith semi-permeable, germproof and waterprooflayer.

PermaFoamHydroactive foam dressing with a high levelof water vapour permeability top layer; but liquid-and germ-proof

67

Properties and use Commercial forms

highly absorbent, soft and drapable, permeable to air, goodcushioning effect; for the treatment of highly exudative, acute,superficial wounds, good protection against contamination throughintegrated, moisture-repellent cellulose layer preventing thepenetration of exudate

rapid transfer of exudate into the absorbent pad as a result ofthe water-repellent microgrid, no adhesion, good absorbency andcushioning effect, permeable to air and water vapour, adhesiveborder ensuring good closure; for postoperative wound managementand the sterile dressing of minor injuries, e.g. in first aid.

highly absorbent, permeable to secretions and air, does not adhere tothe wound and keeps wound edges supple; slightly cooling, pain-relieving effect; for the treatment of acute, small, superficial woundsor minor injuries

permeable to air and secretions, no adhesion to the wound, noresidue on the wound as a result of self-emulsifying ointment, doesnot have a sensitising effect; to maintain suppleness in acute andchronic wounds, particularly in dermatology and in patients with sen-sitive skin or who are sensitive to medications

rapid wound cleansing and promotion of tissue cell proliferationthrough the continuous supply of Ringer’s solution and thesimultaneous absorption of contaminated exudate (= rinsing effect);for the treatment of chronic, acute and infected wounds duringthe cleansing phase and at the beginning of the granulation phase

high absorbency with efficient cleansing effect, safe retentionof bacteria in the gel structure, maintains a moist environment forthe wound after formation of a gel, promotes granulation, no ad-hesion, highly conformable; particularly suited for the cleansing andmanagement of deep and gaping or infected wounds

from the very beginning provides a moist environment for the wound,transparency allows inspection of the wound at any time withoutthe need to remove the dressing (= high cost effectiveness throughreduction in frequency of dressing changes); ideal for moisteninggranulation tissue and epithelium following TenderWet or Sorbalgontherapy

as a result of the promotes granulation, no adhesion to the wound;particularly suitable for the management of chronic, slow-healingwounds and where the granulation process is not functioningsatisfactorily

Zetuvit,sterile and non sterile10x10, 10x 20, 15x 2520 x 20 and 20x 40 cm

Cosmopor sterile,7.2x 5, 10x6, 15x6, 10x8,15x8, 20x 8, 20x 20, 25x10and 35 x10 cm

Comprigel, sterile,5 x 7.5, 10 x10 and 10 x 20 cm

Atrauman, sterile,5 x 5, 7.5x10 and 10 x 20 cm

TenderWet, sterile,∅ 4, ∅5.5, 7.5 x7.5 and10x10 cmTenderWet 24, sterile∅ 4, ∅5.5, 7.5 x7.5 and10x10 cm

Sorbalgon, sterile,5 x 5, 10 x10 and 10 x 20 cmSorbalgon T tamponade ribbon,sterile, 1g/30 cmand 2g/30 cm

Hydrosorb, sterile, 5 x7.5, 10 x10and 20 x 20 cmHydrosorb comfort, sterile,4.5 x 6.5, 7.5 x10, 12.5 x12.5,11.5x24 and 21.5 x 24 cm

Hydrocoll, sterile, 5x5, 7.5x7.5,10 x10, 15 x15 and 20 x 20 cm;Hydrocoll sacral, 12x18 cm;Hydrocoll concave, 8x12cm;Hydrocoll thin, 7.5x7.5, 10 x10and 15 x15 cm (all sterile)

the special pore structure of the hydrophilic foam dressing enablesrapid absorption of the wound exudate and creates a moistwound environment that stimulates wound healing; change of thedressing is atraumatic

PermaFoam, sterile,10 x 10, 15 x 15, 10 x 20 and20 x 20 cmPermaFoam comfort, sterile,11 x 11, 15 x 15, 10 x 20and 20 x 20 cm

68

Treatment of infection

Inflammation is a physiological reaction of the bodydesigned to protect the tissues and to aid the eliminationof harmful agents. These harmful factors may be micro-organisms or chemical substances (acids or bases),but they can also be friction, pressure, foreign bodies, orof a physical nature (e.g. an effect of temperature).Infection in this context means the transmission, ad-herence and penetration of micro-organisms to and intoa macro-organism. This can result in the developmentof an infection, depending on the infectious and patho-genic properties of the micro-organism, but also on thedefensive and offensive forces of the macro-organism(immunity). Infection is not a primary cause, but the mostsevere complication in diabetic foot syndrome and isassociated with impaired wound healing and an increas-ing risk of amputation. The best prophylaxis againstwound infections is the destruction of the favourableliving conditions for pathogenic micro-organisms throughdrainage of the exudate and elimination of necrosis,but also through specific drug therapy and early (minor)surgery, where necessary.

Superficial and deeper, uncomplicated neuropathicforefoot ulcers (Wagner stages 1 and 2) heal as rapidlywith standardised, phase-specific therapy without theadministration of antibiotics as they would with antibiotictherapy. The mean reduction in ulcer size in this caseis 0.25 mm/day156. In patients in whom specific diseaseconditions point to the possibility of a modification of thenatural healing process (patients with severe ischaemia,with renal insufficiency or immunosuppressant diseases),antibiotic treatment should be considered at an earlystage, even with this degree of severity156,157. At the sametime, the importance of long-term antibiotic therapyof foot ulcer patients in the development of multiresistantorganisms should not be underestimated (e.g. a methi-cillin-resistant Staphylococcus aureus – MRSA).This micro-organism now constitutes up to 25% of allstaphylococcal infections in diabetic foot syndrome158,159.In foot infections in which preservation of the extremityis not threatened and which can be treated on an out-patient basis, aerobic Gram-positive cocci (e.g. Staphy-lococcus aureus) are found in almost 90% of cases,

69

and constitute the sole pathogenic agent in about40%. Gram-negative aerobes (e.g. Klebsiella or Pseudo-monas) and anaerobic micro-organisms are found in36% and 13% of cases respectively, always in conjunc-tion with polymicrobial infections. In the study quoted,clindamycin and cephalosporins were used for antibiotictherapy, which in our outpatient department are replacedwhere necessary by Fluoroquinolones following theresults of cultures and in the absence of improvement inlocal findings160. Ninety percent of infections arehealed with these agents, 75% of them within two weeks.

The aim here is to prevent the development of deep in-fections or osteomyelitis (or more accurately osteitis,since initially it is the bone cortex that is affected and themost commonly affected small bones of the foot containhardly any marrow). Osteitis is mainly a polymicrobialinfection (about 80% of cases), between 50% and 80%of which involve staphylococci.

Drug therapy in deeper soft tissue infections and osteitisshould be based on sensitivity tests of the micro-organisms isolated from the tissues concerned (obtainedby wound swab, aspirate, curettage or surgical excision).Again clindamycin may be considered here161.With purely conservative therapy, long-term treatmentsof eight to twelve weeks are necessary162,163. The safestway of obtaining long-term eradication of bone infectionwithout threatening the integrity of the foot appearsto be early surgical removal of affected sections of bone.Early surgical intervention should be considered,particularly if the infection fails to respond to targetedantibiotic therapy, not least because an unhealedinfection involves the risk of an arthropathy occurringlater in the course of the disease164.

70

Redness and marked swellingof the second toe (sausagetoe) as a reliable sign of anunderlying osteomyelitis

There are a variety of expensive imaging procedures forthe diagnosis of osteitis in diabetic foot syndrome,such as leucocyte scans, Tc99m bone scan, magneticresonance imaging (MRI) and standard X-rays.A simple and cheap method with at least as high a

positive predictive value for the presence of osteitis (89%versus 75%–85% with leucocyte scans and 50%–93%with MRI) is the “tube test”. Access to the bone viathe existing lesion with a sterile rinsing tube indicatesthe presence of osteitis with a high degree of accuracy165.Clinical signs (reduced pain perception due to neuro-pathy) and biochemical indications of osteitis are muchless reliable in diabetics. Fiftyfour percent of all patientswith osteitis in an American study were within the normalrange in terms of the leucocyte count, while in 82% ofthe affected patients the oral temperature measured wasnormal166.

Targeted action, however, presupposes an adequatediagnosis. In a follow-up study of patients with infecteddiabetic foot lesions in an American teaching hospital,documented examinations of the wound for the involve-

71

ment of deeper structures were found in only 10% ofcases and a lack of foot X-rays was observed in 33% ofpatients. Blood cultures were arranged in 62% ofcases but tissue cultures from the wound in only 51% ofcases167.

Vascular and surgical interventions in thediabetic foot syndrome

Primarily neuropathic lesions usually have a tendency toheal rapidly following complete pressure relief, débride-ment, drainage of soft tissue infections and, wherenecessary, antibiotic therapy. In other cases where addi-tional ischaemia is found, immediate Infection controland consideration of Reconstructive or interventionalsurgery to improve perfusion should be attempted.Then, if unavoidable, borderline zone resection or Ampu-tation, sparing as much tissue as possible, is performed(IRA principle according to Vollmer168). It is essential thata complete clinical and instrumental examination is per-formed before every amputation in diabetics to identifythose patients who will benefit from vascular surgery169.This is made more difficult as concurrent diabetic neuro-pathy reduces the detection of ischaemic pain andtraditional methods of investigating blood circulation areof limited predictive value in the presence of mediacalcification.

There is as yet no documented evidence in large,controlled studies of an improvement in the prognosis forpatients with diabetic foot syndrome from drug therapywith prostaglandin derivatives. These products havenot been shown to have any specific effects in diabetics.A large Italian study showed a short-term improvementin the critical blood circulation of a limb and a reductionin the risk of amputation with prostadil (Prostavasin®).After six months’ observation, however, only moderatedifferences were found between treated and untreatedpatients170.

In a small study involving eight patients with a disorderof the arteries of the lower leg and rapid progressionof the foot lesion, urokinase therapy showed good short-term success. However, in the long-term a bypassoperation had to be undertaken in half the patients topreserve the extremity171.

72

It is thus apparent that patients with lesions of ischaemicorigin should be examined as rapidly as possiblewith a view to establishing their suitability for a surgicalprocedure (e.g. angioplasty, graft).

Some differences from non-diabetics are apparent withboth treatment approaches as a result of the particularanatomical circumstances. In principle, the results ofvascular surgery in diabetics are comparable to those innon-diabetics. In particular, a leg preservation rate of77% was found after 11/2 years with the dilatation of cir-cumscribed occlusions or stenoses of lower leg vessels172.In patients in whom a balloon dilatation remains technic-ally unsuccessful or in whom the leg condition failsto improve despite an initially successful operation, by-pass surgery procedures should always be considered173.Overall, the pool of patients who can be helped byvascular surgery is increased by the isolated dilatation oflower leg vessels. Advanced age, a long history ofdiabetes and a high degree of severity of the circulatorydisorders have an adverse effect on the results of thismethod in diabetics. Regular examinations to identifyasymptomatic vascular processes and the implementa-tion of surgical measures prior to the occurrence ofserious complications should therefore become standardprocedures174. Interventional (e.g. dilatation) and re-constructive (e.g. bypass surgery) procedures should beemployed as supplementary measures to preserve theextremity in diabetic foot syndrome. In 22% of patientsfrom the Augsburg Clinic in whom a cruromalleolarbypass was performed between 1986 and 1992, theblood supply had previously been optimised by a per-cutaneous transluminal angioplasty (PTA) of the femoralartery.175

Because of the particular anatomy (the lower legis frequently affected by PAOD, while the ankle and footarteries are spared), crural (bypass to a lower legvessel) or pedal (bypass to foot arteries) bypass proce-dures have increasingly obviated the need for ampu-tation in diabetics over the past few years. Previously, thecreation of a femoropopliteal bypass in combinationwith a transmetatarsal borderline zone amputation wasthe therapeutic procedure of choice in ischaemic dia-betic foot syndrome. There has been a marked reductionin the number of amputations required in diabetics post

73

Creation of a distal vein by-pass to preserve the extremity

the introduction of bypass procedures. In both the USA176

and Denmark177 the number of amputations in diabeticsmore than halved between 1984 and 1989, while by-pass surgery, angioplasty and above all the use of distalbypass grafts in each case more than doubled. In ad-dition, in those amputations that have still proved necess-ary, the level of amputation has increasingly moveddistally. The amputation rates in Germany in centresusing such procedures175,178 are less than 10% for majoramputation. The extremity is preserved in 75% and71% of cases after 2 and 5 years, respectively. Thepatency rates of the bypasses created are about 60%.This means that even short-term bypasses are frequentlysufficient to save a jeopardised extremity. As the dia-meters of the vessels in the lower leg and foot are small,

autologous materials, i.e. the patient’s own veins, shouldpredominantly be considered for bypass material. Inindividual cases, however, synthetic crural bypasses withsurvival periods of several years have been observedin our hospital. Peri-operative mortality of 1 to 2% in suchprocedures must be regarded as favourable175,178, whencompared to primary amputation as an “alternativemethod” which has a peri-operative mortality rate of 8%in minor amputations and 18% in major amputations175.

A precondition for the use of such procedures is goodangiography, with visualisation of the foot arteries76.Foot arteries that are suitable for bypass-surgery can befound in a large proportion of diabetics. Even in theabsence of any angiographic evidence, a suitable vesselfor a bypass can be found in half the remaining patientsby Doppler examination179.

74

Slight residual necrosis in thelarge toe…

…and non-irritant, secondarilyhealing wound followingresection of the necrotic fifthtoe

Surgical measures in the treatment of the diabetic footsyndrome are not simply based on amputation.If vascular surgical principles are applied, then extensivemutilation can be prevented. If an amputation cannotbe avoided because of insufficient perfusion or un-controllable infection, the principle that is now applied,is to preserve as much tissue and function as possible.

The classical amputation lines of previous years are nolonger binding and borderline zone amputations thatare as non-mutilating as possible are the procedure ofchoice, subject to local perfusion conditions.

In the toe region, especially the large toe, partialamputations are also beneficial for postural reasons.Transmetatarsal amputations in the forefoot area, asopposed to surgery of the mid-foot and hind- foot, havethe advantage of yielding better muscle balance with-

75

Forefoot stump which can bewell catered for by ortho-paedic measures (left) comp-ared with a functionallyunfavourable result followingamputation of the first, secondand fourth toe with a con-siderable risk of occurence offurther foot lesions (right)

out the risk of talipes developing. Total resection of toesinvolves a significant risk of the development of deficitsof mobility or rigid deformities180 which then requireparticular management. Amputations of the toes (parti-cularly of the first toe) also increase the risk of follow-upinterventions on the same side, as well as on the contra-lateral side as a result of altered weight-bearing181.

While the long-term outcome of surgical interventionson non-weight-bearing osteolytic sections of bone (e.g.resection of proximal interphalangeal joints) is non-problematic, pressure ulcers in the neighbouring areasor the induction of diabetic neuropathic osteoarthropathyare occasionally observed in surgery on weight-bear-ing sections of bone (e.g. metatarsal resection)182. Withthe long-term presence of ulceration (on average ninemonths), Griffiths183 was able to heal all patients byresection of the metatarsals within an average period ofthree months. No relapses were seen in any patient dur-ing a fourteen-month long follow-up observation phase.

