chronic complications of diabetes mellitus

7/30/2019 Chronic complications of diabetes mellitus

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Diabetes Complications

MUHAMMAD ZAMAN HABIB

FINAL YEAR MBBS

NISHTAR MEDICAL COLLEGE

MULTAN


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The Ticking Clock


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Different Diabetes Complications

Macro vascular

Micro vascular

Neuropathy

Infections


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Mechanisms

Hyperglycemia Tissue damage

*Repeated acute changes

in cellular metabolism

**Cumulative long termchanges in stable

macromolecules

Genetic susceptibility

Independent accelerating factors


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Macro vascular Complications


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Macro-vascular Complications

Ischemic heart disease

Cerebrovascular disease

Peripheral vascular disease

Diabetic patients have a 2 to 6 times higher risk for

development of these complications than thegeneral population


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Macro-vascular Complications

The major cardiovascular risk factors in the

non-diabetic population (smoking,

hypertension and hyperlipidemia) alsooperate in diabetes, but the risks are

enhanced in the presence of diabetes.

Overall life expectancy in diabetic patients is7 to 10 years shorter than non-diabetic

people.


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Macro-vascular Disease

Once clinical macro-vascular disease

develops in diabetic patients they have a

poorer prognosis for survival thannormoglycemic patients with

macrovascular disease

The protective effect females have for thedevelopment of vascular disease are lost

in diabetic females


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CAD Morbidity and Mortality in

Type 2 DM

Framingham Data: 20year follow-up:Age45-74: 2-3 fold increase in

clinically evidentatheroscleroticdisease in diabetics

womendiabetics=malediabetics in terms ofCAD mortality

Multiple Risk FactorIntervention Trial(MRFIT) 5000 men with type 2

DM

Followed for 12 years

Men with type 2 DM

had absolute risk ofCAD-related death 3times higher than non-diabetic cohort


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Risk Factor Clustering in Diabetes

Type 2 Diabetes at Diagnosis:

50% have hypertension

30% have dyslipidemia UKPDS:

Prospective study

Newly detected type 2 DM:

335 with CAD, 8 year follow-up

Associated with elevated LDL-C, low levels of HDL-C,

systolic hypertension


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Cardiovascular Death Rates:

MRFIT data

Stamler J., et al Diabetes Care: 16: 434-444


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Risk of MI in Diabetes

Haffner, SM et al NEJM: 339: 229-234


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Plasma Glucose as Independent

Risk Factor

Andersson, DK et al. Diabetes Care 18: 1534-1543


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Glycemic Control to Reduce CAD

DCCT trial:

1441 patients, type 1 diabetes

Randomized to intensive

glycemic control vs.

conventional therapy

Monitored prospectively for 6.5

years

Results:

Less retinopathy by 50% Macrovascular complications:

41% reduction (not statistically

significant)

-small number of events in

young patient cohort

UKPDS:

3867 patients with

newly diagnosed type 2

DM

Intensive vs.

Conventional therapy

10 year follow-up

Microvascular

endpoints improved Trend only towards

reduced incidence of MI

( p=0.052)


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Effect of Hypertension

Mortality vs systolic blood pressure

0

10

20

30

40

50

60

70

110 120 130 140 150 160

Systolic Blood pressure

(mmHg)

Ten

YearMortality(per1000)

Non-diabetic

Diabetic


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Why worry about Hypertension in

Diabetic patients

Treating hypertension can reduce the risk

of:

Death 32%

Microvascular disease 37%

Stroke 44%

Heart failure 56%

UKPDS BMJ 1998;317:703 - 713


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Hypertension in Type 1 and 2

Diabetes

Type 1

Develop after severalyears of DM

Ultimately affects ~30%

of patients

Type 2

Mostly present atdiagnosis

Affects at least 60% of

patients


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Pathophysiology of hypertension

Type 1 DM

Secondary tonephropathy

Activation of theRAAS

Type 2 DM

Hyperinsulinemia

Secondary to insulin

resistance

Activation of thesympathetic nervous

system


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Goals of Treatment of Hypertension

Lower target for diabetic patients than non-

diabetic patients:

130/85 vs. 140/90

UKPDS 38. BMJ 1998;317:703-713

HOT. Lancet 1998;351:1755-1762


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Effect of Cholesterol

Serum cholesterol vs Mortality

0

10

20

30

40

5060

70

4 5 6 7

s-Cholesterol (mmol/L)

