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

2. Increased mitochondrial ROS
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

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

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

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

9. 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