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 (insulin sensitivity index, homeostatic model assessment for insulin sensitivity) and beta-cell function (insulinogenic index/homeostatic model assessment for insulin resistance, insulin secretion sensitivity index-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 (aged 50 years, 74% female) received a statin, predominantly rosuvastatin and atorvastatin. Compared to those with no statin treatment, statin users had lower insulin sensitivity (5.32%-6.36%) and beta-cell function (4.93%-7.59%) (P < .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 female participants, statins reduced insulin sensitivity and beta-cell function, while in male participants 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.