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
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