A 70% reduction in pressure following resection of meta-tarsal I and 40–50% following resections of metatarsalsII to V was measured184. In our own patient population,plantar recurrences have been seen on isolated occa-sions in patients in whom individual metatarsals wereresected, but not in patients in whom metatarsals II to Vwere completely removed.

Successful revascularisation is the determining predic-tive factor in the healing of partial foot amputations185.Without prior revascularisation, 70% of partial foot

76

amputees must be re-operated, whereas after a suc-cessful revascularisation this applies in less than 20% ofcases. In contrast to patients with major amputations,patients with amputations at the foot and ankle level havea markedly higher probability of survival of almost 90%after four years and more than 75% after eight years186.However, re-ulceration occurs or further surgery is re-quired in more than 50% of patients. The whole group ofsuch patients is characterised by high morbidity witha further period of ulceration in almost 20% of casesfollowing a successful amputation. With appropriatecare, however, further surgery can be avoided in 52% ofpatients over an eight-year period. More than 2/3 ofpatients can be rehabilitated following a transmetatarsalborderline zone amputation and are able to walk withoutimpairment185. In contrast to forefoot amputees, patientswith amputation of the posterior foot area (by the Chop-art, Pirogoff and Syme methods) are not capable ofwalking without a prosthetic device, but these operationsallow the lower leg to be preserved187. The prognosisfor a Syme amputation depends in particular on goodlocal perfusion. With good circulation, 90% of Symeamputations heal and can be fitted with a prosthesis.After 21/2 years, two-thirds of patients still wear their pros-thesis throughout the day188. Among patients with a lowerleg amputation, 66% are able to walk with a prosthesis.Upper leg amputated patients are capable of walkingwith a prosthesis in 46% of cases, whereas bilaterallyamputated patients can be mobilised with a prostheticdevice in only 19% of cases189.

The mean survival time following major amputations isslightly more than three years and 50% of patientsare threatened with the loss of the other extremity withinfive years. Good aftercare of limb-amputated diabeticsis essential190. This involves care of the contralateral limband also good social reintegration.

In the case of extensive skin defects, the possibility ofplastic surgery to cover the defect should be consideredat an early stage191. Split-skin grafts, mesh grafts orisland flaps are available for wound closure.

Importance of adjunctive treatment methods

Hyperbaric oxygen therapy (HBO)

Hyperbaric oxygen therapy has been debated for someyears as a possible supplementary method for thetreatment of poorly healing wounds. On the assumption

77

that the combination of hypoxia and infection is respon-sible for the delayed healing of diabetic foot lesions,the oxygen tension of the affected tissue should beincreased through the application of hyperbaric oxygenin high-pressure chambers. It is thought that oxygentension remains high for a prolonged period after expo-sure. Thus the development of necrosis in the affectedtissue is reduced. In addition, a direct inhibitory effecton the growth and toxin production of anaerobic micro-organisms and a potentiating effect on angiogenesisare postulated192. This is offset by the frequent sideeffects of such therapy (barotraumas in 1 to 2%, transientlung and eye damage in 15 to 20% of treatment cases)and the as yet far from convincing data on the treatmentof diabetic foot syndrome with hyperbaric oxygen(HBO)193.

A small randomised study in patients with, mostly neuro-pathic ulcers showed no effect on the reduction insize and colonisation of the ulcerations during a 14-daytreatment cycle. The healing rate was even lower inthe treatment group194. Another study in 1996 concludedthat HBO therapy in patients with diabetic foot synd-rome contributes not only to a significant increase intranscutaneous partial oxygen pressure (TCPO2), but alsoto a significant reduction in the number of major ampu-tations required (8.6% versus 33% without HBOtherapy)192. On careful analysis of the data, however, itbecame apparent that only one of three amputatedpatients in the treated group had amputation without pre-vious revascularisation, whereas in the control groupthis was the case in 7 out of 11 patients. The contributionof HBO therapy to reducing the number of amputationsthus remains questionable195.

A consensus conference on the subject in 1998 came tothe following conclusion:

1. The effect of hyperbaric oxygen therapy for radiationinduced wounds appears proven and there aregood data for osteomyelitis and soft tissue infection inanimal models and non-diabetics.

2. There are still no large randomised studies for diabeticfoot syndrome.

3. Ulcerations of Wagner grade 3 to 5 treated unsuccess-fully by standard methods in multidisciplinaryestablishments and for which an amputation is immi-nent may be considered for such treatment.

4. Careful follow-up of patients for diabetic retinopathy isnecessary.

78

5. Cost-effectiveness, quality of life and the endpoints oflimb preservation, duration of hospitalisation andhealing rate must be determined in the studies to beperformed196.

Use of growth factors and bio-engineered tissues

As has already been mentioned, deficits in immuno-competence play a significant role in the patho-physio-logy of wound healing disorders in the diabetic foot.In immunosuppressed patients suffering for examplefrom neutropenia as a result of chemotherapy, treat-ment with granulocyte-stimulating factor (G-CSF) hasbecome established. Studies have also recently beenconducted into the efficacy of these products in immuno-suppressant diseases without neutropenia. A studyalong these lines in patients with diabetic foot syndromefound an ulcer healing rate within 7 days of 21% versus0% with placebo as evidence of a supportive effectof such therapy on wound healing145. This isolated result,however, is a matter of dispute197.

Treatment with growth factors and bio-engineeredtissues has come to the fore in the last years. While aclinical study with fibroblast growth factor (bFGF)showed no advantage over standard therapy198, studieswith recombinant platelet derived growth factor(rhPDGF-BB, Regranex®, for example, revealed signifi-cantly improved healing rates and a faster reductionin wound diameter than with conventional wound treat-ment during a 20-week observation period199. Pre-liminary clinical results of the treatment of diabetic footwounds with bio-engineered tissues (Dermagraft®)were published in 1998. Dermagraft® consists of neonatal,dermal fibroblasts that are cultured in vitro in a bio-absorbable mesh. A viable, metabolically active tissue isproduced containing matrix proteins and cytokines.After application to diabetic foot ulcers once a week, ahealing rate of 50% was obtained within 12 weeksas compared to 8% in the reference group. During a14-month follow-up observation period, no patient in theDermagraft® group suffered a relapse. One explanationfor this might be found in the more flexible replacementtissue compared to traditional scar tissue.

In a follow-up study in six patients with “poorly-healingulcers” (mean duration of 43 weeks), 50% werehealed within 12 weeks. As a result of the acceleratedhealing and the lower tendency to relapse, treatment

79

Use of fly larvae (maggots)following the exhaustion ofall conservative and operativepossibilities and the imminentloss of an extremity

with Dermagraft® is regarded as cost-effective despitethe high costs of the product200.

While the results of studies on wound treatment withindividual growth factors in diabetic foot syndrome havebeen unconvincing, treatment involving products witha more complex composition of growth factors or withbio-engineered tissues offer interesting new prospects inproblem patients. Treatment with growth factors is notyet considered standard.

Biomechanical wound treatment

Biomechanical wound treatment (BMT) has in someinstitutes acquired a certain value recently as a supple-mentary measure in the therapy of chronic wounds.

Described for the first time in 1931, treatment with flylarvae (maggots) was a commonly used form of therapyin the treatment of infected skin injuries in the 1930sand 1940s in the USA. With the introduction of antibiotictherapy, this method of treatment was to a large extent

80

forgotten before undergoing a resurgence of interestin the 1980s in the USA and since the mid-1990s in GreatBritain202.

The mechanism of action by which the larvae of Lucilliaserricata (greenbottle fly) contribute to the cleaningand healing of necrotically coated or infected woundshas yet to be fully elucidated. The production of anantibiotic-like agent (also effective against micro-organis-ms resistant to conventional antibiotics), the presenceof growth factors in the larval secretion, the destruction ofbacteria by absorption and a change in the pH valueof the wound are postulated201. The provision of full anddetailed information to the patient and an explanationof the principle of therapy are essential. Surprisingly,problems of acceptance are occasionally to be foundless on the part of the patient than on that of medicalstaff202. This method is being used following exhaustionof conventional treatment procedures, as is the casein our hospital. In future, earlier use might mean fasterwound healing and the avoidance of the need forsystemic antibiotic treatment201.

Similarly, positive results are reported from individualcentres with the use of leeches (Hirudo medicinalis)in amputation surgery. Because of their local anti-in-flammatory and antithrombotic effect due to the forma-tion of hirudin, they are used in areas of criticallyimpaired circulation or in the development of hematoma.Very peripheral borderline zone amputations even inischaemic limbs should therefore be possible with goodresults203.

81

Tertiary prevention of thediabetic foot syndrome

Patients with DFS remain extremely high-risk patientsthroughout their life. Their education must includeinformation about what to do in the event of an injuryor impending amputation in addition to preventivefoot care aspects. Regular aftercare in special insti-tutions considerably reduces the risk of recurrence oflesions and subsequent amputations in thesepatients. Successful tertiary prevention must also in-clude risk-centred and phase-adapted shoe provisionfor patients and the organisation of injury-free, profes-sional foot care for those affected.

Effects of educating risk patients

Although value has been placed on the education ofdiabetics since the beginning of the insulin era, educa-tion was not considered an essential part of the treat-ment of diabetics insofar as there was no convincingevidence of its therapeutic efficacy. Preventive foot careprogrammes in which patient education representedan important component were among the first to show aclear benefit in this respect.

A diabetes programme was instituted in California asearly as 1969, involving educational measures anda telephone hotline. In Los Angeles the number of weeklyattendances for severe foot problems decreased from320 to 40204. Assal in Geneva found a complete lack ofany previous information about preventive or early treat-ment measures in 22 of 23 lower-leg amputated patients,whereas all eleven patients in whom surgery of the footarea had sufficed had received previous education.These were not controlled studies, but extensive pro-grammes involving different treatment approaches,including educational input. The contribution of the edu-cational components to the success of treatmentwas therefore difficult to distinguish from the improvedmedical care. However, further data about the import-ance of educational measures were obtained fromstudies which identified 40% of hospital admissions fordiabetic foot problems as the consequence of psycho-logical problems or inadequate information205.

82

In the late 1980s, a series of studies were carried out,firstly to establish the effect of patient educationalone and secondly to compare different types of foottraining programmes in terms of efficacy206.

The effect of a simple one-hour education programmewas examined in a prospective study in which the trainedgroup were shown slides of foot lesions in diabetics.After one year, the incidence of ulcers and the amputa-tion rate in the control group without any educationwas in each case three times higher than in the trainedgroup207. Comparing a straightforward lecture with apresentation involving practical exercises, the latter formof education showed a marked improvement in theshort term. There was improvement in the patients’ know-ledge and induction of behavioural changes, particularlyin nail care and daily foot inspections208. Simple educa-tional measures involving a single hour of instructionabout the foot, was compared to instruction spread overfour weeks with 11/2 to 21/2 hours’ instruction per weekand involving a chiropodist and a psychologist. The lattermethod had a sustained effect on patients’ behaviour,as well as increasing their knowledge. The number offoot problems that occurred fell markedly and the routineperformance of the patient’s own foot care and compli-ance with advice to consider professional foot care wereobserved much more often in the intervention group209.

Patient education should be simple, relevant andconsistent (the same verbal and written statements) andrepeat the central message. The simplicity of relevanttraining measures cannot be emphasised enough sincemany of the patients who develop foot problems arenon medical people who will not be helped by confusingvocabulary and complicated training programmes.Training programmes must take account of the socialbackground and the level of education of the patientsconcerned. A problem-oriented approach should beadopted and the patient should experience the urgentneed of having to know certain things, rather than simplyhaving the feeling of being forced to learn.

83

The aim and form of training should be tailored to thepatient and their requirements, because educationis only successful if it manages to change habits andpatterns of behaviour. Particularly in elderly peoplewho are often no longer capable of undertaking simplefoot inspections on their own. Partners, relatives orcarers should be included in the training. Finally, intensi-ve foot education should be directed towards specifictarget groups most at risk. The “over-education” ofhealthy diabetics may in the worst case even provecounterproductive210.

Evidence for the lack of education of affected patients isnot difficult to find: 25% of all type 1 and 50% of all type 2diabetics do not consider the loss of sensation in thelower limb a consequence of diabetes mellitus. Onlyabout 30% of all foot ulcer patients consider themselvesat risk of foot injuries and a similar small number haveever received information about foot and nail care beforesuffering their lesion211. Risk conditions, such asdiabetic neuropathy or arterial occlusive disease whichincrease the risk of amputation by 40% and 160%respectively compared with healthy subjects, do notresult in the increased prescription of foot care or theprovision of more intensive education for these patientsby their doctors. Only the presence of a foot injury oreven a prior amputation (11-fold increased risk of furtheramputation!!) mean that these patients receive moreintensive medical care212. Non-standardised treatment isoften the cause of a dramatic deterioration in the footdisorders in diabetics as lack of care on the part of thepatient213. Education must therefore be directed equallyto members of the medical professions (doctors, nursingstaff, physiotherapist, occupational therapist) and topatients and their relatives. The recognition of an “at riskfoot” and of early signs of pathological changes in thefeet of diabetics are the most important responsibilities inthe outpatient management of diabetic foot patients.The greatest barrier to this is a logistical one, namely thatof giving the patients the opportunity and regularlyencouraging them on their visit to the doctor to take offtheir shoes and stockings. Abnormal foot findings weredetected in only 20% of patients who wore shoes andstockings on their visit to the doctor. In contrast, 60% ofexisting foot problems were detected in patients whopresented themselves barefoot to their doctor. A footexamination is an extremely effective, but unfortunatelymuch too infrequently used preventive measure. In aNew Zealand study, lesions (ulcers, foot injuries) orpredisposing changes (fungal infections, maceration or

84

callus formation) were found in 50% of a group ofunselected diabetics. Only 40% of patients with existingblisters or foot ulcerations had undergone a footexamination in the 12 months prior to this examination214.

In addition to the provision of information to the patientabout the risk to their feet and the principles of properfoot care, educational measures for high-risk patientsmust include information about the correct action to takewhen foot injuries occur and how to react if the doctorrecommends amputation of a limb. No amputation indiabetics should occur today without a full circulatoryexamination (including angiography of the foot arteries).Patients should always be encouraged to obtaina second opinion before a planned amputation, wherepossible from a specialised centre215.

Importance of professional foot care

Foot care in diabetics is of particular importance, butalso requires particular knowledge and skills. Treatmenterrors can have serious consequences. Between13%216 and 30%217 of all foot lesions are related to footinjuries (either self inflicted by the patient or by pro-fessional chiropodists). Inadequate foot care or poorhygiene also contributes greatly. The use of keratolytics(products that remove horny skin), incorrect or wronglyused foot care instruments (tweezers, scissors, razorblades, “special tools” such as callosity files), andexcessively long or hot foot baths are possible causes offoot care related lesions.

