Blood Lipids and Type 2 Diabetes Risk: Can Genetics Help Untangle the Web?

Abstract

Emerging data from randomized trials have shown that a growing number of lipid-lowering drugs appear to influence glycemic control in addition to their hypolipidemic effects. Statins have been shown conclusively in large meta-analyses of randomized trials to increase, albeit modestly, the risk of new-onset type 2 diabetes (T2D) in an apparently dose-dependent manner (1–3). In the Investigation of Lipid Level Management to Understand Its Impact in Atherosclerotic Events (ILLUMINATE) trial, treatment with torcetrapib, a CETP inhibitor that raised HDL cholesterol (HDL-C) concentrations, improved glycemic control (4), but in the Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE) study, niacin treatment, which also raised HDL-C, raised blood glucose and T2D risk (5). In a recent intriguing observational study, notwithstanding the inevitable limitations of its design, patients with familial hypercholesterolemia (FH) appeared less likely to develop T2D (6). Evidence is therefore emerging for a relationship between circulating lipid concentrations and/or their therapeutic/genetic modulators and alterations in glycemia. The mechanisms underlying such relationships remain uncertain and are the subject of much research, not least because they may reveal new drug targets for diabetes or help in the mitigation of dysglycemia risks with specific therapies. In this issue of Diabetes , Fall et al. (7 …