Chronic complications

1. Chronic Complications
of
Diabetes Mellitus
By: Ismah Haron
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2. Classification
DM
Microvascular
- Retinopathy
- Nephropathy
- Neuropathy
Macrovascular
- Coronary heart
disease
- Cerebrovascular
disease
Both
- Diabetic foot
- Erectile
dysfunction
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3. Mechanisms
1. ↑ formation of advanced glycosylation end products
(AGEs)
2. ↑ sorbitol pathway
3. Activation of protein kinase C (PKC)
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4. ↑ 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
1. Hyperglycemia ↑ AGEs synthesis
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5. 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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6. 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 6

7. 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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8. 8

9. Nephropathy
• Proteinuria detected on urine dipstick or
• Microalbuminuria
• Renin-angiotensin blockers
• Refer to nephrologists if serum
creatinine > 200 µmol/L
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10. Neuropathy
• Light pressure sensation
• Vibration
• Ankle jerk
• Pin prick
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11. 5 neuropathies in DM: Distal symmetrical polyneuropathy, proximal
asymmetrical neuropathy, mononeuritis multiplex, radiculopathy
and autonomic neuropathy
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12. Coronary heart disease
• Association with DM explained by
concomitant risk factors
• Resting ECG
• Cardiovascular risk assessment tool
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13. Diabetic foot
• Peripheral neuropathy
• Vasculopathy
- Claudication
- Examine dorsalis pedis & posterior tibial
pulses
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14. 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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15. Source:
Ministry of Health Malaysia
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16. THANK YOU
The end.
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