Appropriate foot care treatment includes:1. Care of callus2. Removal of clavi (corns)3. Care of interdigital spaces4. Treatment of fissures, macerations and fungal

diseases5. Nail care and the careful correction of nail deformities.

The detection of pathological foot changes and theinspection of the patient’s footwear and stockingscan also be undertaken by chiropodists following theappropriate training.

85

The treatment of an ingrowing toenail (unguis incarna-tus), which is traditionally done surgically for exampleby means of wedge excision (Emmert-plasty) canaccording to a more recent study be successfully treatedconservatively by means of packing, pressure reliefand, where necessary, antibiotics. Surgical operationson the diabetic foot are associated with an increased riskof development of gangrene218.

In the USA and Great Britain well-trained foot carespecialists (podiatrists or chiropodists) have taken over alarge part of the management of diabetic foot patients.Similarly in Denmark the amputation rates were reducedby 30% between 1981 and 1989 as a result of the furthertraining of 450 chiropodists for the qualified treatment ofdiabetics. In contrast, in Germany in 1994 the Federationof German Physicians and Insurance Funds (BdÄK)excluded medical foot care from compulsory reimburse-ment by the regulatory health insurance funds. Thisprocedure was justified on the grounds firstly that footcare is a general measure of body care and hygiene andthus not a compulsory service of the health insurancefunds, and secondly on the grounds of the inadequatequality of medical foot care, without defining this further.According to a ruling of the Düsseldorf County Courtof 1997, not to exempt patients with foot diseases (e.g.with diabetic foot syndrome) from this regulation isillegal and hence void216.

It is true that medical foot care in Germany has not beenlegally regulated to date. Schools of podology with astructured, two-year training course have been set up inseveral German cities. Also, the establishment by theGerman Diabetes Society (DDG) for a transitional periodof a syllabus for qualification as a DDG chiropodistshould provide qualified foot care for diabetics through-out the whole of Germany as soon as possible.

It has recently been demonstrated that such regulartreatment not only reduces the risk of relapse, butalso substantially decreases treatment costs for footproblems216. Fifty-one patients (48 of whom had aprevious foot ulcer) received foot care treatment atmonthly intervals from a specially trained and qualifiednurse working in co-operation with a diabetes out-patient unit. The relapse rate was reduced to 8% peryear with the simultaneous provision of protectiveshoes. Instead of 30 patients admitted the previous year,

86

Pressure points with bruisingon the back of the feetfollowing the use of diabetesadapted insoles withinsufficiently deep footwear:the consequence of super-ficial knowledge in the patientand therapist

hospitalisation due to foot problems occurred in only7 patients. Before the introduction of professional footcare, 30% of patients had performed their foot carethemselves, half of whom had occasionally injuredthemselves in the process. The costs generated by footproblems were reduced by 80% as a result of thismeasure.

It seems particularly unlikely in elderly people that self-administered foot care can prevent the occurrenceof foot injuries. In a study of diabetics over 75-years-old,only 14% were able to inspect the sole of their ownfeet and more than 50% had problems with nail care.

The regular implementation of professional foot care forthis age group in particular will definitely have a moreeffective preventive result than thorough training of thepatients219.

87

Off-the-shelf, diabetes-adapted protective shoe withsole stiffening, a rockersole and raised toe room(Buratto company)

Provision of adapted footwear for diabetics

Between 28%78 and 55%79 of all foot lesions in diabeticsare related to footwear. In principle, shoes serve thesame purposes in diabetics and non-diabetics: they areworn for pleasure and for reasons of fashion, but whatis least firmly established in people’s minds is thatthey serve to protect the feet. Some people also use (ormisuse) shoes to hide changes in the foot. Medicalfunctionality is therefore only one of a number of aspectsof footwear. To reduce the importance of shoes to thispurely functional aspect or even to the subsidiary aspectof the protection of the diabetic foot against any form oftrauma is often difficult for the patient to understand andcauses the carer difficulties in dealing with thesepatients220.

It is only in recent years that there has been increasingrecognition of the importance of suitable footwear fordiabetics . There are now results of clinical case controlstudies on the prevention of relapse of foot ulcer compar-ing industrially produced shoes, off-the-shelf shoes(cost of about 200 EUR per pair) and customised ortho-paedic shoes (850 EUR per pair)221, 222, 223, 224, 225. Accord-ing to these studies, the relapse rate as a result ofstage-specific shoe provision can be reduced to about25% after one year and approximately 40% after twoyears.

This effect is even more apparent from an analysis ofthe prevention of shoe-related relapses following an initiallesion due to footwear. From this viewpoint, protectivefootwear saves 86% of patients from a relapse if theshoes are worn sufficiently long every day over a period

88

of two years78. The occasional wearing of normal shoes(27%), an incongruity between foot shape andcustomised shoe in the presence of gross deformities(27%) and hard toecaps are the reasons for furtherlesions despite specialist shoe provision226.

The basic features of diabetes-adapted footwear dateback to the work of Tovey in 198420. He suggested alow heel to prevent increased pressure on the forefoot,a broad forefoot without stiffness in the toe area andsufficient space to be able to take an elastic insole areamong the basic characteristics. In addition, high-qualitysoft leather should be used for the uppers and internalstitches should be avoided. To reduce plantar pressure,a sole stiffening plate with a rocker sole are amongthe design features of suitable protective shoes for dia-betics224. There is a 40–50% reduction in pressure in thesole area with such shoes227, 228 which have appropriatemultilayered insoles compared to normal shoes (60%reduction of presure as compared to walking barefoot228). Specially padded stockings can also reduce thepressure load by up to 30%, as well as reducing theeffect of shear forces229,230. Sufficiently deep runningshoes are considered by some authors to be the minimalacceptable option in the absence of deformities untilthe permanent protective shoe is finished or if the patientrefuses specialist shoe provision227, 231, 232. This type ofprovision reduces the plantar pressure load by 30–45%.

The fact that relapses cannot be avoided in a quarter ofpatients annually is due to various reasons. Firstly,patient acceptance of diabetes-adapted footwear is lowat 22%233–63%234. Although not all patients approvedthe appearance of their customised orthopaedic shoes,51 out of 85 foot outpatients were wearing their custo-mised shoes at a random inspection. Patients who dis-played a higher degree of compliance were older andmore frequently had previous amputations than the lesscompliant patients235. Patient participation in the designof the shoes and a broader range in terms of shapes andcolours would possibly increase the frequency withwhich such footwear was worn. More intensive informa-tion, directed at patients with shoe-related lesions, the

89

Blueprint of a slightly altereddiabetic foot: by positioningtheir own shoes over the top,the patient was able to seethe incongruity between shoesize and foot size

provision of a sufficient number of suitable pairs of shoesand the additional prescription of slippers could alsocontribute to reducing relapses. Twenty-two percent ofpatients with foot ulcers in a Southern German diabetesclinic79 and a similar percentage of patients in our ownoutpatient foot department were not prescribedprotective shoes in 1994 and 199578. Regular inspectionof the shoes and insoles, particularly in the periodafter the prescription, and the consistent improvement ofdeficiencies are essential for quality assurance andavoidance of ulcers.

A further obstacle to the widespread use of therapeuticfootwear became apparent in an American study. Only6% of all doctors who were informed about the possibilityof prescribing protective footwear with reimbursementby insurance companies prescribed such shoes inthe following three years (one in 10 orthopaedic surgeons,one in 21 internists and only one in 53 general practi-tioners or family doctors). Fiftynine percent of the patientsprovided with footwear had a previous history of footulcer in this study and 25% of patients had previousamputation236.

90

Result of computer-assistedplantar foot pressure measure-ment in a patient with halluxrigidus and increased footpressures in the area of themetatarsus with diabeticosteoarthopathy (Fastscanmeasurement system,Megascan company)

Compared with studies of the benefit of specialisedshoe provision in the prevention of relapses, the data onshoe provision for prophylaxis in patients withoutprevious foot injuries is less extensive. In a German studyover a 2-year period, only one in 21 patients withouta previous foot lesion suffered a foot injury following theprovision of protective shoes226, and two out of 49patients in another study237. Predictors of the occurrenceof foot lesions in this patient group are the purchaseof new shoes in the six months prior to the occurrence ofthe ulcer and wearing the wrong size of shoes238. In 80%of patients from a diabetic population, among whom 27%had already suffered a foot ulcer, the feet were nevermeasured when buying shoes212. Recent studies on thesubject have shown that the feet of diabetics withneuropathy match the normal size in terms of length.

In terms of width, the normal shoe width G is too narrowfor 65 - 95% of patients. Even the next width up,extra G (extra large), was inadequate for 44%–84% ofpatients239. According to another study, only about20% of diabetic patients were able to use normal foot-wear, and only to a limited extent. About 60% of patientswere able to wear off-the-shelf protective shoes, whilefor 22% of male diabetics and 13% of female diabetics,a proper fit was only possible with hand-made customis-ed shoes240. Although clinically tested off-the-shelfprotective shoes are currently specifically excluded fromcompulsory benefits from the health insurance funds,a large proportion of patients could be supplied cheaply

91

with such footwear to match the stage of their condition.Only patients with gross deformities or who have al-ready undergone amputations of part of the foot requirethe more expensive hand-made customised footwear.The value of computer-assisted foot pressure measure-ment procedures in the production and follow-up ofspecialised shoe provision for diabetics cannot be con-clusively established at the present time.

92

Footwear provision for the diabetic foot – Classification by risk groups

Ia: Diabetes mellitus without PNP/AOD*:Off-the-shelf shoe

Ib: As above, with foot deformity:Orthopaedic inserts, shoe devices

IIa: Diabetes mellitus with PNP/AOD:Suitable off-the-shelf protective shoe

Minimal criteria for a shoe of this kindinclude sufficient toe room, sufficientwidth, no stitches in front part of shoe,soft leather, removable insole with softcushioning and reduction of pressurepoints by at least 30% in the metatarsalregion. No hard toe caps. The efficacyof off-the-shelf protective shoes – withor without individually designed insoles– needs to be demonstrated in studies.

IIb: As above with foot deformity:Off-the-shelf protective shoe whereappropriate; in the event of specific footdeformities, shoe devices and/orindividual diabetes-specific insoles,possibly custom-made shoes

Inspection of insoles and regularrenewal

III. Foot as II and status following ulcer:Shoe provision as for II.

* PNP = Polyneuropathy AOD = Arterial Occlusive Disease

IV. Foot as II and high grade deformityor osteoarthropathy:

Custom-made shoes, orthoses, innershoes

V. Status following partial footamputations:As IV, plus toe and forefoot replacementprostheses.

The effectiveness of custom-madeshoes with individually designedinsoles needs to be demonstrated instudies since at present there is nostandardisation of materials and designof custom-made shoes for the diabeticfoot.

VI. Footwear provision in acute ulcers,etc.:Various relief shoes and pressure-relieving ortheses are used herein plantar ulcers and bandage shoes innon-plantar ulcers.

The effectiveness of the various pres-sure-relieving and therapeutic shoesalso needs to be demonstrated instudies.

Erich Gromotka, orthopaedic shoemakerGeorg Seeßle, orthopaedic shoemakerJürgen Stumpf, orthopaedic shoemakerKarl Türk, orthopaedic shoemakerDr. Bettina BornDr. Christoph MetzgerDr. Maximilian Spraul

Working party„Quality criteria and evaluation of shoeprovision for the diabetic foot“

93

Structures for screening, treatment and aftercare ofpatients with diabetic foot syndrome

The financial burden and the human suffering caused bydiabetic foot syndrome need not be accepted asinevitable. Numerous studies in the past few years haveshown that more than 50% of all amputations in diabeticsare avoidable if the following procedures are appliedsystematically:

– Regular inspection of feet and footwear of diabeticsat each visit to the doctor

– Preventive foot care and shoe provision in high-riskpatients and additional education

– Use of multifactorial and multidisciplinary treatmentconcepts in the case of foot lesions

– Early diagnosis and appropriate treatment ofperipheral circulatory disorders in diabetics

– On-going aftercare of patients with previous footulcerations or prior amputations

– Strict adherence to defined indications foramputation241 and establishment of amputationregisters

The management of Diabetic Foot Syndrome in non-specialist German hospitals at the beginning of the1990s unfortunately revealed a different, somewhatgloomier picture. Almost 50% of the foot lesions treatedthere culminated in an amputation and every secondamputation was a major amputation. In patients with anarterial occlusive disease only, the rate of major amputa-tions was 56%. In patients with combined neurologicaland ischaemic findings, the amputation rate was 38%,and in patients with purely neuropathic foot lesions, 27%of treatments ended in amputation. Inappropriate con-servative treatment concepts and complete ignorance ofvascular surgical treatment options were the reasonsfor the frightening amputation statistics in the studyquoted242. If patients in whom an indication was estab-lished for minor or major amputation were transferredto a specialist centre (mostly on their own initiative), 83%of impending limb amputations and 79% of scheduledfoot amputations were avoided as a result of the exploita-tion of all the therapeutic options243.

94

The fact that things could be different had beenimpressively demonstrated many years ago: In the 1970sDavidson in Atlanta had demonstrated the possibilitiesof reducing amputations in diabetics through a teamconcept with risk screening, education and systematicaftercare of the patient21. The amputation figures halvedbetween 1973 and 1980 after the introduction of thesemeasures (from 13.3 to 6.7 amputations/1000 patients/year). A total of 555 amputations were avoided overthis period. Similar figures were reported in the followingyears from Switzerland, England221,224, Scandanavia245,246,Italy247 and Germany24,248. The healing rates for diabeticfoot lesions reported from such centres were 72%to 80% in ischaemic lesions and 86% to 95% in neuro-pathically infected foot ulcers221,249. Between 1994and 1998 in our own outpatient diabetic foot departmentat the Marienkrankenhaus, (Soest/Germany) majoramputations were entirely avoided in purely neuropathi-cally induced foot lesions. In purely ischaemic lesions a40% reduction in all types of amputation was obtained250.

The establishment of outpatient diabetic foot depart-ments in specialised clinics, however, not only resultsin a marked reduction in the number of amputationsnecessary and consequently an improvement in thequality of life of those affected, but also produces con-siderable cost savings. The need for inpatient treat-ment can be reduced from on average about 40 days242

to approximately 20 days through the possibility offollow-up outpatient care24, i.e. it can be shortened byabout three weeks. Inpatient hospital treatment caneven be totally avoided in a high proportion of purelyneuropathically related lesions23.

The leg preservation rate with the maximum exploitationof vascular surgical possibilities (43% crural and 12%pedal vascular reconstructions) for patients with criticallimb ischaemia is 85% after two years and almost ashigh for patients with neuropathic lesions complicated bya serious infection. If vascular reconstruction is notpossible in patients with ischaemic lesions, the limb pre-servation rate is reduced to 17% after two years249.

95

Not only have these outpatient diabetic foot departmentsdemonstrated their value in terms of improved prognosisfor manifest foot lesions, but also their efficacy in theprevention of lesions in previously ulcer-free high-riskpatients is now documented. Over a three-year period,patients who did not receive regular care from an out-patient foot department suffered a foot ulcer 24 timesmore often than patients who received constant attentionfrom such a department. A lack of patient compliance(in this case defined as a failure to attend less than halfthe arranged appointments) increased the probabilityof ulcer 54-fold and the risk of amputation 20-fold for thewhole population, including patients with previous footlesions251.

