Low HDL cholesterol and the risk of diabetic nephropathy and retinopathy: results of the ADVANCE study

Jamie Morton, Sophia Zoungas, Qiang Li, Anushka A Patel, John Chalmers, Mark Woodward, David S Celermajer, Joline W J Beulens, Ronald P Stolk, Paul Glasziou, Martin K C Ng, ADVANCE Collaborative Group, Jamie Morton, Sophia Zoungas, Qiang Li, Anushka A Patel, John Chalmers, Mark Woodward, David S Celermajer, Joline W J Beulens, Ronald P Stolk, Paul Glasziou, Martin K C Ng, ADVANCE Collaborative Group

Abstract

Objective: Although low HDL cholesterol (HDL-C) is an established risk factor for atherosclerosis, data on HDL-C and the risk of microvascular disease are limited. We tested the association between HDL-C and microvascular disease in a cohort of patients with type 2 diabetes.

Research design and methods: A total of 11,140 patients with type 2 diabetes and at least one additional vascular risk factor were followed a median of 5 years. Cox proportional hazards models were used to assess the association between baseline HDL-C and the development of new or worsening microvascular disease, defined prospectively as a composite of renal and retinal events.

Results: The mean baseline HDL-C level was 1.3 mmol/L (SD 0.45 mmol/L [range 0.1-4.0]). During follow-up, 32% of patients developed new or worsening microvascular disease, with 28% experiencing a renal event and 6% a retinal event. Compared with patients in the highest third, those in the lowest third had a 17% higher risk of microvascular disease (adjusted hazard ratio 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 (1.19 [1.08-1.32], P = 0.0005). There was no association between thirds of HDL-C and retinal events (1.01 [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.

Trial registration: ClinicalTrials.gov NCT00145925.

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