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 A 1c , 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. 1-4 Hyperglycemia and hypertension are major risk factors for the development of microvascular disease.2,4 Intensive control of blood glucose and blood pressure to, or even beyond, currently recommended targets may provide some additional benefits in the prevention of diabetic microvascular disease but is often impossible to achieve because of the associated risks of hypoglycemia or hypotension. 5,6 Therefore, it is necessary to identify other targets and treatments to make progress in slowing the development of diabetic kidney disease and retinopathy.
Clinical Perspective on p 1008Most epidemiological studies have found an association between serum triglycerides and diabetic kidney disease, although less consistently for serum high-density lipoprotein cholesterol (HDL-C). [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] Results diverged among studies on diabetic retinopathy, especially in multivariable analysis. 4,[22][23][24][25][26][27][28][29][30][31][32][33] In randomized, controlled trials, treatment of patients with type 2 diabetes mellitus with fenofibrate, a peroxisome proliferatoractivated receptor-α agonist, reduced the rate of decline in renal function, 25,34 reduced albuminuria, and reduced the requirement for laser treatment of retinopathy. 5,25,34,35 However, it is not clear whether these beneficial effects were caused by improvements in triglycerides or HDL-C or by other biological effects of peroxisome proliferator-activated receptor-α activation.The objective of the present international study was to determine whether low HDL-C or elevated triglycerides levels are associated with diabetic kidney disease and retinopathy independent of established determinants of microvascular disease in patients with type 2 diabetes mellitus with low-density lipoprotein cholesterol (LDL-C) ≤3.4 mmol/L (130 mg/dL).
MethodsThe study used a case-control desi...
