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Understanding Diabetic Vascular Disease: Genetic Influences and Accelerators

Explore the genetic influences and independent accelerators contributing to diabetic vascular disease, including factors like hyperglycemia, metabolic influences, and haemodynamic factors. Learn about the pathways involved and key markers to monitor for early detection and management.

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Understanding Diabetic Vascular Disease: Genetic Influences and Accelerators

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  1. Genetic InfluencesIndependent Accelerators eg hypertension, lipids, smoking Hyperglycaemia Metabolic FactorsHaemodynamic Factors Glucose Toxicity Angiotensin II/renin angiotenin system Glycation Endothelin Polyol Pathway Nitric oxide Hexosamine Pathway Growth Factors / CytokinesIntracellular Factors TGF-β,VEGF, AGII, DAG-PCK, MAPK NFĸB CTGF, GH, IGF-1 Diabetic Vascular Disease

  2. Hyperglycaemia Increased mitochondrial ROS DNA strand breaks Activation of PARP Inhibition of GAPDH Accumulation of glycolytic intermediates upstream of GAPDH Increased polyol and hexosamine flux, glycation, DAG-PKC

  3. Normoalbuminuria 30-50 % 50 % Microalbuminuria Proteinuria ESRD Increasing blood pressure and cardiovascular risk 20-30 % 30-50%

  4. Insulin Resistance Hypertension High TG Low HDL Central Obesity Microvascular complications Cardiovascular Risk Endothelial Dysfunction Inflammation

  5. Prevalence (% or n) n n n n n Proteinuria Microalbuminuria Neuropathy BP >140/80 mmHg Serum creatinine >176 µmol/l Progression of retinopathy Proliferative retinopathy Laser treatment

  6. Annual, in stable glucose control Serum creatinine, calculate eGFR Early morning urine sample Dip-stick for proteinuria ≥2++ <2 ++ Urine albumin:creatinine ratio 2.5 – 30 mg/mmol (men) 3.5 – 30 mg/mmol (women) Urine Protein:creatinine ratio Yes Repeat x2 within 3 months No Repeat annually

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