Ten

YearMortality

(per

1000)

Non-diabetic

Diabetic


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Dyslipidaemia in DM

Most common abnormality is s HDL and

s Triglyserides

A low HDL is the most constant predictorof CV disease in DM

Target lipid values: LDL 1.15 mmol/l, TG < 2.5 mmol/l


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Micro vascular Complications


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Eye Complications

Cataracts

Non enzymatic glycation of lens protein and

subsequent cross linking

Sorbitol accumulation could also lead to osmoticswelling of the lens but evidence of involvement

in cataract formation is less strong
http://www.eyesearch.com/cloudy.vision.jpg


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Eye Complications

Retinopathy (stages)

Background

Pre-proliferative

Proliferative

Advanced diabetic eye disease

Maculopathy

Glaucoma


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Diabetic Retinopathy (DR)

DR is the leading cause of blindness in theworking population of the Western world

The prevalence increase with the durationof the disease (few within 5 years, 80100% will have some form of DR after 20years)

Maculopathy is most common in type 2patients and can cause severe visual loss


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Background Retinopathy

Micro aneurisms

Scattered exudates

Hemorrhages(flameshaped, Dot and Blot)

Cotton wool spots

(


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Background retinopathy


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Pre-Proliferative Retinopathy

Rapid increase inamount of microaneurisms

Multiple hemorrhages

Cotton wool spots(>5)

Venous beading,looping andduplication

Proliferative retinopathy


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Proliferative Retinopathy

New vessels (on disc,

elsewhere)

Fibrous proliferation(on disc, elsewhere)

Hemorrhages

(preretinal, vitreous)

Panretinal photo-coagulation


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Proliferative retinopathy


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Vitreous Bleeding


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Rubeosis Iridis


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Advanced Diabetic Eye Disease

Retinal detachment

with or without retinal

tears

Rubeosis iridis

Neovascular

glaucoma


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Maculopathy

Macular edema (focal

or diffuse)

Ischaemicmaculopathy


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Maculopathy


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Diabetic Nephropathy (DN)

Diabetes has become the most commoncause of end stage renal failure in the US

and EuropeAbout 20 30% of patients with diabetes

develop evidence of nephropathy

The prevalence of DN is higher in BlackAmericans than in Whites (Figures forSouth Africa is not available)


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Stages of Diabetic Nephropathy


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Stages of DN

Stage I

glomerular filtration and kidney

hypertrophyStage II

u-albumin excretion < 30mg/24h

Stage III

Microalbuminuria (30 300 mg/24h)


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Stages of DN (cont)

Stage IV

Overt nephropathy (> 300mg/24h, positive

u dipstick)Stage V

ESRD characterized by blood urea and

creatinine levels, hyperkalaemia and fluidoverload


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Diabetic Neuropathy

Sensorimotor neuropathy (acute/chronic)

Autonomic neuropathy

Mononeuropathy

Spontaneous

Entrapment

External pressure palsies

Proximal motor neuropathy


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Sensorimotor Neuropathy

Patients may be asymptomatic / complain

of numbness, paresthesias, allodynia or

pain Feet are mostly affected, hands are

seldom affected

In Diabetic patients sensory neuropathyusually predominates

C li ti f S i t


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Complications of Sensorimotor

neuropathy

Ulceration (painless)

Neuropathic edema

Charcot arthropathy Callosities


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Autonomic Neuropathy

Symptomat ic

Postural hypotension

Gastroparesis

Diabetic diarrhea

Neuropathic bladder

Erectile dysfunction

Neuropathic edemaCharcot arthropathy

Gustatatory sweating

Subc l inical abno rmali t ies

Abnormal pupillary reflexes

Esophageal dysfunction

Abnormal cardiovascular

reflexes

Blunted counter-regulatory

responses to

hypoglycemia

Increased peripheral blood

flow


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Mononeuropathies

Cranial nerve palsies

(most common are n.

