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Diabetes Complications

DG van Zyl

The Ticking Clock

Different Diabetes Complications

Macro vascular Micro vascular Neuropathy Infections

Mechanisms

Hyperglycemia Tissue damage

*Repeated acute changes in cellular metabolism

**Cumulative long term changes in stable macromolecules

Genetic susceptibility

Independent accelerating factors

Macro vascular Complications

Macro-vascular Complications

Ischemic heart disease Cerebrovascular disease Peripheral vascular disease

Diabetic patients have a 2 to 6 times higher risk fordevelopment of these complications than thegeneral population

Macro-vascular Complications

The major cardiovascular risk factors in the non-diabetic population (smoking, hypertension and hyperlipidemia) also operate in diabetes, but the risks are enhanced in the presence of diabetes.

Overall life expectancy in diabetic patients is 7 to 10 years shorter than non-diabetic people.

Macro-vascular Disease

Once clinical macro-vascular disease develops in diabetic patients they have a poorer prognosis for survival than normoglycemic patients with macrovascular disease

The protective effect females have for the development of vascular disease are lost in diabetic females

CAD Morbidity and Mortality in Type 2 DM Framingham Data: 20

year follow-up:Age 45-74: 2-3 fold increase in

clinically evident atherosclerotic disease in diabetics

women diabetics=male diabetics in terms of CAD mortality

Multiple Risk Factor Intervention Trial (MRFIT) 5000 men with type 2

DM Followed for 12 years Men with type 2 DM

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

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

Cardiovascular Death Rates: MRFIT data

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

Risk of MI in Diabetes

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

Plasma Glucose as Independent Risk Factor

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

Glycemic Control to Reduce CADDCCT 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)

Effect of HypertensionMortality vs systolic blood pressure

0

10

20

30

40

50

60

70

110 120 130 140 150 160

Systolic Blood pressure (mmHg)

Ten

Year

Mor

talit

y (p

er 1

000)

Non-diabetic

Diabetic

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

Hypertension in Type 1 and 2 Diabetes

Type 1

Develop after several years of DM

Ultimately affects ~30% of patients

Type 2

Mostly present at diagnosis

Affects at least 60% of patients

Pathophysiology of hypertension

Type 1 DM

Secondary tonephropathy

Activation of the RAAS

Type 2 DM

HyperinsulinemiaSecondary to insulin

resistanceActivation of the

sympathetic nervous system

Goals of Treatment of Hypertension

Lower target for diabetic patients than non-diabetic patients:

130/85 vs. 140/90

UKPDS 38. BMJ 1998;317:703-713HOT. Lancet 1998;351:1755-1762

Effect of Cholesterol

Serum cholesterol vs Mortality

010203040506070

4 5 6 7

s-Cholesterol (mmol/L)

Ten

Year

Mor

talit

y (p

er

1000

) Non-diabeticDiabetic

Dyslipidaemia in DM

Most common abnormality is s HDL and s Triglyserides

A low HDL is the most constant predictor of CV disease in DM

Target lipid values: LDL <2.6 mmol/l, HDL >1.15 mmol/l, TG < 2.5 mmol/l

Micro vascular Complications

Eye Complications

Cataracts

Non enzymatic glycation of lens protein and subsequent cross linking

Sorbitol accumulation could also lead to osmotic swelling of the lens but evidence of involvement in cataract formation is less strong

Eye Complications

Retinopathy (stages)BackgroundPre-proliferativeProliferativeAdvanced diabetic eye diseaseMaculopathy

Glaucoma

Diabetic Retinopathy (DR)

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

The prevalence increase with the duration of the disease (few within 5 years, 80 – 100% will have some form of DR after 20 years)

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

Background Retinopathy

Micro aneurisms Scattered exudates Hemorrhages(flame

shaped, Dot and Blot) Cotton wool spots

(<5) Venous dilatations

Background retinopathy

Background retinopathy

Pre-Proliferative Retinopathy Rapid increase in

amount of micro aneurisms

Multiple hemorrhages Cotton wool spots

(>5) Venous beading,

looping and duplication

Proliferative retinopathy

Proliferative Retinopathy

New vessels (on disc, elsewhere)

Fibrous proliferation (on disc, elsewhere)

Hemorrhages (preretinal, vitreous)

Panretinal photo-coagulation

Proliferative retinopathy

Vitreous Bleeding

Rubeosis Iridis

Advanced Diabetic Eye Disease

Retinal detachment with or without retinal tears

Rubeosis iridis Neovascular

glaucoma

Maculopathy

Macular edema (focal or diffuse)

Ischaemic maculopathy

Maculopathy

Diabetic Nephropathy (DN)

Diabetes has become the most common cause of end stage renal failure in the US and Europe

About 20 – 30% of patients with diabetes develop evidence of nephropathy

The prevalence of DN is higher in Black Americans than in Whites (Figures for South Africa is not available)

Stages of Diabetic Nephropathy

Stages of DN

Stage I glomerular filtration and kidney hypertrophy

Stage IIu-albumin excretion < 30mg/24h

Stage IIIMicroalbuminuria (30 – 300 mg/24h)

