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Longitudinal Association of Statin Treatment With Insulin Sensitivity and Beta-Cell Function in the PROMISE Cohort
Kira Zhi Hua Lai1, Stewart B Harris2, Ravi Retnakaran3,4,5
1Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto M5S 1A8, Canada.
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.
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