DIABETES CASE DIABETES CASE PRESENTATIONSPRESENTATIONS

33rdrd – Chronic complications – Chronic complications

1. Diabetic retinopathy1. Diabetic retinopathy

Early subclinical abnormalities of Early subclinical abnormalities of

the retinal vessels:the retinal vessels: thickening of the basement membranethickening of the basement membrane loss of pericytes (the contractile cells loss of pericytes (the contractile cells

that control vessel calibre and flow)that control vessel calibre and flow) increased blood flowincreased blood flow increased capillary permeability increased capillary permeability

(leakage)(leakage)

Simplified grading of diabetic Simplified grading of diabetic retinopathyretinopathy

Background (Level 1)Background (Level 1) MicroaneurysmsMicroaneurysms Retinal haemorrhages Retinal haemorrhages any exudates (hard exudates) any exudates (hard exudates)

Preproliferative (Level 2)Preproliferative (Level 2) Venous beadingVenous beading Venous loop or reduplicationVenous loop or reduplication Intraretinal microvascular abnormalities (IRMA)Intraretinal microvascular abnormalities (IRMA) Multiple deep, round haemorrhagesMultiple deep, round haemorrhages Cotton-wool spotsCotton-wool spots

Proliferative (Level 3)Proliferative (Level 3) New vessels on disc (NVD)New vessels on disc (NVD) New vessels elsewhere (NVE)New vessels elsewhere (NVE) Preretinal or vitreous hemorrhagePreretinal or vitreous hemorrhage Preretinal fibrosis Preretinal fibrosis tractional retinal detatchment tractional retinal detatchment

MaculopathyMaculopathy Exudate within a disc area (DA) of foveaExudate within a disc area (DA) of fovea Retinal thickening within DA of foveaRetinal thickening within DA of fovea Microaneurysm or hemorrhage within DA of foveaMicroaneurysm or hemorrhage within DA of fovea

Screening for diabetic Screening for diabetic retinopathyretinopathy

Regular examination of the eye in the diabetic Regular examination of the eye in the diabetic patient is essentialpatient is essential visual acuity measurementvisual acuity measurement examination of the fundus through dilated pupilsexamination of the fundus through dilated pupils digital fundus photographydigital fundus photography

yearly examinations for those with no yearly examinations for those with no retinopathyretinopathy from puberty / 5 yrs after diagnosis for T1DMfrom puberty / 5 yrs after diagnosis for T1DM from diagnosis for T2DMfrom diagnosis for T2DM

6-monthly for those with background 6-monthly for those with background retinopathyretinopathy

Treatment for DRTreatment for DR

Strict glycaemic controlStrict glycaemic control Strict blood pressure controlStrict blood pressure control ACE inhibitorsACE inhibitors Early detectionEarly detection Prompt treatmentPrompt treatment

Panretinal photocoagulation Panretinal photocoagulation EducationEducation

2. Diabetic nephropathy2. Diabetic nephropathy

Pathological changes: glomerulus + tubular interstitiumPathological changes: glomerulus + tubular interstitium

Glomerulus:Glomerulus: at diagnosis of DM - enlarged because of the increased capillary at diagnosis of DM - enlarged because of the increased capillary

surface areasurface area

subsequently, glomerular enlargement is caused by basement subsequently, glomerular enlargement is caused by basement

membrane thickening and (usually) expansion of the mesangiummembrane thickening and (usually) expansion of the mesangium

Tubular interstitium:Tubular interstitium: ttotal kidney volume is also increased, mainly through expansion of otal kidney volume is also increased, mainly through expansion of

tubular tissuetubular tissue

basement membrane thickeningbasement membrane thickening

atrophyatrophy

interstitial fibrosisinterstitial fibrosis

arteriosclerosisarteriosclerosis

Glomerular filtration rate (GFR):Glomerular filtration rate (GFR): early in diabetes – increased because of early in diabetes – increased because of

the increased filtration areathe increased filtration area later declines in parallel with mesangial later declines in parallel with mesangial

expansion and the resultant glomerular expansion and the resultant glomerular occlusionocclusion

The natural history of diabetic The natural history of diabetic nephropathy is marked by increasing nephropathy is marked by increasing loss of protein (mostly albumin) in the loss of protein (mostly albumin) in the urineurine

