BMI mediates effects of statins on diabetes risk

Higher body mass index (BMI) plays a significant role in more than half of the diabetogenic effects of statins, reports a study. These effects, however, do not extend to other commonly used lipid modifiers.

The research team used established genetic variants to mimic commonly used lipid modifiers, such as statins, PCSK9 inhibitors, and ezetimibe. They then examined the effects of these lipid modifiers on type 2 diabetes, glycated haemoglobin (HbA1c), fasting insulin, fasting glucose, and BMI in the largest relevant genome-wide association studies (GWAS) in people of European ancestry and in some East Asians.

Finally, multivariable Mendelian randomization was used to determine the role of lipid modifiers, independent of BMI.

Genetically mimicked effects of statins and ezetimibe, but not PCSK9 inhibitors, significantly correlated with increased type 2 diabetes risk (statin: odds ratio [OR], 1.74, 95 percent confidence interval [CI], 1.49‒2.03; ezetimibe: OR, 1.92, 95 percent CI, 1.22‒3.02; PCSK9 inhibitors: OR, 1.06, 95 percent CI, 0.87‒1.29 per SD reduction in low-density lipoprotein [LDL] cholesterol).

Notably, only the genetic mimics of statins showed a significant association with higher BMI (0.33 per SD reduction in LDL cholesterol). This accounted for 54 percent of the total effect of statins on the risk of type 2 diabetes.

“Further investigations are needed to clarify drug-specific mechanisms underlying the effects of lipid modifiers on type 2 diabetes,” the researchers said.