Association between plasma triglycerides and high-density lipoprotein cholesterol and microvascular kidney disease and retinopathy in type 2 diabetes mellitus: a global case-control study in 13 countries

Circulation. 2014 Mar 4;129(9):999-1008. doi: 10.1161/CIRCULATIONAHA.113.002529. Epub 2013 Dec 18.


Background: Microvascular renal and retinal diseases are common major complications of type 2 diabetes mellitus. The relation between plasma lipids and microvascular disease is not well established.

Methods and results: The case subjects were 2535 patients with type 2 diabetes mellitus with an average duration of 14 years, 1891 of whom had kidney disease and 1218 with retinopathy. The case subjects were matched for diabetes mellitus duration, age, sex, and low-density lipoprotein cholesterol to 3683 control subjects with type 2 diabetes mellitus who did not have kidney disease or retinopathy. The study was conducted in 24 sites in 13 countries. The primary analysis included kidney disease and retinopathy cases. Matched analysis was performed by use of site-specific conditional logistic regression in multivariable models that adjusted for hemoglobin A1c, hypertension, and statin treatment. Mean low-density lipoprotein cholesterol concentration was 2.3 mmol/L. The microvascular disease odds ratio increased by a factor of 1.16 (95% confidence interval, 1.11-1.22) for every 0.5 mmol/L (≈1 quintile) increase in triglycerides or decreased by a factor of 0.92 (0.88-0.96) for every 0.2 mmol/L (≈1 quintile) increase in high-density lipoprotein cholesterol. For kidney disease, the odds ratio increased by 1.23 (1.16-1.31) with triglycerides and decreased by 0.86 (0.82-0.91) with high-density lipoprotein cholesterol. Retinopathy was associated with triglycerides and high-density lipoprotein cholesterol in matched analysis but not significantly after additional adjustment.

Conclusions: Diabetic kidney disease is associated worldwide with higher levels of plasma triglycerides and lower levels of high-density lipoprotein cholesterol among patients with good control of low-density lipoprotein cholesterol. Retinopathy was less robustly associated with these lipids. These results strengthen the rationale for studying dyslipidemia treatment to prevent diabetic microvascular disease.

Keywords: diabetes mellitus; diabetic retinopathy; epidemiology; kidney; lipids; risk factors.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / blood
  • Case-Control Studies
  • Cholesterol, HDL / blood*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetic Nephropathies / blood
  • Diabetic Nephropathies / epidemiology*
  • Diabetic Nephropathies / etiology
  • Diabetic Retinopathy / blood
  • Diabetic Retinopathy / epidemiology*
  • Diabetic Retinopathy / etiology
  • Dyslipidemias / prevention & control
  • Female
  • Humans
  • Hypolipidemic Agents / therapeutic use
  • Incidence
  • Internationality*
  • Male
  • Microvessels / physiopathology
  • Middle Aged
  • Multivariate Analysis
  • Risk Factors
  • Triglycerides / blood*


  • Biomarkers
  • Cholesterol, HDL
  • Hypolipidemic Agents
  • Triglycerides