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

Abstract

Aims/hypothesis:
The aim of this work was to investigate the mechanisms underlying the risk of type 2 diabetes associated with statin treatment in the population-based Metabolic Syndrome in Men (METSIM) cohort.

Methods:
A total of 8,749 non-diabetic participants, aged 45–73 years, were followed up for 5.9 years. New diabetes was diagnosed in 625 men by means of an OGTT, HbA1c greater than or equal to 6.5% (48 mmol/mol) or glucose-lowering medication started during the follow-up. Insulin sensitivity and secretion were evaluated with OGTT-derived indices.

Results:
Participants on statin treatment (N=2,142) had a 46% increased risk of type 2 diabetes (adjusted HR 1.46 [95% CI 1.22, 1.74]). The risk was dose dependent for simvastatin and atorvastatin. Statin treatment significantly increased 2 h glucose (2hPG) and glucose AUC of an OGTT at follow-up, with a nominally significant increase in fasting plasma glucose (FPG). Insulin sensitivity was decreased by 24% and insulin secretion by 12% in individuals on statin treatment (at FPG and 2hPG less than 5.0 mmol/l) compared with individuals without statin treatment ( p less than 0.01). Decreases in insulin sensitivity and insulin secretion were dose dependent for simvastatin and atorvastatin.

Conclusions/interpretation:
Statin treatment increased the risk of type 2 diabetes by 46%, attributable to decreases in insulin sensitivity and insulin secretion.