Genetic Influences Independent Acceleratorseg hypertension, lipids, smoking

Hyperglycaemia

Metabolic Factors Haemodynamic FactorsGlucose Toxicity Angiotensin II/renin angiotenin systemGlycation EndothelinPolyol Pathway Nitric oxideHexosamine Pathway

Growth Factors / Cytokines Intracellular FactorsTGF-β, VEGF, AGII, DAG-PCK, MAPK NFĸBCTGF, GH, IGF-1

Diabetic Vascular Disease

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

Normoalbuminuria30-50 % 50 %

Microalbuminuria

Proteinuria

ESRD

30-50 %

20-30 %

Increasing blood pressure and cardiovascular risk

Microvascular complicationsCardiovascular Risk

Insulin Resistance Hypertension

High TGLow HDL

Central Obesity

Endothelial Dysfunction Inflammation

0

10

20

30

40

50Prevalence (% or n)

Progression of re

tinopathy

Proliferat

ive retin

opathy

Laser tr

eatmen

t

BP >140/80 mmHg

Serum creatinine >176 µmol/l

Proteinuria

Microalbuminuria

Neuropathy

nn

n

nn

Annual, in stable glucose control

Serum creatinine, calculate eGFR

Early morning urine sampleDip-stick for proteinuria

≥ 2++ <2 ++

Urine Protein:creatinine ratio Urine albumin:creatinine ratio2.5 – 30 mg/mmol (men)3.5 – 30 mg/mmol (women)

YesRepeat x2 within 3 months

NoRepeat annually