Patients with diabetic foot syndrome remain high-riskpatients throughout their life. Despite structuredaftercare, about a third of patients suffer a first relapsewithin one year of the healing of an initial lesion78,37, whileafter two years the figures are between 40% and 50%of patients78,79,37. After five years seven out of ten patientshave suffered a recurrence of the lesion37. In previouslyamputated patients the annual relapse risk is reported as85%252. If such patients are not continuously treatedby a specialist establishment after the healing of a footinjury, their risk of amputation in the event of a relapseis almost 70%. If they continue to be treated by an out-patient foot department, this risk falls to about 20%253.In one of our own studies in 30 patients who suffered arelapse despite receiving care from an outpatientdiabetic foot department, amputations were completelyavoided after a second lesion. The need for hospitali-sation in association with a recurrent lesion regressed to7%, compared to 73% with the first lesion, and theduration of healing was reduced from 64 to 29 days254.

Structured care therefore shows a positive effect on theavoidance of foot lesions in high risk patients, thecourse manifest foot injuries take, and the prognosis incase of recurrence.

96

Levels of care for the support of patients with diabetic foot syndrome (modifiedby Reike)

Target group Activity

Medical footcare practice(Chiropodist/DDG, GermanDiabetesSociety)

Generalpractitioner

Practitionerwithspecialisationin diabetes

Outpatientdiabeticfoot clinic(hospitalbased)

DFS inpatientunit

Patients at risk of footlesions

All diabeticsPatients at risk of footlesions

Patients with a healed footlesion

Diabetics with Wagnerstage 2 and 3 foot lesionsDiabetics with footlesions and wound healingdisordersDiabetics with osteo-arthropathy (acute/chronicCharcot’s foot)

Diabetics with footlesions and wound healingdisordersDiabetics with criticalischaemiaDiabetics with acuteosteoarthropathy

Atraumatic removal of callositiesSkin and nail careAdvice to patients

Primary/secondary preventionMetabolic control/advice

Screening of risk patientsClinical follow-up examination anddiagnosis. Basic instrumental exami-nation. Footwear inspection. Whereappropriate, microbiology andstructured local wound treatment inWagner stage 1 (possibly 2)

Neurological, angiological andradiological diagnosis. Microbiologicaldiagnosis.Interaction with otherspecialist disciplines. Structured localwound management, where necessarywith establishment of a treatment planfor GP care. Co-operation with ortho-paedic technician and orthopaedicshoemaker. Referral to outpatient careservices. Education of (high-) riskpatients.

General medical care of otherconcurrent diseases. Structured localwound care. Near-normal bloodglucose metabolic control (ICT).Angiological diagnosis, therapy ifnecessary (PTA). Co-operation withother specialist departments (vascularsurgery, surgery, radiology). Co-operation with orthopaedic technicianand orthopaedic shoemaker.Referral to outpatient care services.

97

In order to allow successful specialist treatment ofpatients with diabetic foot lesions at an early stage, allthe existing centres must co-operate to streamlinetreatment. In a current Swedish study, there was aninterval of between 31 and 189 days between the firstpresentation of a foot injury at the general practitioner’sand the institution of care by an outpatient foot depart-ment. Antibiotic treatment was instituted in a primary caresetting in 44% of patients, but additional measures,such as pressure relief, were implemented in only 8% ofcases255. In our own prospective study, the intervalbetween the occurrence of the lesion and the first pre-sentation at the outpatient diabetic foot departmentin 153 patients without any prior information about theprocedure to be followed in the event of foot problemswas on average 71 days. However in 62 patients withprevious education or contact with the outpatient footdepartment for a previous lesion, the interval was13 days. The corresponding amputation rates were 24%and 10%, respectively256.

The role of the family doctor might be:1. The identification of patients at risk of foot lesions2. The provision of basic information to these patients3. The implementation of preventive measures4. The regular inspection of foot status

Minor foot lesions can be managed in a diabetes clinicand, in emergency cases, in specialised outpatientdiabetic foot departments. The complete diagnosis andtreatment of more complex foot lesions should also beundertaken there, with the involvement of diabetologists,surgeons, vascular surgeons, chiropodists, orthopaedicshoemakers and interventional radiologists. Emergencyfacilities and the presence of a special foot unit withappropriately trained staff should be among the featuresof such specialised establishments. Problem-centredinterdisciplinary visits can further improve the efficiencyof such establishments.

98

Successful co-operation in a network of this kind requiresseamless transitions (frequently complicated by the strictseparation of outpatient and inpatient structures inGermany), the absence of fear of contact and thepresence and implementation of guidelines which arevalid for all participants. A consensus paper in thisrespect on the diagnosis and treatment of the diabeticfoot was published for the first time in May 1999 by theInternational Working Group on the Diabetic Foot.

The diabetic foot: a global problem

The prevalence of diabetes world-wide, which affectedapproximately 135 million patients in 1996, is predictedto grow to 300 million patients by the year 2025 on thebasis of increasing life expectancy throughout the world,the change in dietary habits and the increase in theproportion of obese patients. In particular, countries withlittle or no infrastructure and no standards of foot care,will experience the most dramatic increases in type 2diabetics. Thus, in the year 2025 India is predicted tohave 57 million diabetics and China 38 million. In Centraland Southern African countries, the number is estimatedto grow from 3 million at present to 8 million, representingan increase of 185%2. Although the pathogenesis ofdiabetic foot problems is probably the same everywherein the world, the clinical manifestations and the problemsobserved differ according to local conditions andsociocultural features between the distinct countries andthe various geographic regions.

In Western European countries, the distribution ofrisk conditions (arterial occlusive disease and diabeticsensorimotor neuropathy) is very similar to that foundinternationally257. Also the treatment results essentiallyreveal no differences between Central European andNorth American centres258. The conditions in other partsof the world are quite different as a result of specificepidemiological factors and the features of the relevanthealthcare systems.

99

Manifestations of diabetic footsyndrome in India:

a) Callus formation on thedorsum of the foot in a Moslemdiabetic patient – a resultof the typical kneeling prayingposition with crossed feet

b) Burn in the area of the rearof the foot as a result ofplacing the naked foot on thehot exhaust pipe of amotorbike (both pictures werekindly provided by Dr. V.Viswanathan, Chennai, India)

In Eastern Europe, specialist centres for the treatment ofthe diabetic foot are rare. In many places amputation isstill considered the standard. As a result of twinningprogrammes with Western European countries, structuralimprovements are gradually occurring in certain regions.In South America, where the prevalence of diabetes ismore than 6%, the establishment of institutions has so faronly been observed in Costa Rica, Mexico and Brazil. Insome North African countries more than 10% of thepopulation are diabetics, up to 12% of patients with footulcerations are found among hospital inpatients and 7%of diabetics have had previous amputation. In Australiaprogrammes involving foot care in diabetics have alreadybeen implemented countrywide. In some tropicalcountries, the co-existence of diabetes mellitus andleprosy has resulted in a particularly high occurrence ofpatients with a potential risk of occurrence of footlesions259. In addition, a relatively high proportion of foot

100

(and hand) infections is found here in diabeticswithout the conventional risk conditions, such as arterialocclusive disease and diabetic neuropathy260,261.

On the basis of our own study (613 patients), the follow-ing essential differences were observed in the pre-senting conditions of diabetic foot syndrome between anindustrial country (Germany) and two developingcountries (Tanzania and India). In developing countriesthere is a far smaller proportion of patients with arterialocclusive disease, because abuse of nicotine is lesscommon. The patients are much younger and the dura-tion of diabetes is shorter. Shoe-related lesions werefound in the developing countries in only 5 to 6% ofcases, as opposed to 27% in the industrial nations. Thepresence of a diabetic neuropathy in patients withdiabetic foot syndrome, however, was equally high inboth populations, at about 80%262.

The situation in some African countries is characterisedby the high proportion of illiteracy among foot patientsand the more difficult conditions for the provision ofinformation and education. In some cultural environmentsamputation of a limb is considered to be more seriousthan the loss of one’s own life261. This explains the highproportion of self-discharges by patients beforethe end of treatment from hospitals, especially in view ofa more than 50% amputation rate. Unusual manifesta-tions due to specific sociocultural conditions characte-rise the picture of the diabetic foot in India. In a countryin which 30% of people live below the poverty line,wearing shoes tends to be the exception rather than therule. Infections of fissures resulting from walking barefootare among the causes of diabetic foot problems in India,as are burns from the hot cobble stones of the Hindutemples where the faithful are strictly forbidden to wearshoes and pressure sites in the ankle region becauseof the particular praying position of the Moslems263. Ratbites of the toes of neuropathic patients264 are amongthe unusual presenting forms of diabetic foot syndromein India, as well as infections from tropical worms.

101

Summary and prospectsMore than half of all limb amputations are carried out inpatients with diabetes mellitus. In more than 70% ofcases, amputation is preceded by a foot ulcerprogressing to deep gangrenous infection. Most of theseulcers are caused by minor trauma, frequently as a resultof poorly fitting footwear or inadequate foot care.Sensorimotor diabetic neuropathy or a peripheral arterialocclusive disease of varying severity are in most casespresent as risk conditions predisposing to injury.

The continuous registration of amputations (amputationregisters, e.g. the Danish amputation register, North RhineChamber of Physicians Diabetology/Surgery QualityAssurance) can help to reduce amputation rates in dia-betics265. The DCCT study6 has shown that intensivetreatment of type 1 diabetics and optimised blood sugarcontrol can reduce the probability of diabetic neuropathyoccurring by 50%. However, as long as the avoidanceof secondary micro-angiopathic complications remains agoal for a majority of diabetics, the early identificationof risk conditions, the avoidance of lesions in high riskpatients and the structured treatment and aftercare ofulcer patients (and previous amputees) must be made apriority.

Key preconditions for improving the prognosis ofdiabetics with foot lesions are:1. Regular screening of diabetics for impaired nerve

function and inadequate circulation2. Problem-centred patient education3. Regular foot care and the supply of protective

footwear to those affected4. Structured and team-based care of patients with

active ulcerations

The specific recording of individual causes of injury andintegration of these findings in the risk-centred educationand aftercare of patients and relatives may help toreduce the emergence of recurrent lesions and hence therisk of amputation still further78,266.

102

The implementation of prevention and treatmentstrategies has been shown to help avoid more than 50%of amputations in diabetics.

According to Swedish estimates, halving the amputationrate would reduce the costs of treatment of diabetic footproblems by about 20 to 40%267.

Although in the new millennium new treatment optionsmay facilitate the treatment of diabetic foot lesions, thecontinuing construction of suitable treatment establish-ments and their regional networking certainly cannotbe replaced. Extensive and structured treatment andaftercare of patients with diabetic foot syndrome inspecialised and quality assured institutions is necessaryto implement the requirements of the St. Vincent Declara-tion. The key to success for the development of appro-priate infrastructures to allow the creation of foot teamsfor problem patients lies in obtaining the necessarycontribution from insurance companies, as well as earlyregistration and targeted care of high risk patients.In view of the enormous expenditure on amputations indiabetics and the comparatively low costs of preventivemeasures in diabetic foot syndrome, it may be assumedthat such efforts will be associated with a favourablecost-benefit ratio.

Extensive knowledge alone remains ineffective. To contri-bute to successfull treatment, this knowledge must beapplied. In the form of behavioural changes in patientsand also in the professional groups treating them withinthe healthcare system. It is not the hope of new treatmentprocedures, but simply the consistent applicationof what is known, established and already possiblethat in the future will result in amputations becoming anexception and not the rule in patients with diabeticfoot syndrome.

103

Definitions andexplanationsAmputationResection of a part of a limb

Arterial occlusive diseasePresence of clinical signs such as the absence of footpulses, previous history of intermittent claudication,rest pain and/or abnormalities in non-invasive examina-tions indicating impaired or insufficient circulation

CellulitisPresence of swelling, redness and heat as evidence ofan inflammatory reaction, irrespective of origin

Charcot’s deformityResulting from Charcot’s disease or arthritis; also neuro-pathic arthritis - it is a rapid progressive degenerationin a joint which lacks position sense and protective pain

Chopart amputationAmputation through the talo-navicular joint

Deep infectionPresence of evidence of an abscess, septic arthritis orosteomyelitis

DébridementRemoval of dead tissue

Deep ulcerLesion affecting the whole thickness of the skin andextending to the subcutis, possibly involving muscles,tendons, bones and joints at the same time

Diabetic foot syndromeInfection, ulceration and/or destruction of deeptissue associated with neurological abnormalities andvarious degrees of severity of arterial circulatorydisorders of the lower extremity

Diabetic neuropathyPresence of signs and/or symptoms of disordersof peripheral nerve function in patients with diabetesmellitus after the exclusion of other causes

104

Foot deformityStructural changes in the foot, such as the presence ofhammer toes, claw toes, hallux valgus, prominent meta-tarsals and conditions due to neuro-osteoarthropathy, aswell as surgery on the foot and amputations

Foot lesionBlister, erosion, cut or ulcer on the foot

GangreneProgressive necrosis of the skin and deeper structures(muscles, tendons, bones or joints) indicating irreversibledestruction, in which healing cannot be obtained withoutthe loss of part of the extremity

InfectionPenetration and proliferation of micro-organisms in bodytissue, which may be clinically insignificant or mayresult in local cell death, as a result of toxins, intracellularmicrobial proliferation or an immune response

Intermittent claudicationPain in the foot, thigh or calf which is increased on walk-ing and relieved on stopping, associated with evidenceof an arterial occlusive disease

Major amputationAny amputation above the ankle joint

Minor amputationAmputation at the level of the ankle joint or lower

NecrosisDead tissue, either dry or moist, regardless of the tissueaffected

Neuro-osteoarthropathyNon-infectious destruction of the bone or jointsassociated with a neuropathy

NeutropeniaRelative or absolute decrease in the number of neutro-philic leucocytes in the blood

OsteomyelitisInfection of the bone with involvement of the bonemarrow

105

Pirogoff amputationThe calcaneum is cut across so that the posterior 2 cmremain in the heel flap and this is attached to thelower end of the tibia, making a longer stump than in theSyme’s amputation

PolymicrobialInfections with more than one organism causing damage

Pressure reliefRelief of load-bearing areas of the foot through thesystematic use of crutches, wheelchairs, partial foot reliefshoes or other orthopaedic devices

Protective footwearFootwear of proven benefit in the prevention ofulcerations

Superficial infectionInfection of the skin without involvement of muscles,tendons, bones or joints

Superficial ulcerLesion affecting the whole thickness of the skin withoutextending to the subcutis

Syme’s amputationThe original level of amputation was through the anklejoint with the medial and lateral malleolus trimmed.The amputation has been modified to divide the tibia andfibula 1 cm above the joint line. In an emergency thepatient is able to stand and walk without the prosthesis

