title: Predictors for glucose change in hypertensive participants following short-term treatment with atenolol or hydrochlorothiazide.
abstract: OBJECTIVE
  To develop and validate a predictive model for glucose change and risk for new-onset impaired fasting glucose in hypertensive participants following treatment with atenolol or hydrochlorothiazide (HCTZ).
  
  
  METHODS
  Randomized multicenter clinical trial.
  
  
  METHODS
  A total of 735 white or African-American men and women with uncomplicated hypertension.
  
  
  RESULTS
  Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) is a randomized clinical trial to assess the genetic and nongenetic predictors of blood pressure response and adverse metabolic effects following treatment with atenolol or HCTZ. To develop and validate predictive models for glucose change, PEAR participants were randomly divided into a derivation cohort of 367 and a validation cohort of 368. Linear and logistic regression modeling were used to build models of drug-associated glucose change and impaired fasting glucose (IFG), respectively, in the derivation cohorts. These models were then evaluated in the validation cohorts. For glucose change after atenolol or HCTZ treatment, baseline glucose was a significant (p<0.0001) predictor, explaining 13% of the variability in glucose change after atenolol and 12% of the variability in glucose change after HCTZ. Baseline glucose was also the strongest and most consistent predictor (p<0.0001) for development of IFG after atenolol or HCTZ monotherapy. The area under the receiver operating curve was 0.77 for IFG after atenolol and 0.71 after HCTZ treatment, respectively.
  
  
  CONCLUSIONS
  Baseline glucose is the primary predictor of atenolol or HCTZ-associated glucose increase and development of IFG after treatment with either drug.
authors.affiliation: Department of Pharmacotherapy and Translational Research, Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, Florida.
authors.forename: Mariellen J
authors.initials: MJ
authors.lastname: Moore
authors.forename: Yan
authors.initials: Y
authors.lastname: Gong
authors.forename: Wei
authors.initials: W
authors.lastname: Hou
authors.forename: Karen
authors.initials: K
authors.lastname: Hall
authors.forename: Siegfried O F
authors.initials: SO
authors.lastname: Schmidt
authors.forename: Robert Whitney
authors.initials: RW
authors.lastname: Curry
authors.forename: Amber L
authors.initials: AL
authors.lastname: Beitelshees
authors.forename: Arlene
authors.initials: A
authors.lastname: Chapman
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Turner
authors.forename: Gary L
authors.initials: GL
authors.lastname: Schwartz
authors.forename: Kent
authors.initials: K
authors.lastname: Bailey
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
authors.forename: John G
authors.initials: JG
authors.lastname: Gums
authors.forename: Rhonda M
authors.initials: RM
authors.lastname: Cooper-DeHoff
authors.forename: Julie A
authors.initials: JA
authors.lastname: Johnson
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000009:adverse effects* / Q000627:therapeutic use; D000328:Adult; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use; D001262:Atenolol / Q000009:adverse effects* / Q000627:therapeutic use; D001786:Blood Glucose / Q000032:analysis; D015331:Cohort Studies; D004232:Diuretics / Q000009:adverse effects* / Q000627:therapeutic use; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D018149:Glucose Intolerance / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D006852:Hydrochlorothiazide / Q000009:adverse effects* / Q000627:therapeutic use; D006943:Hyperglycemia / Q000139:chemically induced* / Q000453:epidemiology; D006973:Hypertension / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D012372:ROC Curve; D012306:Risk; D014481:United States / Q000453:epidemiology
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D000959:Antihypertensive Agents; D001786:Blood Glucose; D004232:Diuretics; D006852:Hydrochlorothiazide; D001262:Atenolol
keywords: atenolol; hydrochlorothiazide; hyperglycemia; impaired fasting glucose; thiazide diuretics; β-Blockers