Urinary albumin Urinary albumin excretionexcretion

AERAER 24-h urine 24-h urine collectioncollection

Overnight urine Overnight urine collectioncollection (10 (10--1212hh))

albumin:creatininalbumin:creatinine ratioe ratio

NormoalbuminuriNormoalbuminuria a < 30 mg/24 h< 30 mg/24 h < 20 μg/min < 20 μg/min < 30 mg/g < 30 mg/g

MicroalbuminuriaMicroalbuminuria 30-300 mg/24 h30-300 mg/24 h 20-200 20-200 μg/min μg/min 30-300 mg/g 30-300 mg/g

ProteinuriaProteinuria > 300 mg/24 h> 300 mg/24 h > 200 μg/min > 200 μg/min > 300 mg/g > 300 mg/g

AER = albumin excretion ratealbumin excretion rate

The stages and The stages and determinants of DNdeterminants of DN

Normoalbuminuria

Microalbuminuria

Intermitent proteinuria

Proteinuria End-stage renal disease

Sustained normoalbuminuria

Sustained microalbuminuria

Diabetes durationBaseline AERGlycaemic controlGenetic susceptibilityEthnic minorities

BPGlycaemic control

BP

50 %

50 %

50 %

30 %

20 %

Mogensen classification (1)Mogensen classification (1)

SStatagege I (rena I (renal l hhyyperfuncperfunction / tion / hhyypertropertrophyphy))

from diagnosis of DMfrom diagnosis of DM good glycemic controlgood glycemic control → reversib → reversiblele GFRGFR byby 20-50 % ( 20-50 % (>150 ml/min/1,73 m2)>150 ml/min/1,73 m2) posposssibiblele microalbuminuri microalbuminuriaa (tran (transitorysitory!)!) size of kidneyssize of kidneys ( (ultrasonographyultrasonography) ) and of and of

glomerglomerulesules ( (biopsybiopsy)) Electronic microscope: normal basal membraneElectronic microscope: normal basal membrane normal BPnormal BP

Mogensen classification (2)Mogensen classification (2)

StaStagege II – II – asymptomaticasymptomatic, , normoalbuminurinormoalbuminuriaa

first 5 yrs from diagnosis of DMfirst 5 yrs from diagnosis of DM 5-7 5-7 yrs from onset of diseaseyrs from onset of disease: 30-50 % → sta: 30-50 % → stagege III III biopsybiopsy: : thickening of glomerular basal thickening of glomerular basal

membranemembrane, , mesangium expansionmesangium expansion GFRGFR still still ↑ (↑ (byby 20-50 %) 20-50 %) normal urine albumin excretionnormal urine albumin excretion posposssibiblele microalbuminuri microalbuminuriaa (tran (transsitoritoryy!)!) normal BPnormal BP

Mogensen classification (3)Mogensen classification (3)

StaStagege III ( III (early diabetic nephropathyearly diabetic nephropathy)) 6-15 6-15 yrs from diagnosis of DMyrs from diagnosis of DM

blood glucose and BP comtrolblood glucose and BP comtrol → → stops/decreases stops/decreases

progressionprogression

persistent microalbuminuripersistent microalbuminuriaa (30-300 mg (30-300 mg/24 hrs)/24 hrs)

GGFRFR stillstill , , but decreases by but decreases by 3-5 ml3-5 ml/min/yr/min/yr

BP normal or mildlyBP normal or mildly ( ( by by 3 mmHg3 mmHg/yr/yr))

Mogensen classification (4)Mogensen classification (4)

StaStagege IV ( IV (clinical diabetic nephropathyclinical diabetic nephropathy)) 15-25 15-25 yrsyrs after onset of DMafter onset of DM proteinuriaproteinuria (albuminuri (albuminuriaa > > 300 mg300 mg/24 hrs)/24 hrs) GFRGFR progres progressivelysively ( (byby 8-12 ml 8-12 ml/min/yr)/min/yr) 3 sub-classes:3 sub-classes:

early (GFR > 130 ml/min)early (GFR > 130 ml/min) intermediate (GFR < 100 ml/min)intermediate (GFR < 100 ml/min) advanced (GFR < 70 ml/min)advanced (GFR < 70 ml/min)

BP BP (by 5 mmHg/yr)(by 5 mmHg/yr)

Mogensen classification (5)Mogensen classification (5)

