Statins are used to lower cholesterol, but they also increase the risk of type II diabetes. Researchers aimed to find out whether this risk is owing to statins’ mechanism of action — the inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR).
They analysed measurements such as weight, waist-to-hip ratio, blood glucose levels and insulin concentrations in people with mutations in the HMGCR gene, which mimics the effect of statins. Data were available for up to 223,463 individuals from 43 genetic studies. Like statins, mutations in the HMGCR gene were associated with an increased risk of type 2 diabetes and weight gain. Inhibition of HMGCR and an increase in weight is at least partly responsible for the type 2 diabetes risk, according to the study authors, writing in The Lancet (online, 24 September 2014).
The researchers also found that high-dose statins are not associated with weight gain compared with low doses, but they do increase the risk of diabetes, suggesting the relationship is complex.