Statins and type 2 diabetes: genetic studies on target

Abstract

The topic of the side-effects of statin treatment is important and controversial. In The Lancet, Daniel Swerdlow and colleagues1 used an updated meta-analysis of trials to investigate whether or not statins increased the risk of type 2 diabetes, and a genetic approach to address how statins might increase the risk of the disorder. Using data from 20 randomised controlled trials, they confirm findings from previous reports that statin treatment increased the risk of incident type 2 diabetes, with an odds ratio (OR) of 1·12 (95% CI 1·06–1·18) versus controls. In contrast to previous efforts, they then studied common genetic variants near the gene encoding the HMG-coenzyme A (HMGCoA) reductase protein—the enzyme inhibited by statins to lower LDL cholesterol. Genome-wide association studies had previously identified these variants as associated with altered circulating LDL cholesterol concentrations with robust levels of statistical confidence.2 Using these genetic variants and a combination of their own and published data, the investigators provide evidence that reduced HMGCoA activity causes a slight increased risk of type 2 diabetes (rs17238484-G allele OR per allele 1·02, 95% CI 1·00–1·05; rs12916 allele 1·06, 1·03–1·09), and therefore surmise that an increased risk of type 2 diabetes is at least partly conferred by an on-target effect of statins.