Chronic Complications

By: Siti Nurulismah Bt Che Haron

Classification
DM

Microvascular

Macrovascular

Both

- Retinopathy - Nephropathy - Neuropathy

- Coronary heart disease - Cerebrovascular disease

- Diabetic foot - Erectile dysfunction

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Mechanisms
1. 2. 3. formation of advanced glycosylation end products (AGEs) sorbitol pathway Activation of protein kinase C (PKC)

1. Hyperglycemia AGEs synthesis

intracellular glucose Interaction of glucose with amino acids via nonenzymatic glycosylation Advanced glycosylation end products

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

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

Retinopathy
Capillary endothelial change vascular leak microaneurysms capillary occlusion local hypoxia & ischemia new vessels formation Visual acuity and eye fundus examination

Nephropathy
Proteinuria detected on urine dipstick or Microalbuminuria Renin-angiotensin blockers Refer to nephrologists if serum creatinine > 200 mol/L

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 11 and autonomic neuropathy

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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The end.

THANK YOU
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