Changes in Serum Potassium Mediate Thiazide-Induced Diabetes

  • Tariq Shafi
    From the Department of Medicine, Division of Nephrology (T.S., R.S.P.), and General Internal Medicine (L.J.A., E.R.M., M.J.K.), Department of Pediatrics, Division of Nephrology (R.S.P.), Johns Hopkins University School of Medicine; Department of Epidemiology (L.J.A., E.R.M., M.J.K., R.S.P.), Johns Hopkins Bloomberg School of Public Health; and the Welch Center for Prevention, Epidemiology and Clinical Research (L.J.A., E.R.M., M.J.K., R.S.P.), Baltimore, Md.
  • Lawrence J. Appel
    From the Department of Medicine, Division of Nephrology (T.S., R.S.P.), and General Internal Medicine (L.J.A., E.R.M., M.J.K.), Department of Pediatrics, Division of Nephrology (R.S.P.), Johns Hopkins University School of Medicine; Department of Epidemiology (L.J.A., E.R.M., M.J.K., R.S.P.), Johns Hopkins Bloomberg School of Public Health; and the Welch Center for Prevention, Epidemiology and Clinical Research (L.J.A., E.R.M., M.J.K., R.S.P.), Baltimore, Md.
  • Edgar R. Miller
    From the Department of Medicine, Division of Nephrology (T.S., R.S.P.), and General Internal Medicine (L.J.A., E.R.M., M.J.K.), Department of Pediatrics, Division of Nephrology (R.S.P.), Johns Hopkins University School of Medicine; Department of Epidemiology (L.J.A., E.R.M., M.J.K., R.S.P.), Johns Hopkins Bloomberg School of Public Health; and the Welch Center for Prevention, Epidemiology and Clinical Research (L.J.A., E.R.M., M.J.K., R.S.P.), Baltimore, Md.
  • Michael J. Klag
    From the Department of Medicine, Division of Nephrology (T.S., R.S.P.), and General Internal Medicine (L.J.A., E.R.M., M.J.K.), Department of Pediatrics, Division of Nephrology (R.S.P.), Johns Hopkins University School of Medicine; Department of Epidemiology (L.J.A., E.R.M., M.J.K., R.S.P.), Johns Hopkins Bloomberg School of Public Health; and the Welch Center for Prevention, Epidemiology and Clinical Research (L.J.A., E.R.M., M.J.K., R.S.P.), Baltimore, Md.
  • Rulan S. Parekh
    From the Department of Medicine, Division of Nephrology (T.S., R.S.P.), and General Internal Medicine (L.J.A., E.R.M., M.J.K.), Department of Pediatrics, Division of Nephrology (R.S.P.), Johns Hopkins University School of Medicine; Department of Epidemiology (L.J.A., E.R.M., M.J.K., R.S.P.), Johns Hopkins Bloomberg School of Public Health; and the Welch Center for Prevention, Epidemiology and Clinical Research (L.J.A., E.R.M., M.J.K., R.S.P.), Baltimore, Md.

抄録

<jats:p> Thiazides, recommended as first-line antihypertensive therapy, are associated with an increased risk of diabetes. Thiazides also lower serum potassium. To determine whether thiazide-induced diabetes is mediated by changes in potassium, we analyzed data from 3790 nondiabetic participants in the Systolic Hypertension in Elderly Program, a randomized clinical trial of isolated systolic hypertension in individuals aged ≥60 years treated with chlorthalidone or placebo. Incident diabetes was defined by self-report, antidiabetic medication use, fasting glucose ≥126 mg/dL, or random glucose ≥200 mg/dL. The mediating variable was change in serum potassium during year 1. Of the 459 incident cases of diabetes during follow-up, 42% occurred during year 1. In year 1, the unadjusted incidence rates of diabetes per 100 person-years were 6.1 and 3.0 in the chlorthalidone and placebo groups, respectively. In year 1, the adjusted diabetes risk (hazard ratio) with chlorthalidone was 2.07 (95% CI: 1.51 to 2.83; <jats:italic>P</jats:italic> <0.001). After adjustment for change in serum potassium, the risk was significantly reduced (hazard ratio: 1.54; 95% CI: 1.09 to 2.17; <jats:italic>P</jats:italic> =0.01); the extent of risk attenuation (41%; 95% CI: 34% to 49%) was consistent with a mediating effect. Each 0.5-mEq/L decrease in serum potassium was independently associated with a 45% higher adjusted diabetes risk (95% CI: 24% to 70%; <jats:italic>P</jats:italic> <0.001). After year 1, chlorthalidone use was not associated with increased diabetes risk. In conclusion, thiazide-induced diabetes occurs early after initiating treatment and appears to be mediated by changes in serum potassium. Potassium supplementation might prevent thiazide-induced diabetes. This hypothesis can and should be tested in a randomized trial. </jats:p>

収録刊行物

  • Hypertension

    Hypertension 52 (6), 1022-1029, 2008-12

    Ovid Technologies (Wolters Kluwer Health)

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