Genetic Studies Suggest That Diabetes Risk Is Inherent in the Action of Statins

Statin drugs, which lower LDL cholesterol concentrations by inhibiting 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), significantly raise risk for new-onset type 2 diabetes mellitus. But is this diabetogenic effect inherent in inhibition of HMGCR?

Using the technique of “Mendelian randomization,” researchers identified two single-nucleotide polymorphisms (SNPs) within or near the gene that encodes HMGCR; each SNP has one allele that is associated strongly with low serum LDL cholesterol levels and can be regarded as a proxy for HMGCR inhibition. Data from 43 observational genetic studies (>220,000 patients) showed that, for both SNPs, the alleles associated with low LDL cholesterol levels also were associated with excess incidence and prev…