Article

Diabetologia

, Volume 58, Issue 5, pp 1109-1117

First online:

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

  • Henna CederbergAffiliated withInstitute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital
  • , Alena StančákováAffiliated withInstitute of Clinical Medicine, Internal Medicine, University of Eastern Finland
  • , Nagendra YaluriAffiliated withInstitute of Clinical Medicine, Internal Medicine, University of Eastern Finland
  • , Shalem ModiAffiliated withInstitute of Clinical Medicine, Internal Medicine, University of Eastern Finland
  • , Johanna KuusistoAffiliated withInstitute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital
  • , Markku LaaksoAffiliated withInstitute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital Email author 

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 ≥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 <5.0 mmol/l) compared with individuals without statin treatment (p < 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.

Keywords

2-h glucose Fasting glucose HbA1c Insulin resistance Insulin sensitivity Statin Type 2 diabetes