IV,VI,VII)

Truncal neuropathy

(rare)


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Entrapment Neuropathies

Carpal tunnel syndrome (median nerve)

Ulnar compression syndrome

Meralgia paresthetica (lat cut nerve to thethigh)

Lat Popliteal nerve compression (drop

foot)All the above are more common in diabeticpatients


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Proximal Motor Neuropathy

Amyotrophy most common proximal

neuropathy, affects the Quadriceps

muscles with weakness and atrophy(synonym: Diabetic Femoral radiculo-

neuropathy)


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Diabetic Amyotrophy


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Thoracoabdominal Radiculopathy


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Sudomotor Dysautonomia


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Summary

Diabetic neuropathy is a common

complication, and result in significant

morbidity Diabetic neuropathy present in numerous

ways

Hyperglycemia is the cause of diabeticneuropathy


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Summary (cont)

Diabetic neuropathy have badconsequences

Diabetic neuropathy can be prevented inonly one way

Once diabetic neuropathy is present it canonly be managed symptomatically

Early diagnosis and aggressivemanagement can prevent progression


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Infections

The association between diabetes and

increased susceptibility to infection in general is

not supported by strong evidence

However, many specific infections are more

common in diabetic patients and some occur

almost exclusively in them

Other infections occur with increased severityand are associated with an increased risk of

complications


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Infections (cont)

Several aspects of immunity are altered in

patients with diabetes

There is evidence that improving glycemiccontrol patients improves immune function


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Specific Infections

Community acquiredpneumonia

Acute bacterial

cystitis

Acute pyelonephritis

Emphysematous

pyelonephritis Perinephric abscess

Fungal cystitis

Necrotizing fasciitis

Invasive otitis externa

Rhinocerebralmucormycosis

Emphysematous

cholecystitis


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Rhino-Cerebral Mucormycosis


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Screening and Management

Strategy for Diabetes

Complications

Screening for Macrovascular


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Screening for Macrovascular

Complications

1. Examine pulses and for cardiovascular

disease

2. Lipogram3. ECG

4. Blood pressure

1-3 annually

4 every visit (quarterly)


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Screening for Eye disease

Annually

Visual acuity (corrected with pinhole or

lenses)Careful eye examination (noting the clarity

of the lens and any retinal changes

(Ophthalmoscopy through dilated pupils)


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Screening for Eye disease

When to refer?

Severe non-proliferative/proliferative retinopathy

Macular edema or exudates in close proximity tothe macula

Cataract

Unexplained reduction in visual acuity


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Screening for Nephropathy

Annually

Do one of the following:

u Albumin:Creatinine ratio (spot sample)

24h u Albumin excretion rate

Early morning Albumin concentration

(spot sample)

Dipstick for MicroalbuminuriaIf positive the test must be repeated twice in the ensuing 3 months. Microalbuminuria

with incipient nephropathy is diagnosed if 2 or more of the tests are within themicroalbumin range


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Microalbuminuria

Increased risk for overt nephropathy

Increased cardiovascular mortality

Increased risk of Retinopathy

Increased all-cause mortality

Thus

Microalbuminuria is an indication for screening

for possible vascular disease and aggressiveintervention to reduce all cardiovascular riskfactors

Screening Tests for


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Screening Tests for

Microalbuminuria

Category24h u

collection(mg/24h)

Timedcollection(mg/min)

Spotcollection

(mg/mgcreat)

Normal 30 20 30

Microalbuminuria

30 - 299 20 - 199 30 - 299

AlbuminuriaOvert

300 200 300

Who to Screen For


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Who to Screen For

Microalbuminuria

Type 1 Diabetes

Begin with puberty

After 5 yearsduration of disease

Should be done

annually there after

Type 2 Diabetes

Start screening at

the Diagnosis ofdiabetes

Should be done

annually there after


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Management of Nephropathy

Improvement of glycemic control

Treatment of hypertension

Treatment with angiotensin convertingenzyme inhibitors

Restriction of dietary intake of protein

Once persistent elevation in u-Albumin is

found refer to a Internist or Nephrologist


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Screening for Neuropathy

128 Hz tuning fork fortesting of vibrationperception

10g Semmersmonofilament

The main reason is to

identify patients at risk

for development of

diabetic foot


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Using of the Monofilament


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Management of Neuropathy

Burning pain TADs / Capsaicin

Lancinating pain Anticonvulsants / TAD /

Capsaicin Painful cramps Quinidine sulphate

Restless legs - Clonazepam


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Dos and Don'ts of foot care

Patient should check feet daily

Wash feet daily

Keep toenails short Protect feet

Always wear shoes

Look inside shoes before

putting them on Always wear socks

Break in new shoes gradually


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Conclusion

This is just an outline of the major diabeticcomplications, and doesn't aim to becomprehensive

All complications are preventable withgood glycaemic control

The progression of most complications

can be halted if detected early andappropriate therapy instituted

chronic complications of diabetes mellitus

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