Mechanisms of Statin Therapy–Related Diabetes Mellitus | Journal Scan

Study Questions:

What are the prevalence and mechanisms of “statin-induced” diabetes mellitus?

Methods:

This was a prospective study of initially nondiabetic men participating in the population-based METSIM (Metabolic Syndrome in Men) study. The outcome of interest was development of diabetes, the diagnosis of which was based on the following criteria: 1) fasting plasma glucose, 2-hour plasma glucose in oral glucose tolerance test, or glycated hemoglobin ≥6.5%; 2) the initiation of glucose-lowering medication; or 3) documentation of physician-diagnosed type 2 diabetes. Insulin sensitivity and secretion were determined.

Results:

There were 8,749 nondiabetic participants. Follow-up was 5.9 years, during which period 625 developed type 2 diabetes. Those treated with statins (n = 2,142) developed diabetes more often than did participants without statin treatment (11.2% vs. 5.8%, p < 0.001). In adjusted analyses, the hazard ratio was 1.46 (95% confidence interval, 1.22-1.74). Compared to no statin treatment, simvastatin and atorvastatin increased the risk of type 2 diabetes; other statins did not increase risk. Insulin sensitivity decreased by 24% and insulin secretion by 12% in individuals on statin treatment, compared to those who were not.

Conclusions:

The authors concluded that decreases in insulin sensitivity and insulin were mechanisms through which statin treatment increased risk of diabetes.

Perspective:

This is an important study that examines the risk of developing diabetes mellitus associated with statin treatment. The authors write that statin treatment increased the risk of type 2 diabetes by 46%. This should be interpreted with caution, as this statistic stands in contrast to much lower estimates (e.g., 9% increased risk) in other literature. Furthermore, this increased risk should be framed in the context of the anticipated cardiovascular benefit of statin therapy. Nonetheless, the authors add value by helping elucidate mechanisms of diabetes mellitus associated with statin treatment.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Nonstatins, Novel Agents, Statins, Diet

Keywords: Diabetes Mellitus, Type 2, Glucose Tolerance Test, Fasting, Glucose, Hemoglobin A, Glycosylated, Insulin, Insulin Resistance, Simvastatin, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Metabolic Syndrome X, Primary Prevention, Male, Prospective Studies, Risk


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