Statin therapy associated with increased insulin resistance and type two diabetes

According to a new study, statin therapy may increase the risk of type 2 diabetes by decreasing insulin sensitivity and secretion. Overall, there was a 46% increase in the risk of type two diabetes.

Statins are considered to be safe and well-tolerated medications commonly used for the prevention of cardiovascular disease (CVD) events in individuals with and without diabetes. However, recent studies showed that statins might increase the risk of type 2 diabetes. The goals of this study were to analyze the effects of statins on the risk of type 2 diabetes and investigate the mechanisms of this process based on insulin resistance and insulin secretion.

This study was a 6-year follow-up of the population-based Metabolic Syndrome in Men (METSIM) performed in 2005 to 2010. A total of 8,749 non-diabetic men aged 45 to 73 years old was randomly selected from a population in Kuopoi, Eastern Finland. An OGTT (75 g of glucose, glucose and insulin measurements at 0, 30, and 120 min) was performed, then glucose tolerance was classified based on the American Diabetes Association criteria. Exclusion criteria included patients with previously diagnosed type 1 diabetes, newly or previously diagnosed type 2 diabetes, or those without an OGTT at baseline. A total of 625 of the 8,749 individuals enrolled were diagnosed with type 2 diabetes during a 5.9 year follow-up study. Out of 8,749 individuals, 2,142 patients were on statin medication at baseline. Measured variables included height, weight, BMI, waist circumference, smoking status, family history of diabetes, physical activity, alcohol intake, the use of beta-blockers and diuretics at baseline, and history of non-fatal myocardial infarction or stroke. Laboratory measurements included plasma glucose, HbA1c, plasma insulin concentrations, LDL, HDL, and total triacylglycerols. T-test and chi-squared tests were used for statistical analyses.

The results showed that individuals on statin treatment had a 46% increased risk of type 2 diabetes (adjusted HR 1.46 [95% CI 1.22, 1.74]). The increased risk is dose-dependent for atorvastatin and simvastatin (simvastatin HR 1.44 [95% CI 1.23, 1.68] and 1.28 [95% CI 1.01, 1.62] for high and low dose, respectively, and atorvastatin HR 1.37 [95% CI 1.14, 1.65]). Study also showed that statin treatment increased glucose AUC, 2 h glucose (2hPG), and fasting plasma glucose at follow-up. Insulin sensitivity and insulin secretion were decreased by 24% and 12%, respectively, in statin group compared to non-statin group (p<0.01). The decrease in insulin sensitivity and insulin secretion were dose dependent for atorvastatin and simvastatin.

In conclusion, after adjustment for confounding factors, statin treatment was shown to increase the risk of type 2 diabetes due to decreases in insulin sensitivity and insulin secretion.

Practice Pearls:
•Statin therapy was associated with a 46% increase in the risk of type 2 diabetes.
•Insulin sensitivity and insulin secretion were decreased by 24% and 12%, respectively in statin group compared to non-statin group.
•For atorvastatin and simvastatin, the risk of type 2 diabetes and the decreased in insulin sensitivity and insulin secretion were dose-dependent.

Cederberg et al. “Increased risk of diabetes with statin treatment is associated with impaired insulin sensitivity and insulin secretion: a 6 year follow-up study of the METSIM cohort.” Diabetologia. May 2015;58(5):1109-1117.

From Diabetes in Control 24 April 2015