106

Abbreviations:ABI Ankle Brachial IndexADA American Diabetes AssociationAOD Arterial Occlusive DiseaseATR Achilles Tendon Reflex

bFGF b-Fibroblast Growth FactorBMT Biochemical Wound Therapy

CNS Central Nervous SystemCSII Continuous Subcutaneous Insulin InfusionCT Conventional Insulin TherapyCVA Cerebral Vascular Accident

DCCT Diabetes Control and Complication TrialDDG Deutsche Diabetes Gesellschaft (German

Diabetic Association)DFS Diabetic Foot SyndromeDNOAP Diabetic Neuropathic OsteoarthropathyDSA Digital Subtraction Angiography

ESR Erythrocyte Sedimentation RateEUR Euro

GAD Glutamic Acid DecarboxylaseGCSF Granulocytes Stimulating FactorGDM Gestational Diabetes Mellitus

HbA1c Haemoglobin Receptor A1 cHBO Hyperbaric Oxygen

ICA Islet Cell AntibodiesICT Intensified Conventional Insulin Therapy

MRI Magnetic Resonance Imaging

PDGF Platelet Derived Growth FactorPNP PolyneuropathyPNS Peripheral Nervous SystemPTA Percutaneous Transluminal Angioplasty

rhPDGF Recombinant Platelet Derived Growth Factor

TCPO2 Transcutaneous Partial Oxygen PressureTGF‚ Tissue Growth Factor ‚

UKPDS United Kindom Prospective Diabetes Study

V Volt

WHO World Health Organisation

107

Proposed further readingAndrew JM Boulton, H Connor, Peter R Cavanagh (Eds).The Foot in Diabetes, 3rd Edition. Wiley and Sons Ltd.,Chichester 2000.ISBN 0-471-48974-3

John H Bowker, Michael A Pfeifer (Eds). Levin andO’Neal’s The Diabetic Foot, 6th Edition. Mosby Inc.,St Louis 2001.ISBN 1-55664-471-x

Mike E Edmonds, Alethea VM Foster. Managing theDiabetic Foot.1st Edition, Blackwell Science, Oxford2000. ISBN 0-632-05583-9

Robert G Frykberg (Editor). The High Risk Foot in Diabe-tes Mellitus, 1st Edition. Churchill Livingstone Inc., 1991.ISBN 0-443-08665-6

William Jeffcoate, Rosamund MacFarlane. The DiabeticFoot – An illustrated guide to management, 1st Edition.Chapman & Hall Medical, 1995. ISBN 0-412-54410-5

Aristidis Veves, John M. Giurini, Frank W. Lo Gerfo (Ed.):The Diabetic Foot, Medical and Surgical Management,Humana Press, Totowa, New Jersey, 2002ISBN 0-89603-925-0

Acknowledgements for photographs:

David Gifford / Science Photo Library / Focus(Cover page)

Morbach, S. (P. 25–57 and P. 70–90)

Thanner GmbH (P. 50)

Viswanathan, V. (P. 99)

All other photographs from the PAUL HARTMANN AGarchive, Heidenheim

108

109

References1. Harris M. I.: Descriptive Epidemiology, In:Diabetes in America, 2nd edition, National Institu-tes of Health, National Institute of Diabetes andDigestive and Kidney Diseases, NIH PublicationNr. 95-1468, (1995), 1-13

2. King H., R. E. Aubert , W.H. Herman: GlobalBurden of Diabetes, 1995-2025, Diabetes Care,(September 1998), Vol. 21, Nr. 9, 1414 -1431

3. Hauner H.: Verbreitung des Diabetes mellitusin Deutschland, Dtsch. med. Wschr. (1998), 123,777-782

4. The Expert Commitee on the Diagnosis andClassification of Diabetes Mellitus: Reportof the Expert Committee on the Diagnosis andClassification of Diabetes Mellitus, DiabetesCare, (July 1997), Vol. 20, Nr. 7, 1183-1197

5. Seissler J., J. J. de Sonnaville, N. G.Morgenthaler: Immunological heterogeneity inType I diabetes: presence of destinct autoantibodypatterns in patients with acute onset and slowlyprogressive disease, Diabetologia (1998), Vol. 41,891-897

6. UK Prospective Diabetes Study Group: Intensi-ve blood-glucose control with sulphonylureasor insulin compared with conventional treatmentand risk of complications in patients with type 2diabetes (UKPDS 33), The Lancet, (September1998), Vol. 352, 837-853

7. The Diabetes Control and Complications TrialResearch Group: The effect of intensive treat-ment of diabetes on the development and pro-gression of long-term complications in insulin-dependent diabetes mellitus, The New EnglandJournal of Medicine, (September 1993), Vol. 329,Nr. 14, 977-986

8. UK Prospective Diabetes Study Group: Effect ofintensive blood-glucose control with metforminon complications in overweight patients with type 2diabetes (UKPDS 34), The Lancet, (September1998), Vol. 352, 854-865

9. Muggeo M.: Accelerated Complicationsin Type 2 Diabetes Mellitus: The Need for GreaterAwareness and Earlier Detection, DiabeticMedicine, (1998) 15 (Suppl. 4), 60-62

10. Harris M. I., R. Klein, T.A. Welborn et al.: Onsetof NIDDM Occurs at Least 4-7 Yr Before ClinicalDiagnosis, Diabetes Care, (July 1992), Vol. 15,Nr. 7, 815-819

11. UK Prospective Diabetes Study Group: Tightblood pressure control and risk of macrovascularand microvascular complications in type 2 dia-betes: UKPDS 38, BMJ, (September 1998), Vol.317, 703-713

12. Walsh C. H., N. G. Soler, M. G. Fitzgerald, etal.: Association of foot lesions and retinopathyin patients with newly diagnosed diabetes, TheLancet, (April 1975), 878-880

13. Ritz E., J. Lippert, C. Keller: Rapider Anstiegder Zahl niereninsuffizienter Typ-II-Diabetiker,Dtsch. med. Wschr. (1996), 121, 1247

14. Yamamoto M., G. Egusa, M. Okubo, et al.:Dissociation of Microangiopathy and Macroangio-pathy in Patients With Type 2 Diabetes, DiabetesCare, (September 1998), Vol. 21, Nr. 9, 1451-1454

15. CDC Diabetes Cost-Effectiveness StudyGroup: The Cost-effectiveness of Screening forType 2 Diabetes, JAMA, (November 1998),Vol. 280, Nr. 20, 1757-1763

16. Pryce T. D.: Perforating ulcers of both feetassociated with diabetes and ataxic symptoms,The Lancet (Juli 1887), 11-12

17. McKeown K. C.: History of the diabetic foot,The Foot, (1992), 2, 179-182

18. Joslin E. P.: The Menace of Diabetic Gangrene,The New England Journal of Medicine, (July 1934)16-20

19. Oakley W., R. C. F. Catterall, M. M. Martin:Aetiology and Management of Lesions of the Feetin Diabetes, British Medical Journal, (October1956), 953-957

20. Tovey F. I.: The Manufacture of DiabeticFootwear, Diabet Med, (1984), Vol.1, 69-71

21. Davidson J. K., M. Alogna, M. Goldsmith, et al.:Assessment of programme effectiveness at GradyMemorial Hospital - Atlanta, In: G. Skeiner,P.A. Lawrence (eds), Educating diabetic patients.Springer Verlag, New York (1989), 329-348

22. Assal J.-Ph., A. Albenau, B. Peter-Riesch, etal.: The cost of training a diabetic patient. Effectson prevention of amputation, Diabete & Meta-bolisme (1993), 19, 491-495

110

23. Kardorff B.: Ergebnisse einer integriertenambulanten und stationären internistischenBehandlung des „diabetischen Fußes“, PrävRehab (1992), Vol. 4, Nr. 1, 1-8

24. Hanfland J.: Welchen Beitrag leistet eineSpezial-Ambulanz bei der Behandlung von Patien-ten mit „diabetischem Fuß“?, medwelt (1987), 38,1405-1409

25. Diabetes Care and Research in Europe:The Saint Vincent Declaration, Diabetic Medicine(1990), 7, 360

26. Payne C.: Increased Frequency of DiabeticFoot Publications, Diabet Med (May 1997), 14 (5),407

27. Chantelau E.: Das Syndrom des „diabetischenFußes“, Zentralbl Chir, (1999), 124, Suppl 1, 6-11

28. Dahmen H.-G.: Das diabetische Fußsyndromund seine Risiken: Amputation, Behinderung,hohe Folgekosten, Gesundheitswesen, (1997), 59,566-568

29. Chantelau E., M. Spraul, M. Berger: Das Syn-drom des diabetischen Fußes – Neue Aspekte, In:W. Hepp, Der diabetische Fuß, BlackwellWissenschafts-Verlag Berlin, (1996), 8-15

30. Boulton A.J.M.: The Diabetic Foot: Neuropathicin Aetiology?, Diabetic Medicine (1990), 7,852-857

31. Young M.J., A.J.M. Boulton, A.F. Macleod, etal.: A muticentre study of the prevalence of dia-betic peripheral neuropahty in the United Kingdomhospital clinic population, Diabetologia (1993), 36,150-154

32. Cabezas-Cerrato J.: The prevalence ofclinical diabetic polyneuropathy in Spain: a studyin primary care and hospital clinic groups,Diabetologia (1998), 41, 1263-1269

33. Veves A., C. Manes, H. J. Murray, et al.: PainfulNeuropathy and Foot Ulceration in DiabeticPatients, Diabetes Care, (August 1993), Vol. 16,Nr. 8, 1187-1189

34. Stiegler H., S. Frey, E. Standl: Diagnostischeund therapeutische Überlegungen beim„diabetischen Fuß, Med Klin (1988) , 83, Nr.7,263-269

35. Borrsén B.,T. Bergenheim, F. Lithner: The epi-demiology of foot lesions in diabetic patients aged15-50 years, Diabetic Medicine, (1990), 7, 438-444

36. Küstner E., M. Giulini, M. Neese et al.: Epide-miologische Datenerhebung zum diabetischenFuß-Syndrom mit einer mobilen Untersuchungs-einheit in 14 Städten, Diabetes und Stoffwechsel,(1997), 6, Suppl. 1, 136

37. Apelqvist J., J. Larsson, C.-D. Agardh: Long-term prognosis for diabetic patients with footulcers, Journal of Internal Medicine (1993), 233,485-491

38. Pecoraro R.E., G.E. Reiber, E.M. Burgess:Pathways to diabetic limb amputation. Basis forprevention, Diabetes Care ( May 1990), 13 (5),513-521

39. Most R. S., Sinnock P.: The Epidemiology ofLower Extremity Amputations in DiabeticIndividuals, Diabetes Care, (January/February1983), 6, 87-91

40. Nelson R. G., D. M. Gohdes, J. E. Everhart,et al.: Lower-Extermity Amputaions in NIDDM, Dia-betes Care (January 1988), Vol. 11, Nr. 1, 8-16

41. Armstrong D. G., L. A. Lavery, W. H. vanHoutum, et al.: The Impact of Gender on Amputati-on, The Journal of Foot and Ankle Surgery (1997),36 (1), 66-69

42. Stiegler H., E. Standl, S. Frank, et al.: Failureof reducing lower extremity amputations in diabeticpatients: results of two subsequent populationbased surveys 1990 and 1995 in Germany, VASA(1998), 27, 10-14

43. Trautner C., B. Haastert, G. Giani, et al.:Incidence of Lower Limp Amputations and Dia-betes, Diabetes Care (September 1996), Vol. 19,Nr. 9, 1006-1009

44. New J.P., D. McDowell, E. Burns, et al.:Problem of Amputations in Patients with NewlyDiagnosed Diabetes Mellitus, Diabetic Medicine,(1998), 15, 760-764,

45. Reike H.: Amputation der unteren Extremitätenbei Patienten mit Diabetes in Deutschland, In:M. Berger, C. Trautner, Die Forderungen von St.Vincent – Stand 1996 in Deutschland, Kirchheim-Verlag Mainz, (1996), 80-93

46. Ward J.D.: The Cost of Diabetic Foot Problems,PharmacoEconomics (1995), 8, (Suppl. 1), 55-57

47. Laing P., D. Cogley, L. Klenerman: Economicaspects of the diabetic foot, The Foot, (1991), 1,111-112

111

48. Sedory Holzer S. E., A. Camerota, L. Martens,et al.: Costs and Duration of Care for LowerExtremity Ulcers in Patients with Diabetes, ClinicalTherapeutics, (1998), Vol. 20, Nr.1, 169-181

49. Apelqvist J.: Wound Healing in Diabetes,Clinics in Podiatric Medicine and Surgery (January1998), Vol. 15, 21-39

50. Ragnarson-Tennvall G., J. Apelqvist: Cost-Effective Management of Diabetic Foot Ulcers,Pharmaconomics (July 1997), 12 (1), 42-53

51. Apelqvist J., G. Ragnarson-Tennvall, J.Larsson, et al.: Long-Term Costs for Foot Ulcers inDiabetic Patients in a Multidisciplinary Setting,Foot & Ankle International (July 1995), Vol. 16, Nr.7, 388-394

52. Ollendorf D. A., T. Cooper, J.G. Kotsanos, etal.: Potential Economic Benefits of Lower-ExtremityAmputation Prevention Strategies in Diabetes,Diabetes Care (August 1998), Vol. 21, Nr. 8,1240-1245

53. Henriksson F., B. Jönsson: Diabetes: the costof illness in Sweden, J Intern Med (December1998), 244 (6), 461-468

54. Mehta S.S., S. Suzuki, H.A. Glick, et al.:Determining an episode of care using claims data.Diabetic foot ulcer, Diabetes Care, (July 1999), 22,7, 1110-1115

55. Assal, J.-Ph.: Cost-Effectiveness of DiabetesEducation, PharmacoEconomics (1995), 8,(Suppl. 1) 68-71

56. Gockel P.: Diabetiker mit fortgeschrittenenSpätkomplikationen – Die Bedeutung des sozialenNetzes für die Lebensqualität der Betroffenen,Diplomarbeit für die Staatliche Abschlußprüfung imFachbereich Sozialwesen, Studienrichtung Sozial-arbeit an der Katholischen Fachhochschule NWPaderborn (1997)

57. Brod M.: Quality of life issues in patients withdiabetes and lower extremity ulcers: patients andcare givers, Quality of Life Research, (1998), Vol.7, 365-372

58. Phillips T., B. Stanton, A. Provan, et al: A studyof the impact of leg ulcers on quality of life:Financial, social, and psychologic implications,J Am Acad Dermatol (1994), 31, 49-53

59. Carrington A.L., S.K.V. Mawdsley, M. Morley, etal.: Psychological status of diabetic people withor without lower limb disability, Diabetes Researchand Clinical Practice (1996), 32, 19-25

60. Foster A.: Psychological aspects of treatingthe diabetic foot, Practical Diabetes International(March/April 1997), Vol. 14, Nr. 2, 56-58

61. Armstrong D.G., L.A. Lavery, L.B. Harkless:Who is at risk for diabetic foot ulceration?, Clinicsin Podiatric Medicine and Surgery (January 1998),Vol. 15, Nr. 1, 11-17

