Low HDL Cholesterol and the Risk of Diabetic Nephropathy and Retinopathy

Results of the ADVANCE study

  1. on behalf of the ADVANCE Collaborative Group
  1. 1The Heart Research Institute, Sydney, New South Wales, Australia
  2. 2Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia
  3. 3The George Institute for Global Health, University of Sydney, Sydney, New South Wales, Australia
  4. 4School of Public Health, Monash University, Melbourne, Victoria, Australia
  5. 5Department of Cardiology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
  6. 6Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, the Netherlands
  7. 7Department of Epidemiology, University Medical Centre Groningen, Groningen, the Netherlands
  8. 8Department of Clinical Epidemiology and Biostatistics, Bond University, Gold Coast, Queensland, Australia
  1. Corresponding authors: Sophia Zoungas, szoungas{at}; and Martin K.C. Ng, mkcng{at}


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.

  • Received February 12, 2012.
  • Accepted May 2, 2012.

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  1. Diabetes Care
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