Association Between Plasma Triglycerides and HDL-Cholesterol and Microvascular Kidney Disease and Retinopathy in Type 2 Diabetes: A Global Case-Control Study in 13 Countries

Study Questions:

Microvascular renal and retinal diseases are common major complications of type 2 diabetes. Is there a relationship between plasma lipids and microvascular disease?

Methods:

The study utilized a case-control design in 13 countries. Cases and controls had type 2 diabetes, were at least 40 years old, and had low-density lipoprotein cholesterol (LDL-C) ≤3.4 mmol/L (130 mg/dl). Cases were 2,535 patients with average duration of diabetes of 14 years, 1,891 having kidney disease (proteinuria >300 mg/L, albuminuria [albumin/creatinine ratio ≥30 μg/mg in a morning urine sample or >30 mg/24 hours] or estimated glomerular filtration rate <60 ml/min/1.73 m2), and 1,218 retinopathy (laser treatment for diabetic retinopathy or defined by standard qualitative measures). The cases were matched for diabetes duration, age, sex, and LDL-C, with 3,683 controls without kidney disease or retinopathy. The primary analysis included one or both of kidney disease and retinopathy cases. Matched analysis was performed using site-specific conditional logistic regression in multivariable models that adjusted for hemoglobin A1c, hypertension, and statin treatment.

Results:

Mean age was 65 years and 58% were male; fibrates were used in 7.4% and statins in 51%, with no difference between groups. The microvascular disease odds ratio (OR) increased by a factor of 1.16 (95% confidence interval, 1.11-1.22) for every 0.5 mmol/L (44 mg/dl and approximately 1 quintile) increase in triglycerides; or decreased by a factor of 0.92 (0.88, 0.96) for every 0.2 mmol/L (7.7 mg/dl and approximately 1 quintile) increase in high-density lipoprotein cholesterol (HDL-C). For kidney disease, the OR increased by 1.23 (1.16, 1.31) with triglycerides and decreased by 0.86 (0.82, 0.91) with HDL-C. Retinopathy was associated with triglycerides and HDL-C in matched analysis, but not significantly after additional adjustment.

Conclusions:

The authors concluded that diabetic kidney disease is associated worldwide with higher levels of plasma triglycerides and lower levels of HDL-C among patients with good control of LDL-C. Retinopathy was less robustly associated with these lipids.

Perspective:

The ability to demonstrate similar findings utilizing over 24 sites in 13 countries increases the generalizability of the findings, but markedly increases the dependence of the accuracy of conclusions on complicated statistical analysis. Nevertheless, as the authors suggest, the results strengthen the rationale for studying dyslipidemia treatment to prevent diabetic microvascular disease.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Hypertriglyceridemia, Lipid Metabolism, Nonstatins, Hypertension

Keywords: Lipids, Diabetes Mellitus, Type 2, Proteinuria, Diabetic Nephropathies, Hemoglobin A, Glycosylated, Cholesterol, Dyslipidemias, Diabetic Retinopathy, Case-Control Studies, Glomerular Filtration Rate, Triglycerides, Hypertension


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