62. Lavery L.A., E.J.G. Peters, D.G.A. Armstrong:Pathways to Diabetic Foot Ulceration, Diabetes,(May 1998), 47, Suppl.1, A 19

63. Pham H., C. Harvey, B.I. Rosenblum, et al.:Risk Factors for the Development of FootUlceration: One Year Prospective Follow-Up, Dia-betes, (May 1998), 47, Suppl.1, A 19

64. Fernando D.J.S., E. A. Masson, A. Veves, etal.: Relationship of Limited Joint Mobility to Abnor-mal Foot Pressures and Diabetic Foot Ulceration,Diabetes Care (January 1991), Vol. 14, Nr. 1, 8-11

65. Masson E.A., E.M. Hay, I. Stockley, et al.: Ab-normal Foot Pressures Alone May not CauseUlceration, Diabetic Medicine, (1989), 6, 426-428

66. Brink T.: Induration of the Diabetic Foot Pad:Another Risk Factor for Recurrent NeuropathicPlantar Ulcers, Biomedizinische Technik, (1995),Vol.40, Nr. 7-8, 205-209

67. Brash P.D., J. Foster, W. Vennar, et al.:Magnetic resonance imaging techniquesdemonstrate soft tissue damage in the diabeticfoot, Diabetic Medicine (1999), 16, 55-61

68. Young M.J., P.R. Cavanagh, G. Thomas, et al.:The Effect of Callus Removal on Dynamic PlantarFoot Pressures in Diabetic Patients, DiabeticMedicine, (1992), 9, 55-57

69. Pham H., L.A. Lavery, C. Harvey, et al.: Riskfactors of foot ulceration in a large diabeticpopulation: two year prospective follow-up,Diabetologia, (August 1998), Vol. 41, Suppl. 1, A73

70. Day M.R., L. B. Harkless: Factors AssociatedWith Pedal Ulceration in Patients With DiabetesMellitus, J Am Podiatr Med Assoc, (August 1997),Vol. 87, Nr. 8, 365-369

71. Reiber G. E., D.G. Smith, L. Vileikyte, et al.:Causal Pathways for Incident Lower-ExtremityUlcers in Patients With Diabetes From TwoSettings, Diabetes Care, (January 1999), Vol. 22,Nr. 1, 157-162

112

72. Peter-Riesch B., J.-Ph. Assal, G. Reiber: PivotalEvents: a neglected field of factors leading tomajor diabetic foot complications, Diabetologia,(August 1996), Vol.39, Suppl.1, A 265

73. Eneroth M., J. Apelqvist, A. Stenström: ClinicalCharacteristics and Outcome in 223 DiabeticPatients with Deep Foot Infections, Foot & AnkleInternational, (November 1997), Vol. 18, Nr. 11,716-722

74. Larsson J., C.-D. Agardh, J. Apelqvist, et al.:Local signs and symptoms in relation to finalamputation level in diabetic patients, Acta OrthopScand (1994), 65 (4), 387-393

75. Crausaz F.M., C. Liniger, A. Albeanu, et al.: Ad-ditional Factors Associated with Plantar Ulcers inDiabetic Neuropathy, Diabetic Medicine (1988), 5,771-775

76. Shaw J.E., A.J.M. Boulton: Poor vision as acontributory factor in diabetic neuro-arthropathy,Diabetes Research and Clinical Practice (1997),38, 21-23

77. El-Shazly M., M. Abdel-Fattah, N. Scorpiglione,et al.: Risk Factors for Lower Limb Complicationsin Diabetic Patients, Journal of Diabetes and ItsComplications, (1998), 12, 10-17

78. Morbach S., S. Herold, H.R. Ochs, F. Macken-brock: Einfluss stadiengerechter diabetesadaptier-ter Schuhversorgung auf die Rezidivhäufigkeitschuhbedingter Fußläsionen, Diabetes und Stoff-wechsel, (1999), 8, Suppl. 1, 217

79. Rupp U., K. Zink, N. Hermanns, et al.: Zwei-Jahres-Follow-up bei Patienten mit diabetischemFußsyndrom, Diabetes und Stoffwechsel (1999),8, Suppl. 1, 76

80. Balakrishnan C., T.P. Rak, M. S. Meininger:Burns of the neuropathic foot following use oftherapeutic footbaths, Burns, (1995), Vol. 21, Nr. 8,622-623

81. Das A.K., A. Agarwal: A precipitating factor intropical diabetic foot ulcer in India, J AssocPhysicians India, (May 1991), 39 (5), 426

82. Akanji A.O.: Two unusual predisponsingfactors for diabetic pedal ulceration in Nigerians,Trop. Goegr. Med., (1990), 42, 83-86

83. Ewins D.L., K. Bakker, M.J. Young, et al.:Alternative Medicine: Potential Dangers for theDiabetic Foot, Diabetic Medicine, (1993), 10,980-982

84. G. Ragnarson Tennval: The Diabetic Foot –Costs, health economic aspects, prevention andquality of life, Doctoral dissertation, (Jan. 2001),Lund University, Sweden

85. Redeker J., G. Redeker, E. Klein, et al.: HohePrävalenz diabetesassozierter Krankheiten bei209 Patienten mit diabetischem Fußsyndrom undbei 209 „Kontrollen“, Diabetes und Stoffwechsel,(1997), 6, Suppl. 1, 135

86. Shawis TN., A. Logan, GA. Lomax, et al.:Diabetic black toe is a marker for fatal myocardialinfarction, Practical Diabetes International, (March/April 1998), Vol. 15, Nr. 2, 43-44

87. Reike H.: Einleitung und Epidemiologie, In:H. Reike, Diabetisches Fußsyndrom – Diagnostikund Therapie der Grunderkrankungen und Kompli-kationen, de Gruyter-Verlag Berlin, (1999), 1-12

88. Criqui M.H., J.O. Denenberg: The generalizednature of atherosclerosis: how peripheral arterialdisease may predict adverse events from coronaryartery disease, Vascular Medicine, (1998), 3,241-245

89. Guerrero-Romero F., M. Rodríguez-Morán:Relationship of Microalbuminuria With the DiabeticFoot Ulcers in Type II Diabetes, Journal of Dia-betes and Its Complications, (1998), 12, 193-196

90. Zander E., P. Heinke, D. Gottschling, et al.:Increased prevalence of elevated urinary albuminexcretion rate in type 2 diabetic patients sufferingfrom ischemic foot lesions, Exp Clin EndocrinolDiabetes, (1997), 105, Suppl. 2, 51-53

91. Glynn J.R., E.K. Carr, W.J. Jeffcoate:Foot ulcers in previously unrecognized diabetesmellitus, Br. Med. J., (1990), 300, 1046-1047

92. Boulton A.J.M., F.A. Gries, J.A. Jervell:Guidelines for diagnosis and outpatientmanagement of diabetic peripheral neuropathy.,Diabet Med, (June 1998), Vol.15, Nr.6, 508-514

93. Report and recommendations of the San Anto-nio conference on diabetic neuropathy: Diabetes,(July 1988), 37 (7), 1000-1004

94. Thivolet C.,J. El Farkh, A. Petiot, et al.:Measuring Vibration Sensations With GraduatedTuning Fork, Diabetes Care, (October 1990),Vol. 13, Nr. 10, 1077-1080

95. Boulton A.J.M., D. B. Kubrusly, J. H. Bowker,et al.: Impaired Vibratory Perception and DiabeticFoot Ulceration, Diabetic Medicine, (1986),Vol. 3, 335-337

113

96. Mayfield J. A., J. R. Sugarman: The use of theSemmes-Weinstein Monofilament and OtherThreshold Tests for Preventing Foot Ulceration andAmputation in Persons with Diabetes, The Journalof Family Practice, (November 2000), Vol. 49,Nr. 11, 17-29

97. Windecker R., S. Kindermann, M. Spraul:Tip Therm: a simple screening method fortemperature sensation, Diabetologia, (June 1997),Vol. 40, Suppl. 1, A 483

98. Levy D.M., D.A. Rowley, R.R. Abraham:Changes in cholinergic sweat gland activation indiabetic neuropathy identified by computerisedsweatspot analysis, Diabetologia (1991), 34,807- 812

99. Sangiorgio L., R. Iemmolo, R. Le Moli, et al.:Diabetic neuropathy: prevalence, concordancebetween clinical and electrophysiological testingand impact of risk factors, Panminerva Med.,(1997), 39, 1-5

100. Boulton A.J.M.: Peripheral neuropathyand the diabetic foot, The Foot, (1992), 2, 67-72

101. Taylor R., G.D. Stainsby, D.L. Richardson:Rupture of the plantar fascia in the diabetic footleads to toe dorsoflexion deformity, Diabetologia,(August 1998), Vol. 40, Suppl. 1, 1068-1071

102. Ryder R.E.J., R.L. Kennedy, P.G. Newrick, etal.: Autonomic Denervation may be a Prerequisiteof Diabetic Neuropathic Foot Ulceration, DiabeticMedicine, (1990), 7, 726-730

103. Jeffcoate W., J. Lima, L. Nobrega:The Charcot foot, Diabetic Medicine, (2000), 17,253-258

104. Thomson F.J., E.A. Masson, A.J.M. Boulton:The Clinical Diagnosis of Sensory Neuropathyin Elderly People, Diabetic Medicine, (1993), 10,843-846

105. Liniger C., A. Albeanu, D. Bloise, et al.:The Tuning Fork Revisited Diabetic Medicine,(1990), 7, 859-864,

106. Cavanagh P.R., J.S. Ulbrecht: Clinical plantarpressure measurement in diabetes: rationaleand methodology, The Foot, (1994), 4, 123-135

107. Armstrong D.G., W.F. Todd, L.A. Lavery, et al.:The Natural History of Acute Charcot´s Arthropathyin a Diabetic Foot Specialty Clinic, J Am PodiatrMed Assoc, (June 1997) 87(6), 272-278

108. Sella E.J., C. Barrette: Staging of CharcotNeuroarthropathy Along the Medical Column of theFoot in Diabetic Patient, Foot & Ankel Surgery,(1999), 38 (1), 34-40

109. Young, M.J., P.L. Selby, A. Marshall, et al.:Osteopenia, Neurological Dysfunction, andthe Development of Charcot Neuroarthropathy,Diabetes Care, (January 1995), Vol. 18, Nr. 1,34-38

110. Wetz H.H.: Diabetisch-neuropathischeOsteoarthropathie, Deutsches Ärzteblatt,(October 1998), Vol.95, Nr. 43, A-2701–2705

111. Jude E.B., P.L. Selby, M. Donohue, et al.:Pamidronate in diabetic Charcot neuroarthropathy:a randomised placebo controlled trial, DiabeticMedicine, (March 2000), Vol. 17, Suppl. 1, P81

112. Ebert D.: Überblick über die häufigsten klini-schen Manifestationen der peripheren arteriellenVerschlußkrankheiten im Alter, ihre Diagnostik undstadiengerechte Therapie, ZaeFQ, (1997), 91,525-531

113. Bundó M., J. Aubà, R. Vallés, et al.: PeripheralArteriopathy in type 2 Diabetes Mellitus, AtenciónPrimaria, (June 1998), Vol. 22, Nr. 1, 5-11

114. Osmundson P.J, M. O’Fallon, B.R. Zimmer-man, et al.: Course of Peripheral Occlusive ArterialDisease in Diabetes, Diabetes Care, (February1990), Vol. 13, Nr. 2 143-152

115. Tooke J. E.: European Consensus Documenton Critical Limb Ischaemia: Implications forDiabetes, Diabetic Medicine, (1990), 7, 544-546

116. Sambraus H. W.: Die hydrostatische Zehen-druckmessung, Dtsch. Med. Wschr., (1996), 121,364-368

117. Chantelau E., H.W. Sambraus: HydrostaticSystolic Toe Pressure for Diagnosis of PeripheralIschaemic Vessel Disease in Diabetes Mellitus,Eur J Vasc Endovasc Surg, (1996), 12, 125-128

118. Hiller B.: The hydrostatic measurement ofsystolic toe blood pressure: a preliminary valida-tion of the method, VASA, (1998), 27, 229-232

119. Chantelau E., K.M. Lee: Ankle/arm pressureindex in diabetes mellitus, Diabetologia, (February1994), 37(2), S. 223

120. Edmonds M. E., N. Morrison, J. W. Laws,et al.: Medial arterial calcification and diabeticneuropathy, British Medical Journal, (March1982),Vol. 284, Nr. 27, 928-930

114

121. Chantelau E., X.Y MA., S. Herrnberger, et al.:Effect of Medial Arterial Calcification on O2 Supplyto Exercising Diabetic Feet, Diabetes, (August1990), Vol. 39, 938-941

122. Chantelau E., K.M. Lee, R. Jungblut: Distalarterial occlusive disease in diabetes is related tomedial arterial calcification, Exp Clin EndocrinolDiabetes, (1997), 105, Suppl. 2, 11-13

123. Goss D.E., J.de Trafford, V.C Roberts, M.D.Flynn, et al.: Raised Ankel/Brachial Pressure Indexin Insulin-treated Diabetic Patients, DiabeticMedicine, (1989), 6, 576-578

124. Young M.J., J.E. Adams, G.F. Anderson, et al.:Medial arterial calcification in the feet of dia-betic patients and matched non-diabetic controlsubjects, Diabetologia, (1993), 36, 615-621

125. Luft D., C. Maisch, V. Dörnberger, et al.:Mönckeberg´sche Mediasklerose bei Diabetikern,Diabetes und Stoffwechsel, (1999), 8, 75-81

126. LoGerfo F.W., J.D. Coffman: Vascular andMicrovascular Disease of the Foot in Diabetes,The New England Journal of Medicine, (1984), 20,Vol. 311, Nr. 25, 1615-1619

127. Chantelau E., M. Ibeling: Gibt es eineobliterierende „diabetische Mikroangiopathie“ amdiabetischen Fuß? – Ein Vergleich klinischer undhistologischer Befundberichte, Akt. Chir., (1993),28, 249-253

128. Flynn M.D., J.E. Tooke: Aetiology of DiabeticFoot Ulceration: A Role for the Microcirculation?,Diabetic Medicine, (1992), 8, 320-329

129. Edmonds M., A. Foster, P. Baskerville, et al.:Diabetic gangrene: the role of septic vasculitisand intimal hyperplasia in the neuropathic andischaemic foot, Diabetologia, (1995), Vol. 38,Suppl. 1, A274

130. Kreitner K.-F., P. Kalden, A. Neufang, et al.:Diabetes and Peripheral Arterial OcclusiveDisease: prospective comparison of contrast-enhanced three-dimensional MR Angiography withconventional Digital Subtraction Angiography,AJR, (2000), 174, 171-179

131. Back M.R., J.G. Caridi, I.F. Hawkins, et al.:Angiography with carbon dioxide (CO2), SurgicalClinics of North America, (1998), Vol. 78, Nr. 4,575-591

