Effects of Changes in Potassium With Valsartan Use on Diabetes Risk: Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) Trial

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 160 mg 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.