title: Effects of changes in potassium with valsartan use on diabetes risk: Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial.
abstract: BACKGROUND
  Low and low-normal serum potassium is associated with an increased risk of diabetes. We hypothesized that the protective effect of valsartan on diabetes risk could be mediated by its effect of raising serum potassium.
  
  
  METHODS
  We analyzed data from the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial, which randomized participants at risk for diabetes to either valsartan (up to 160mg daily) or no valsartan. Using Cox models, we evaluated the effect of valsartan on diabetes risk over a median of 4 years of follow-up and calculated the mediation effect of serum potassium as the difference in treatment hazard ratios from models excluding and including 1-year change in serum potassium. The 95% confidence interval (CI) for the difference in log hazard ratios was computed by bootstrapping.
  
  
  RESULTS
  The hazard ratio for developing diabetes among those on valsartan vs. no valsartan was 0.866 (95% CI = 0.795-0.943) vs. 0.868 (95% CI = 0.797-0.945), after controlling for 1-year change in potassium. The bootstrap 95% CI for a difference in these log hazard ratios was not statistically significant (-0.003 to 0.009).
  
  
  CONCLUSIONS
  Serum potassium does not appear to significantly mediate the protective effect of valsartan on diabetes risk.
authors: Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA. ranee.chatterjee@duke.edu
authors: Ranee
authors: R
authors: Chatterjee
authors: Laine
authors: L
authors: Thomas
authors: Laura
authors: L
authors: Svetkey
authors: Frederick L
authors: FL
authors: Brancati
authors: Robert M
authors: RM
authors: Califf
authors: David
authors: D
authors: Edelman
mesh_terms: D000959:Antihypertensive Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D003510:Cyclohexanes / Q000627:therapeutic use*; D003920:Diabetes Mellitus / Q000097:blood / Q000209:etiology*; D005260:Female; D005500:Follow-Up Studies; D018149:Glucose Intolerance / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D000077715:Nateglinide; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011188:Potassium / Q000097:blood*; D013777:Tetrazoles / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D014633:Valine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000068756:Valsartan
chemical_list: D000959:Antihypertensive Agents; D015415:Biomarkers; D003510:Cyclohexanes; D007004:Hypoglycemic Agents; D013777:Tetrazoles; D000077715:Nateglinide; D010649:Phenylalanine; D000068756:Valsartan; D014633:Valine; D011188:Potassium
keywords: blood pressure; diabetes; hypertension; risk; serum potassium; valsartan.