132. Macfarlane R., W. Jeffcoate: How to describea foot lesion with clarity and precision, TheDiabetic Foot, (1998), Vol. 1, Nr. 4, 135-144

133. Jeffcoate W.J., R.M. Macfarlane, E.M.Fletcher: The Description and Classification ofDiabetic Foot Lesions, Diabetic Medicine, (1993),10, 676-679

134. Apelqvist J., J. Castenfors, J. Larrson, et al.:Wound Classification is More Important ThanSite of Ulceration in the Outcome of Diabetic FootUlcers, Diabetic Medicine, (1989), 6, 526-530

135. Wagner F.W.: The Dysvascular Foot: A Systemfor Diagnosis and Treatment, Foot & Ankle, (1981),Vol. 2, Nr. 2, 64-122

136. Rischbieter E., H. Reike: Stellenwert derStadieneinteilung und Klassifikation beim Diabeti-schen Fußsyndrom, Diabetes und Stoffwechsel,(1998), 7, Suppl. 1, 83-84

137. Lavery A.L., D.G. Armstrong, L.B. Harkless:Classification of Diabetic Foot Wounds, TheJournal of Foot and Ankle Surgery, (1996), Vol. 35,Nr. 6, 528-531

138. Armstrong D.G., L.A. Lavery, L.B. Harkless:Validation of a Diabetic Wound ClassificationSystem, Diabetes Care, (1998), Vol. 21, Nr. 5,855-859

139. Armstrong D.G., L.A. Lavery: Evidence-basedoptions for off-loading diabetic wounds, Clinicsin Podiatric Medicine and Surgery, (1998), Vol.15,Nr.1, 95-103

140. Fleischli J.G., L.A. Lavery, S.A. Vela, et al.:Comparison of Strategies for Reducing Pressure atthe Site of Neuropathic Ulcers, Journal of theAmerican Podiatric Medical Association, (1997),Vol. 87, Nr. 10, 466-472

141. Müller M.J., J.E. Diamond, D.R. Sinacore, etal.: Total Contact Casting in Treatment of DiabeticPlantar Ulcers, Diabetes Care, (1989), Vol. 12,Nr. 6, 384-388

142. Needleman R.L.: Successes and Pitfalls inthe Healing of Neuropathic Forefoot Ulcerationswith the IPOS Postoperative Shoe, Foot & AnkleInternational, (1997), Vol. 18, Nr. 7, 412-417

143. Chantelau E., U. Breuer, A.C. Leisch, et al.:Outpatient Treatment of Unilateral DiabeticFoot Ulcers with “Half Shoes”, Diabetic Medicine,(1993), 10, 267-270

144. Reike, H.: Wundheilung und lokale Wund-behandlung beim diabetischen Fuß-Syndrom, In:E. Chantelau, Amputation? Nein Danke!,Kirchheim-Verlag, Mainz, 1. Auflage (1995),177-202

115

145. Gough A., M. Clapperton, N. Rolando, et al.:Randomised placebo-controlled trial of granulo-cyte-colony stimulating factor in diabetic footinfection, The Lancet, (1997), Vol. 350, 855-859

146. Hehenberger K., A. Hansson: High Glucose-Induced Growth Factor Resistance in HumanFibroblasts Can be Reversed by Antioxidants andProtein Kinase C-Inhibitors, Cell Biochemistryand Function, (1997), Vol.15, 197-201

147. Loots M.A.M., E.N. Lamme, J.R. Mekkes,et al.: Cultured fibroblasts from chronic diabeticwounds on the lower extremity (non-insulin-dependent diabetes mellitus) show disturbedproliferation, Arch Dermatol Res, (1999), 291,93-99

148. Hehenberger K., J.D. Heilborn, K. Brismar,A. Hansson: Inhibited proliferation of fibroblastsderived from chronic diabetic wounds and normaldermal fibroblasts treated with high glucose isassociated with increased formation of L-lactate,Wound Repair Regen, (1998), 6 (2),135-141

149. Lawrence I.G., J.T. Lear, A.C. Burden:Alginate dressings and the diabetic foot ulcer,Practical Diabetes International, (March/April1997), Vol. 14, Nr. 2, 61-64

150. Lithner F.: Adverse effects on diabeticulcers of highly adhesive hydrocolloid occlusivedressing, Diabetes Care, (July 1990), Vol. 13,Nr. 7, 814-815

151. Apelqvist J., G. Ragnarson-Tennvall,J. Larsson: Topical Treatment of Diabetic FootUlcers: an Economic Analysis of TreatmentAlternatives and Strategies, Diabetic Medicine,(1995), 12, 123-128

152. Fisken R.A., M. Digby: Which dressing fordiabetic foot ulcers?, Practical Diabetes Inter-national, (July/August1996), Vol. 13, Nr.4, 107-109

153. Foster A.V.M., S. Spencer, M.E. Edmonds:Deterioration of diabetic foot lesions underhydrocolloid dressings, Practical Diabetes Interna-tional, (March/April 1997), Vol. 14, Nr. 2, 62-64

154. Jones V., D. Gill: Hydrocolloid dressings anddiabetic foot lesions, The Diabetic Foot, (1998),Vol. 1, Nr. 4, 127-134

155. Eich D., R. Stadler: Differenzierte Lokal-therapie chronischer Wunden mit modernenWundauflagen, VASA, (1999), 28, 3-9

156. Chantelau E., T. Tanudjaja, F. Altenhöfer,et al.: Antibiotic Treatment for UncomplicatedNeuropathic Forefoot Ulcers in Diabetes: aControlled Trial, Diabetic Medicine, (1996), 13,156-159

157. Foster A.V.M., M. Bates, M. Doxford, et al.:Should oral antibiotics be given to “clean” footulcers with no cellulitis?, The Diabetic Foot, ThirdInternational Symposium, 5th–8th May 1999,Nordwijkerhout, The Netherlands, o13

158. Day M.R., D.G. Armstrong: FactorsAssociated with Methicillin Resistance in DiabeticFoot Infections, The Journal of Foot & AnkleSurgery, (1997), Vol. 36, Nr. 4, 322-325

159. Tentolouris N., E. B. Jude, I. Smirnof, et al.:Methicillin-resistant Staphylococcus aureus:an increasing problem in a diabetic foot clinic,Diabetic Medicine, (1999), 16, 767-771

160. Lipsky B. A., R. E. Pecoraro, S. A. Larson,et al.: Outpatient Management of UncomplicatedLower-Extremity Infections in Diabetic Patients,Arch Intern Med, (April 1990), Vol. 150, 790-797

161. Lipsky B. A.: Osteomyelitis of the Foot inDiabetic Patients, Clincal Infectious Diseases,(1997), 25, 1318-1326

162. Venkatesan P., S. Lawn, R.M. Macfarlane,et al.: Conservative Management of Osteomyelitisin the Feet of Diabetic Patients, Diabetic Medicine,(1997), 14, 487-490

163. Lipsky B. A.: Evidence-based antibiotictherapy of diabetic foot infections, FEMSImmunology and Medical Microbiology, (1999),26, 267-276

164. Ha Van G., S. Hubert, J.-P. Danan, et al.:Treatment of Osteomyelitis in the Diabetic Foot,Diabetes Care, (1996), Vol. 19, Nr. 11, 1257-1260

165. Grayson M. L., G. W. Gibbons, K. Balogh,et al.: Probing to Bone in Infected Pedal Ulcers,JAMA, (1995), Vol. 273, Nr. 9, 721-723

166. Armstrong D. G., L. A. Lavery, M. Sariaya,et al.: Leukocytosis is a Poor Indicator of AcuteOsteomyelitis of the Foot in Diabetes Mellitus,The Journal of Foot and Ankle Surgery, (1996),Vol. 35, Nr. 4, 280-283

167. Edelson G. W., D. G. Armstrong, L. A. Lavery,et al.: The Acutely Infected Diabetic Foot Is NotAdequately Evaluated in an Inpatient Setting, ArchIntern Med, (1996), 156, 2373-2378

116

168. Brunner U., H. Zollinger: Der diabetische Fußaus der Sicht des Chirurgen, In: W. Hepp, Derdiabetische Fuß, Blackwell Wissenschafts-Verlag,Berlin-Wien, 1. Auflage (1996), 16-21

169. Bergqvist D., J. Apelqvist, G. Jörneskog,et al.: Clinical assessment of critical ischemiais always to be done prior to amputation (Article inSwedish), Läkartidningen, (1999), Vol. 96,Nr. 7, 727- 729

170. The ICAI Study Group: Prostanoids forChronic Critical Leg Ischemia, Ann Intern Med.,(1999), 130, 412-421

171. Vannini P., A. Ciavarella, A. Mustacchio, et al.:Intra-Arterial Urokinase Infusion in DiabeticPatients With Rapidly Progressive Ischemic footlesions, Diabetes Care, (1991), Vol. 14, Nr. 10,925- 927

172. Edmonds M.E., H. Walters: Angioplastyand the diabetic foot, Vascular Medicine Review,(1995), 6, 205-214

173. Jeans W. D., S.E.A Cole, M. Horrocks, et al.:Angioplasty gives good results in critical lowerlimb ischaemia. A 5-year follow-up in patients wihknown ankle pressure and diabetic status havingfemoropopliteal dilatations, The British Journalof Radiology, (1994), 67, 123-128

174. Hülsewiesche C.: Perkutane transluminaleAngioplastie zur Behandlung der arteriellen Verschlußkrankheit bei Diabetikern, Z. Herz-, Thorax-,Gefäßchir., (1997), 11, 209-213

175. Wack C., K. D. Wölfle, H. Loeprecht, et al.:Perkutane Ballondilatation bei isolierten Läsionender Unterschenkelarterien mit kritischer Bein-ischämie, VASA, (1994), 23, 1, 30-34

176. LoGerfo F.W., G.W. Gibbons, F.B. Pomposelli,et al.: Trends in the Care of the Diabetic Foot -Expanded role of Arterial Reconstruction, ArchSurg, (1992), Vol. 127, 617-621

177. Pedersen A. E., B. Bornefeldt Olsen,M. Krasnik, et al.: Halving the Number of LegAmputations: The Influence of InfrapoplitealBypass, Eur J Vacs Surg, (1994), 8, 26-30

178. Kniemeyer H. W., K.-H. Meier, E. Chantelau,et al.: Diabetes und periphere arterielle Verschluß-krankheiten - eine gefäßchirurgische Herausforde-rung, Diabetes und Stoffwechsel, (1994), 3,327-330

179. Pomposelli F. B., S. J. Jepsen, G. W. Gibbons,et al.: Efficacy of the dorsal pedal bypass for limbsalvage in diabetic patients: Short-term observa-tions, Journal of Vascular Surgery, (1990), Vol. 11,Nr. 6, 745 - 751

180. Armstrong D. G., L. A. Lavery: PlantarPressure are Higher in Diabetic Patients FollowingPartial Foot Amputation, Ostomy/Wound Manage-ment, (1998), 44 (3), 30-39

181. Murdoch D. P., D. G. Armstrong, J. B. Dacus,et al.: The Natural History of Great Toe Amputa-tions, The Journal of Foot & Ankle Surgery, (1997),36 (3), 204-208

182. Radermacher T.: Septische Knochenchirurgieam neuropathischen diabetischen Vorfuß – Nutzenund Risiken, Akt. Chir., (1997), 32, 101-103

183. Griffiths G. D., T. J. Wieman: Metatarsal HeadResection for Diabetic Foot Ulcers, Arch Surg,(1990), Vol.125, 832-835

184. Patel V. G., T. J. Wieman: Effect of MetatarsalHead Resection for Diabetic Foot Ulcers on theDynamic Plantar Pressure Distribution, The Ameri-can Journal of Surgery, (1994), Vol. 167, 297-301

185. Klein M., P.-J. Höfges, H. Kniemeyer, et al.:Transmetatarsale Grenzzonenamputation bei arte-rieller Durchblutungsstörung, Dtsch. med. Wschr.,(1990), 115, 683-688

186. Santi M. D., B. J. Thoma, R. B. Chambers:Survivorship of Healed Partial Foot Amputations inDysvascular Patients, Clinical Orthopaedics andrelated research, (1993), 292, 245-249

187. Raunest J.: Diabetisches Fußsyndrom – chir-urgische Versorgung, In: E. Chantelau, M.Spraul,Amputation? Nein Danke!, Verlag Neuer MerkurGmbH, München, 2.aktualisierte Auflage (1999),219-228

188. Laughlin R. T., R. B. Chambers: Syme Ampu-tation in Patients with Severe Diabetes Mellitus,Foot & Ankle, (1993), Vol 14, Nr. 2, 65-70

189. Moore TJ., J. Barron, F. Hutchinson, et al.:Prosthetic usage following major lower extremityamputation, Clin Orthop, (1989), 238, 219-224

190. Van Ross E.R.E.: After Amputation – Rehabili-tation of the Diabetic Amputee, J Am Podiatr MedAssoc, (1997), Vol. 87, Nr. 7, 332-335

117

191. Masson E. A., M. A. C. Cooper, A. J. M.Boulton: Split-skin Grafting in the Management ofExtensive Neuropathic Ulceration, DiabeticMedicine, (1989), 6, 171-172

192. Faglia E., G. Oriani, F. Favales, et al.:Adjunctive Systemic Hyperbaric Oxygen Therapyin Treatment of Severe Prevalently IschemicDiabetic Foot Ulcer – a randomized study, Diabe-tes Care, (1996), Vol.19, Nr. 12,1338-1343

193. Leach R. M., P. J. Rees, P. Wilmshurst:ABC of oxygen Hyperbaric oxygen therapy, BMJ,(1998), Vol. 317, 1140-1143

194. Leslie C. A., F. L. Sapico, V. J. Ginunas, et al.:Randomized Controlled Trial of Topical Hyper-baric Oxygen for Treatment of Diabetic FootUlcers, Diabetes Care, (1988), Vol. 11, Nr. 2,111-115

195. Trajanoski Z., G. A. Brunner, R. J. Gfrerer, etal.: Hyperbaric Oxygen Therapy for DiabeticFoot Ulcers, Diabetes Care, (1997), Vol. 20, Nr. 7,1207-1208

196. European Comitee on Hyperbaric Medicine:Hyperbaric oxygen in the management of footlesions in diabetic patients, Diab. Nutr. Metab.,(1999), 12, 47-48

197. Gough A., M. Clapperton, N. Ronaldo, et al.:Granulocyte-colony-stimulating factor in diabeticfoot infection, Lancet, (1997), 35, 855-859

198. Richard J.-L., J. Bringer, C. Parer-Richard, etal.: Effect of Topical Basic Fibroblast GrowthFactor on the Healing of Chronic Diabetic Neuro-pathis Ulcer of the Foot, Diabetes Care, (1995),Vol. 18, Nr. 1, 64-69

199. Wieman T. J., J. M. Smiell, Y. Su: Efficacy andSafety of a Topical Gel Formulation of Recombi-nant Human Platelet-Derived Growth Factor-BB(Becaplermin) in Patients With Chronic Neuro-pathic Diabetic Ulcers, Diabetes Care, (1998),Vol. 21, Nr. 5, 822-827

