title: Role of diuretics, β blockers, and statins in increasing the risk of diabetes in patients with impaired glucose tolerance: reanalysis of data from the NAVIGATOR study.
abstract: OBJECTIVE
  To examine the degree to which use of β blockers, statins, and diuretics in patients with impaired glucose tolerance and other cardiovascular risk factors is associated with new onset diabetes.
  
  
  METHODS
  Reanalysis of data from the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial.
  
  
  METHODS
  NAVIGATOR trial.
  
  
  METHODS
  Patients who at baseline (enrolment) were treatment naïve to β blockers (n=5640), diuretics (n=6346), statins (n=6146), and calcium channel blockers (n=6294). Use of calcium channel blocker was used as a metabolically neutral control.
  
  
  METHODS
  Development of new onset diabetes diagnosed by standard plasma glucose level in all participants and confirmed with glucose tolerance testing within 12 weeks after the increased glucose value was recorded. The relation between each treatment and new onset diabetes was evaluated using marginal structural models for causal inference, to account for time dependent confounding in treatment assignment.
  
  
  RESULTS
  During the median five years of follow-up, β blockers were started in 915 (16.2%) patients, diuretics in 1316 (20.7%), statins in 1353 (22.0%), and calcium channel blockers in 1171 (18.6%). After adjusting for baseline characteristics and time varying confounders, diuretics and statins were both associated with an increased risk of new onset diabetes (hazard ratio 1.23, 95% confidence interval 1.06 to 1.44, and 1.32, 1.14 to 1.48, respectively), whereas β blockers and calcium channel blockers were not associated with new onset diabetes (1.10, 0.92 to 1.31, and 0.95, 0.79 to 1.13, respectively).
  
  
  CONCLUSIONS
  Among people with impaired glucose tolerance and other cardiovascular risk factors and with serial glucose measurements, diuretics and statins were associated with an increased risk of new onset diabetes, whereas the effect of β blockers was non-significant.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00097786.
authors: Duke Clinical Research Institute, Durham, NC, USA.
authors: Lan
authors: L
authors: Shen
authors: Bimal R
authors: BR
authors: Shah
authors: Eric M
authors: EM
authors: Reyes
authors: Laine
authors: L
authors: Thomas
authors: Daniel
authors: D
authors: Wojdyla
authors: Peter
authors: P
authors: Diem
authors: Lawrence A
authors: LA
authors: Leiter
authors: Bernard
authors: B
authors: Charbonnel
authors: Viacheslav
authors: V
authors: Mareev
authors: Edward S
authors: ES
authors: Horton
authors: Steven M
authors: SM
authors: Haffner
authors: Vladimir
authors: V
authors: Soska
authors: Rury
authors: R
authors: Holman
authors: M Angelyn
authors: MA
authors: Bethel
authors: Frank
authors: F
authors: Schaper
authors: Jie-Lena
authors: JL
authors: Sun
authors: John J V
authors: JJ
authors: McMurray
authors: Robert M
authors: RM
authors: Califf
authors: Henry
authors: H
authors: Krum
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000009:adverse effects* / Q000627:therapeutic use; D000368:Aged; D002121:Calcium Channel Blockers / Q000009:adverse effects* / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control; D003510:Cyclohexanes / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology; D004232:Diuretics / Q000009:adverse effects* / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D018149:Glucose Intolerance / Q000150:complications* / Q000188:drug therapy; D005951:Glucose Tolerance Test; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D015994:Incidence; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D000077715:Nateglinide; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000627:therapeutic use; D012307:Risk Factors; D013777:Tetrazoles / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome; D014633:Valine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D000068756:Valsartan
chemical_list: D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers; D003510:Cyclohexanes; D004232:Diuretics; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D013777:Tetrazoles; D000077715:Nateglinide; D010649:Phenylalanine; D000068756:Valsartan; D014633:Valine