StaStagege V ( V (end-stage renal failureend-stage renal failure)) 25-30 25-30 yrs after onset of DMyrs after onset of DM variable proteinuriavariable proteinuria urine albumin excretionurine albumin excretion < 10 g/24 hrs< 10 g/24 hrs GFR < 10 ml/minGFR < 10 ml/min BP constantly BP constantly Microscope: important glomerular modificationsMicroscope: important glomerular modifications

ScreeninScreening for g for diabeticdiabetic nenephphropatropathyhy

Annual determining ofAnnual determining of microalbuminurimicroalbuminuriaa:: Type 1 DMType 1 DM::

from pubertyfrom puberty 5 yrs after diagnosis5 yrs after diagnosis

Type 2 DMType 2 DM : : from diagnosisfrom diagnosis

How?How? minimum 3 minimum 3 samples in 3-6 monthssamples in 3-6 months avoidavoid condi conditionstions that can produce transient urinary albumin that can produce transient urinary albumin

excretionsexcretions persistent microalbuminuripersistent microalbuminuriaa = = 2 2 out of out of 3 3 results ofresults of 30-300 30-300

mg/24 mg/24 hrshrs, 20-200 µg/min , 20-200 µg/min or urine albumin/creatinineor urine albumin/creatinine = 30- = 30-300 mg/g300 mg/g

TratamentTratament of of diabeticdiabetic nenephphropatropathyhy

ObObjectivesjectives:: Good Good glglyycemiccemic c controlontrol TTreat high BPreat high BP DietDiet TrTreat dyslipidemiaeat dyslipidemia Prevent / treat related comorbiditiesPrevent / treat related comorbidities TrTreat renal anemiaeat renal anemia PPrevent / treat renal bone diseaserevent / treat renal bone disease

TTreating hypertension in patients reating hypertension in patients

with diabetic nephropathywith diabetic nephropathy

Non-phNon-pharmacologicarmacologicallyally:: exerciseexercise weight lossweight loss low-sodium dietlow-sodium diet low-protein dietlow-protein diet smoking cessationsmoking cessation avoid alcoholavoid alcohol coffeecoffee

DrugsDrugs:: ACE inhibitorsACE inhibitors ARBsARBs diureticsdiuretics Calcium blockersCalcium blockers beta-blockersbeta-blockers -adrenergic blockers-adrenergic blockers

3. Diabetic neuropathy3. Diabetic neuropathy

Acute reversibleAcute reversible hyperglycemic neuropathyhyperglycemic neuropathy

PersistentPersistent SymmetricalSymmetrical

Distal symmetrical neuropathy (chronic Distal symmetrical neuropathy (chronic sensory and autonomic polyneuropathy)sensory and autonomic polyneuropathy)

Acute painful neuropathyAcute painful neuropathy Focal and multifocalFocal and multifocal

Mononeuropathies (diabetic amyotrophy)Mononeuropathies (diabetic amyotrophy)

Symptoms in distal symmetrical Symptoms in distal symmetrical neuropathyneuropathy

Asymptomatic in someAsymptomatic in some NumbnessNumbness Altered sensationAltered sensation

paraesthesiaeparaesthesiae allodyniaallodynia

PainPain

Signs in distal symmetrical Signs in distal symmetrical neuropathyneuropathy

NoneNone Loss ofLoss of

vibration sensevibration sense pin prickpin prick touchtouch temperaturetemperature joint position sensejoint position sense

Wasting and weakness rareWasting and weakness rare Autonomic involvement:Autonomic involvement:

warm feet (dilated arteriovenous shunts)warm feet (dilated arteriovenous shunts) dry feet (absent sweating)dry feet (absent sweating)

ComplicationsComplications ulcerulcer oedemaoedema Charcot arthropathy Charcot arthropathy

Aetiology of foot ulceration in diabetic Aetiology of foot ulceration in diabetic

patientspatients Neuropathy

Autonomic Motor Sensory

A-V ShuntingAbsent sweati

ng

Reduced

tissue nutritio

n

Ischaemia

Micro-vascula

r disease

Arterial

disease

Abnormal foot

posture (raised arch,

clawed toes)

Reduced pain

sensation

Increased pressure loading

-Charcot joint

- Orthopaedic

deformity

Callus formation

Ulceration

Trauma

Infection

Charcot arthropathyCharcot arthropathy

severe neuropathysevere neuropathy long-standing long-standing

diabetesdiabetes initiating event = initiating event =

injury, causing bone injury, causing bone fracturefracture

gross deformity gross deformity cubic footcubic foot acute Charcot footacute Charcot foot