title: 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: OBJECTIVE
  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
  Statin treatment increased the risk of type 2 diabetes by 46%, attributable to decreases in insulin sensitivity and insulin secretion.
authors.affiliation: Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital, P.O. Box 1627, 70211, Kuopio, Finland.
authors.forename: Henna
authors.initials: H
authors.lastname: Cederberg
authors.forename: Alena
authors.initials: A
authors.lastname: Stančáková
authors.forename: Nagendra
authors.initials: N
authors.lastname: Yaluri
authors.forename: Shalem
authors.initials: S
authors.lastname: Modi
authors.forename: Johanna
authors.initials: J
authors.lastname: Kuusisto
authors.forename: Markku
authors.initials: M
authors.lastname: Laakso
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000209:etiology; D005500:Follow-Up Studies; D005951:Glucose Tolerance Test; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000188:drug therapy; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D000078790:Insulin Secretion; D008297:Male; D008875:Middle Aged; D012306:Risk
chemical_list: D001786:Blood Glucose; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007328:Insulin