HDL Cholesterol and the Risk of Microvascular Disease of Type 2 Diabetes

Although low HDL Cholesterol (HDL-C) is an established risk factor for atherosclerosis, data on HDL-C and risk of microvascular disease are limited. We tested the association between HDL-C and microvascular disease in a large cohort of patients with type 2 diabetes. METHODS - 11,140 patients with type 2 diabetes and at least one additional vascular risk factor were followed a median of 5 years. Cox proportional hazard models were used to assess the association between baseline HDL-C and development of new or worsening microvascular disease, defined prospectively as a composite of total renal events (new or worsening albuminuria, doubling of creatinine to >200umol/L, need for renal replacement therapy or renal related death) and total retinal events (new proliferative retinopathy, macular oedema, need for photocoagulation therapy or diabetes related blindness). RESULTS - The mean baseline HDL-C level was 1.3 mmol/L (SD 0.45 mmol/L, range 0.1-4.0 mmol/L). During follow-up, 32% of patients developed new or worsening microvascular disease with 28% experiencing a renal event and 6% a retinal event. Compared to patients in the highest third, those in the lowest third had a 17% higher risk of microvascular disease (adjusted HR=1.17, 95% CI 1.06-1.28, p=0.001) after adjustment for potential confounders and regression dilution. This was driven by a 19% higher risk of renal events (adjusted HR=1.19, 95% CI 1.08-1.32, p=0.0005). There was a similar significantly higher risk of developing new microalbuminuria and macroalbuminuria (adjusted HR 1.14, 95% CI 1.03-1.27, p=0.01 and 1.42, 95% CI 1.07-1.87, p=0.01 respectively). There was no association between thirds of HDL-C and retinal events (adjusted HR=1.01, 95% CI 0.82-1.25, p=0.9). CONCLUSIONS - In patients with type 2 diabetes HDL-C level is an independent risk factor for the development of microvascular disease affecting the kidney but not the retina.