Stages of DN (cont)

Stage IVOvert nephropathy (> 300mg/24h, positive u dipstick)

Stage VESRD characterized by blood urea and creatinine levels, hyperkalaemia and fluid overload

Diabetic Neuropathy

Sensorimotor neuropathy (acute/chronic)Autonomic neuropathyMononeuropathy

SpontaneousEntrapmentExternal pressure palsies

Proximal motor neuropathy

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 neuropathy usually predominates

Complications of Sensorimotor neuropathy

Ulceration (painless) Neuropathic edema Charcot arthropathy Callosities

Autonomic Neuropathy

SymptomaticPostural hypotensionGastroparesisDiabetic diarrheaNeuropathic bladderErectile dysfunctionNeuropathic edemaCharcot arthropathyGustatatory sweating

Subclinical abnormalitiesAbnormal pupillary reflexesEsophageal dysfunctionAbnormal cardiovascular

reflexesBlunted counter-regulatory

responses to hypoglycemia

Increased peripheral blood flow

Mononeuropathies

Cranial nerve palsies (most common are n. IV,VI,VII)

Truncal neuropathy (rare)

Entrapment Neuropathies

Carpal tunnel syndrome (median nerve) Ulnar compression syndrome Meralgia paresthetica (lat cut nerve to the

thigh) Lat Popliteal nerve compression (drop

foot)All the above are more common in diabetic

patients

Proximal Motor Neuropathy

Amyotrophy – most common proximal neuropathy, affects the Quadriceps muscles with weakness and atrophy(synonym: Diabetic Femoral radiculo-neuropathy)

Diabetic Amyotrophy

Thoracoabdominal Radiculopathy

Sudomotor Dysautonomia

Summary

Diabetic neuropathy is a common complication, and result in significant morbidity

Diabetic neuropathy present in numerous ways

Hyperglycemia is the cause of diabetic neuropathy

Summary (cont)

Diabetic neuropathy have bad consequences

Diabetic neuropathy can be prevented in only one way

Once diabetic neuropathy is present it can only be managed symptomatically

Early diagnosis and aggressive management can prevent progression

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 severity and are associated with an increased risk of complications

Infections (cont)

Several aspects of immunity are altered in patients with diabetes

There is evidence that improving glycemic control patients improves immune function

Specific Infections Community acquired

pneumonia Acute bacterial

cystitis Acute pyelonephritis Emphysematous

pyelonephritis Perinephric abscess Fungal cystitis

Necrotizing fasciitis Invasive otitis externa Rhinocerebral

mucormycosis Emphysematous

cholecystitis

Rhino-Cerebral Mucormycosis

Screening and Management Strategy for Diabetes

Complications

Screening for Macrovascular Complications

1. Examine pulses and for cardiovascular disease

2. Lipogram3. ECG4. Blood pressure 1-3 annually4 every visit (quarterly)

Screening for Eye disease

AnnuallyVisual acuity (corrected with pinhole or

lenses)Careful eye examination (noting the clarity

of the lens and any retinal changes (Ophthalmoscopy through dilated pupils)

Screening for Eye disease

When to refer?Severe non-proliferative/proliferative retinopathyMacular edema or exudates in close proximity to

the maculaCataractUnexplained reduction in visual acuity

Screening for Nephropathy

AnnuallyDo one of the following:

u Albumin:Creatinine ratio (spot sample)24h u Albumin excretion rateEarly morning Albumin concentration

(spot sample)Dipstick for Microalbuminuria

If 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 the microalbumin range

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 aggressive intervention to reduce all cardiovascular risk factors

Screening Tests for Microalbuminuria

Category24h u

collection(mg/24h)

Timed collection(mg/min)

Spot collection(mg/mg creat)

Normal 30 20 30

Microalbuminuria 30 - 299 20 - 199 30 - 299

Albuminuria Overt 300 200 300

Who to Screen For Microalbuminuria

Type 1 DiabetesBegin with pubertyAfter 5 years

duration of diseaseShould be done

annually there after

Type 2 DiabetesStart screening at

the Diagnosis of diabetes

Should be done annually there after

Management of Nephropathy

Improvement of glycemic control Treatment of hypertension Treatment with angiotensin converting

enzyme inhibitors Restriction of dietary intake of proteinOnce persistent elevation in u-Albumin isfound refer to a Internist or Nephrologist

Screening for Neuropathy 128 Hz tuning fork for

testing of vibration perception

10g Semmers monofilament

The main reason is toidentify patients at riskfor development ofdiabetic foot

Using of the Monofilament

Management of Neuropathy

Burning pain – TADs / Capsaicin Lancinating pain – Anticonvulsants / TAD /

Capsaicin Painful cramps – Quinidine sulphate Restless legs - Clonazepam

Do’s 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

Conclusion

This is just an outline of the major diabetic complications, and doesn't aim to be comprehensive

All complications are preventable with good glycaemic control

The progression of most complications can be halted if detected early and appropriate therapy instituted