Longitudinal association of statin treatment with insulin sensitivity and beta-cell function in the PROMISE cohort

Context: Statin treatment lowers low-density lipoprotein (LDL) cholesterol thereby reducing cardiovascular risk. Meta-analyses of clinical trials report a higher risk of new-onset type 2 diabetes with statins. Current clinical evidence regarding effects of statins on insulin sensitivity and beta-cell function is limited.

Objective: We examined the effects of statin treatment on longitudinal changes in early risk phenotypes for type 2 diabetes.

Methods: The PROMISE cohort is a longitudinal study of adults at-risk for type 2 diabetes. Data from baseline and 3 follow-up visits over 9 years were used to estimate insulin sensitivity (ISI, HOMA2-%S) and beta-cell function (IGI/IR, ISSI-2). Statin use was self-reported. Associations of statins with changes in metabolic markers were determined through Generalized Estimating Equations.

Results: Over 9 years, 169 of 498 participants (50 years, 74% female) received a statin, predominantly rosuvastatin and atorvastatin. Compared to no statin treatment, statin users had lower insulin sensitivity (5.32-6.36%) and beta-cell function (4.93-7.59%) (p<0.001) adjusting for metabolic risk factors. Rosuvastatin was associated with decreased insulin sensitivity and beta-cell function, while atorvastatin showed moderate inverse association with beta-cell function and insulin sensitivity. In females, statins reduced insulin sensitivity and beta-cell function, while in males only beta-cell function was altered.

Conclusion: Statin treatment was associated with lowered insulin sensitivity and beta-cell function with potential differential effects among statin agents and the sexes.