200. Edmonds M. E., A.V. Foster, M. McColgan:„Dermagraft“: a New Treatment for Diabetic FootUlcers, Diabetic Medicine, (1997), 14, 1010-1011

201. Thomas S, A. Andrews, M. Jones, et al.:Maggots are useful in treating infected or necroticwounds, BMJ, (1999), Vol. 318, 807-808

202. Mumcuoglu K. Y., A. Ingber, L. Gilead, et al.:Maggot therapy for the treatment of diabeticfoot ulcers, Diabetes Care, (1998), Vol. 21, Nr. 11,2030-2031

203. Greitemann B., R. Baumgartner: Erfahrungenmit der Anwendung von vitalen Blutegeln in derAmputationschirurgie, Med. Orth. Tech., (1996),116, 60-64

204. Clavel S.: Die Organisation einer Fußsprech-stunde in der Diabetologie, Med. Orth. Tech.,(1990), 110, 166-167

205. Miller L.V., J. Goldstein: More efficient careof diabetic patients in a country-hospital setting,New Engl J Med (1972), 286:1388-1391

206. Edmonds M.E., K. Van Acker, A.V.M. Foster:Education and the Diabetic Foot, DiabeticMedicine, (1996), 13, S61-S64

207. Malone J. M., M. Snyder, G. Anderson, et al.:Prevention of Amputation by Diabetic Education,The American Journal of Surgery, (1989), Vol. 158,520-523

208. Kruger S., D. Guthrie: Foot Care: KnowledgeRetention and Self-care Practices, The DiabetesEducator, (1992), Vol. 18, Nr. 6, 487-490

209. Barth R., L.V. Campbell, S. Allen, et al.: Inten-sive Education Improves Knowledge, Compliance,and Foot Problems in Type 2 Diabetes, DiabeticMedicine, (1991), 8, 111-117

210. Boulton A.J.M.: Why bother educatingthe multi-disciplinary team and the patient – theexample of prevention of lower extremityamputation in diabetes, Patient Education andCounseling, (1995), 26, 183-188

211. Masson E. A., S. Angle, P. Roseman, et al.:Diabetic foot ulcers - do patients know how toprotect themselves?, Practical Diabetes, (January/February 1989), Vol. 6, Nr. 1, 22-23

212. Del Aguila M. A., G. E. Reiber, T. D. Koepsell:How does Provider and Patient Awareness ofHigh-Risk Status for Lower-Extremity AmputationInfluence Foot-Care Practice?, Diabetes Care,(1994), Vol.17, Nr. 9,1050-1054

213. Fletcher E., R. MacFarlane, W. Jeffcoate, etal.: Can foot ulcers be prevented by education?,Diabetic Medicine, (1992), 9, Suppl.2, 41

214. C. Payne: Regional variations of diabetic footcomplications and podiatric services, AJPM(1999), 33 (2), 51-54

215. Spraul M., A. M. Schönbach, I. Mühlhauser,et al.: Amputationen und Mortalität bei älteren, in-sulinpflichtigen Patienten mit Typ-2-Diabetes,Zentralblatt für Chirurgie, (1999), 124, 501-507

118

216. Marciniak M.: Qualifizierte Fußpflege/Behand-lung zur Rehabilitation von Patienten mit diabeti-schem Fuß-Syndrom. Eine Kohortenstudie, Diabe-tes und Stoffwechsel, (1998), 7, 81-85

217. Ponci J.: Die Bedeutung der Fußpflege in derBehandlung des Diabetesfußes, Med. Orth. Tech.,(1990), 110, 174-175

218. Haeger J. E.: Konservative Behandlung deseingewachsenen Nagels (unguis incarnatus) beiPatienten mit diabetischer Polyneuropathie, Diabe-tes und Stoffwechsel, (1997), 6, 145-150

219. Thomson F. J., E. A. Masson: Can ElderlyDiabetic Patients Co-operate with Routine FootCare?, Age und Ageing, (1992), 21, 333-337

220. Chantelau E., A. Leisch: Footwear: Uses andAbuses, In: A.J.M. Boulton, H.Connor, P.R.Cavanagh, The Foot in Diabetes, John Wiley &Sons, Chichester, 2nd edition, (1994), 99-108

221. Edmonds M. E., M. P. Blundell, M. E. Morris,et al.: Improved Survival of the Diabetic Foot:The Role of a Specialised Foot Clinic, QuarterlyJournal of Medicine, (1986), Nr. 232, 763 - 771

222. Chantelau E., P. Haage: An Audit ofCushioned Diabetic Footwear: Relation to PatientCompliance, Diabetic Medicine, (1994), 11,114 - 116

223. Uccioli L., A. Aldeghi, E. Faglia, et al.:Manufactured Shoes in the Prevention of DiabeticFoot Ulcers, Diabetes Care, (1995), Vol. 18,Nr. 10, 1376 -1378

224. Striesow F.: Konfektionierte Spezialschuhezur Ulkusrezidivprophylaxe beim diabetischenFußsyndrom, Med Klin, (1998), 93, 695-700

225. Reike H., A. Brüning, E. Rischbieter, et al.:Rezidive von Fußläsionen bei Patienten mitdem Syndrom des diabetischen Fußes: Einfluß vonorthopädischen Maßschuhen, Diabetes undStoffwechsel, (1997), 6, 107-113

226. Presch M.: Protektives Schuhwerk beimneuropathischen diabetischen Fuß mit niedrigemund hohem Verletzungsrisiko, Med. Orth. Tech.,(1999), 119, 62-66

227. Kästenbauer T., G. Sokol, M. Auinger, et al.:Running Shoes for Relief of Plantar Pressure inDiabetic Patients, Diabetic Medincine, (1998), 15,518-522

228. Haage P.: Vorfuß-Plantardruck am dia-betischen Fuß in unterschiedlichem Schuhwerk,Med. Orth. Tech., (1994), 114, 17-21

229. Murray H. J., A. Veves, M. J. Young, et al.:Role of Experimental Socks in the Care of theHigh-Risk Diabetic Foot, Diabetes Care, (1993),Vol. 16, Nr. 8, 1190-1192

230. Veves A., E. A. Masson, D. J. S. Fernando,et al.: Use of Experimental Padded Hosiery toReduce Abnormal Foot Pressures in DiabeticNeuropathy, Diabetes Care, (1989), Vol. 12, Nr. 9,653-655

231. Soulier S.M.: The Use of Running Shoes inthe Prevention of Plantar Diabetic Ulcers, Journalof the American Podiatric Medical Association,(1986), Vol. 76, Nr. 7, 395-400

232. Perry J. E., J. S. Ulbrecht, J. A. Derr, et al.:The Use of Running Shoes to Reduce PlantarPressures in Patients Who Have Diabetes,The Journal of Bone and Joint Surgery, (1995),Vol. 77-A, Nr. 12, 1819-1828

233. Knowles E.A., A.J.M. Boulton: Do PeopleWith Diabetes Wear Their Prescribed Footwear?,Diabetic Medicine, (1996), 13, 1064-1068

234. Chantelau E., V. Jung: Qualitätskontrolle undQualitätssicherung bei der Schuhversorgungdes diabetischen Fußes, Rehabilitation, (1994), 33,35-38

235. Breuer U.: Diabetic patient´s compliancewith bespoke footwear after healing of neuropathicFoot ulcers, Diabete & Metabolisme, (1994), 20,415-419

236. Wooldridge J., J. Bergeron, C. Thornton:Preventing Diabetic Foot Disease: Lessons fromthe Medicare Therapeutic Shoe Demonstration,American Journal of Public Health, (July 1996),Vol. 86, Nr. 7, 935-938

237. Zink K., C. Beier, J. Stumpf, et al.: Bedeutungder Tragezeit eines Diabetesschutzschuhes (DSS)für die Prävention des diabetischen Fußsyndroms(DFS), Diabetes und Stoffwechsel, (1998), 7,Suppl. 1, 140

238. Litzelman D. K., D. J. Marriott, F. Vinicor: TheRole of Footwear in the Prevention of Foot Lesionsin Patients With NIDDM - Conventional wisdom orevidence-based practice?, Diabetes Care, (1997),Vol. 20, Nr. 2, 156-162

119

239. Chantelau E., A. Gede: Diabetische Füßesind breiter als normales Schuhwerk, Diabetes undStoffwechsel, (1999), 8, Suppl. 1, 16

240. Hlaváãek P., P. Stastná: Analyses of Dimen-sional changes in the feet of type II diabetics,The Diabetic Foot, Third International Symposium,5th–8th May 1999, Nordwijkerhout, The Nether-lands, O 32

241. Ebskov B.: The Danish Amputation Register1972-1984, Prosthetics and Orthotics International,(1986), 10, 40-42

242. Paetow P.: Operative und konservative Thera-pie des „diabetischen Fußes“ in einem Kranken-haus der Grundversorgung, Präv Rehab, (1991),Vol. 3, Nr. 3, 112 -118

243. Jung V.: Fuß-Erhalt bei diabetischer Gangrän,Zentralblatt für Chirurgie, (1996), 121, 387-393

244. Macfarlane R.M., W.J. Jeffcoate: Diabetic footulcers: comparison of outcome between 1984 and1994, Diabetic Medicine (1996), Vol.13, Suppl.3,PS55

245. Holstein P., N. Ellitsgaard, B. BornefeldtOlsen, et al.: Decreasing incidence of majoramputations in people with diabetes, Diabetologia,(2000), 43, 844-847

246. Larsson J., J. Apelqvist, C.-D. Agardh,et al.: Decreasing incidence of major amputationsin Diabetic Patients: a Consequence of aMultidisciplinary Foot Care Team Approach?,Diabetic Medicine, (1995), 12, 770-776

247. Faglia E., F. Favales, A. Aldeghi, et al.:Change in Major Amputation Rate in a CenterDedicated to Diabetic Foot Care During the 1980s:Prognostic Determinants for Major Amputation,Journal of Diabetes and Ist Complications, (1998),12, 96-102

248. Reike H., A. Wagner, Th. Rath, et al.:Reduction of major amputations in patients withdiabetic foot syndrome: experience of specialisedfoot care unit, Diabetic Foot Study Group of theEASD, September 14th–16th 2000, Fiuggy (Italy),

249. Holstein P. E., S. Sørensen: Limb SalvageExperience in a Multidisciplinary Diabetic FootUnit, Diabetes Care, (1999), Vol. 22, Suppl. 2,B97–B103

250. Morbach S., J. Möllenberg, C. Quante,H. R. Ochs: Specialised Care of the Diabetic Foot– Four-Year-Experience from an outpatient DiabeticFoot Clinic, Foot – The Congress, EFAS European

Foot and Ankle Societies, June 4th–6th 1998,Cologne (Germany)

251. Armstrong D. A., L. B. Harkless: Outcomes ofPreventative Care in a Diabetic Foot SpecialtyClinic, The Journal of Foot & Ankle Surgery, (1998),Vol. 37, Nr. 6, 460-466

252. Brunner G., S. Schattenberg, T. Pieber:Therapie und Prophylaxe des diabetischen Fuß-syndroms in einer Diabetesambulanz, Diabetesund Stoffwechsel, (1994), 3, 309

253. Partl M.: Nachsorge von Patienten mit diabeti-schem Fuß durch Hausärzte oder Spezial-ambulanz - Auswirkungen auf die Amputations-rate, Gesundh.-Wes., (1994), 56, 215-219

254. Morbach S., H. R. Ochs: Auswirkungen derBetreuung durch eine Spezialambulanz aufden Verlauf von Rezidivläsionen bei Patienten mitdiabetischem Fußsyndrom (DFS), Diabetesund Stoffwechsel, (1997), 6, Suppl. 1, 133-134

255. Jaegeblad G., J. Apelqvist, P.Nyberg, et al.:The diabetic foot: from ulcer to multidisciplinaryteam approach a process analysis, The DiabeticFoot, Third International Symposium, 5th– 8th May1999, Nordwijkerhout, The Netherlands, p87

256. Morbach S., H. Furchert, J. Möllenberg, C.et al.: Bedeutung zielgerichteter Informationvon Risikopatienten für Präsentation und Verlauf,CF Journal (2001); 5, Nr.1, 38-42

257. Veves A., L. Uccioli, C. Manes, et al.:Comparison of Risk Factors for Foot Problems inDiabetic Patients Attending Teaching Hospital Out-patient Clinics in Four Different European States,Diabetic Medicine, (1994), 11, 709-711

258. Frykberg R.G., A. Piaggesi, V.M. Donaghue,et al.: Difference in treatment of foot ulcerations inBoston, USA and Pisa, Italy, Diabetes Researchand Clinical Practice, (1997), 35, 21-26

259. Tovey F.: The diabetic foot, Tropical Doctor,(1997), 27, Nr.4, 194-195

260. Bosseri S., G. Gill: Hand and foot sepsis inLibyan diabetic patients, Tropical Doctor, (1997),27, Nr.4, 232-233

261. Akanji A. O., O. O. Famuyiwa, A. Adetuyibi:Factors Influencing the Outcome of Treatmentof Foot Lesions in Nigerian Patients with DiabetesMellitus, Quarterly Journal of Medicine, (1989),Nr. 271, New Series 73, 1005-1014

120

262. Morbach S., J. Möllenberg, H. R. Ochs, et al.:Regional Variation of Risk Factors and ClinicalPresentation of Diabetic Foot lesions, Diabetologia,(2000), 43, Suppl. 1, A244

263. Viswanathan V., C. Snehalatha,A. Ramachandran: Socio-Cultural Practices thatMay Affect the Development of the Diabetic Foot,IDF Bulletin, (1997), Vol. 42, Nr. 4, 10-12

264. Shridhar G.R.: Rat bites and diabeticfoot ulcer, JAPI, (1992), Vol. 40, Nr. 4, 281-282

265. Ebskov B., L. Ebskov: Major lower limbamputation in diabetic patients: developmentduring 1982 to 1993, Diabetologia, (1996),39, 1607-1610

266. Spraul M.: Prävention des diabetischenFußsyndroms, Der Internist, (1999), 40,1056-1066

267. Apelqvist J., D. Bergqvist, M. Eneroth, et al.:The diabetic foot. Optimal prevention andtreatment can half the risk of amputation. (Article inSwedish), Läkartidningen, (1999), 96 (1-2),37-41

DE – PAUL HARTMANN AG89522 Heidenheim

AT – PAUL HARTMANN Ges.m.b.H.2355 Wiener Neudorf

CH – IVF HARTMANN AG8212 Neuhausen

The HARTMANN medical edition series of publications deals with current subjects from the areas of medicine and nursing. They em-phasise not only basic knowledge, but also present specialist and interdisciplinary developments. The information goes beyond the products and is particularly important.

At a time of rapidly evolving scien-tific knowledge, information must above all be up to date. With this in mind, this series of books aims to be a source of advice not only for experienced workers. Those who are approaching new areas of medicine and nursing for the first time are shown modern treatment methods and are given useful tips.

ISBN 3-929870-34-7 B 57

VAE

(040

4) 0

87 4

51/3