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Chronic Complicationsof

Diabetes Mellitus

By: Ismah Haron

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Classification

DM

Microvascular

- Retinopathy

- Nephropathy

- Neuropathy

Macrovascular

- Coronary heart disease

- Cerebrovascular disease

Both

- Diabetic foot

- Erectile dysfunction

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Mechanisms

1. ↑ formation of advanced glycosylation end products (AGEs)

2. ↑ sorbitol pathway

3. Activation of protein kinase C (PKC)

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↑ intracellular glucose

Interaction of glucose with amino acidsvia nonenzymatic glycosylation Advanced glycosylation end products

↑ AGEs

• cross-link proteins eg.collagen• accelerate atherosclerosis• promote glomerular dysfunction• induce endothelial dysfunction

1. Hyperglycemia ↑ AGEs synthesis

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2. Hyperglycemia ↑ glucose metabolism via sorbitol pathway

Intracellular glucose ↑ promotes conversion to sorbitol

via aldose reductase

↑ Sorbitol

• alters redox potential

• ↑ cellular osmolality

• generates reactive O2 species

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3. PKC Activation

Hyperglycemia ↑ DAG formation PKC activation

Effects of PKC activation :

• production of vascular endothelial growth factor(VEGF) neovascularization diabetic retinopathy

• ↑ activity of vasoconstrictor & ↓ activity of vasodilator in endothelial tissues

• production of molecule procoagulant ↓ fibrinolysis vascular occlusion

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Retinopathy

• Capillary endothelial change vascular leak microaneurysms capillary occlusion local hypoxia & ischemia new vessels formation

• Visual acuity and eye fundus examination

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Nephropathy

• Proteinuria detected on urine dipstick or• Microalbuminuria • Renin-angiotensin blockers• Refer to nephrologists if serum

creatinine > 200 µmol/L

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Neuropathy

• Light pressure sensation• Vibration• Ankle jerk• Pin prick

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5 neuropathies in DM: Distal symmetrical polyneuropathy, proximal asymmetrical neuropathy, mononeuritis multiplex, radiculopathy

and autonomic neuropathy

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Coronary heart disease

• Association with DM explained by concomitant risk factors

• Resting ECG• Cardiovascular risk assessment tool

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Diabetic foot

• Peripheral neuropathy• Vasculopathy- Claudication- Examine dorsalis pedis & posterior tibial

pulses

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Erectile dysfunction

• Vasculopathy, autonomic neuropathy and/or psychological factors

• Risk factor: ageing, longer duration of having DM, poor glycemic control, smoking and HPT

• Screen adult male > 40 years old• IIEF questionnaire

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Source: Ministry of Health Malaysia

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THANK YOUThe end.