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Thiazide diuretics, Potassium, and the Development of Diabetes

Thiazide diuretics, Potassium, and the Development of Diabetes. A Quantitative Review Hypertension2006_219. Backgrounds.

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Thiazide diuretics, Potassium, and the Development of Diabetes

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  1. Thiazide diuretics, Potassium, and the Development of Diabetes A Quantitative Review Hypertension2006_219

  2. Backgrounds • Thiazide diuretics are recommended as a 1st choice for HTN by current national clinical practice guidelines and results from the ALLHAT*. *Antyhypertensive and Lipid Lowering treatment to prevent Heart Attack Trial • But 4-year incidence of new-onset diabetes was significantly higher in thiazide group(11.6%) than either in Ca channel blocker group(9.8%) or ARB group(8.1%). (P<0.05)

  3. By the way---ALLHAT---(1) • Antihypertensive and Lipid Lowering treatment to prevent Heart Attack Trial • Consists of antihypertensive therapy and lipid lowering treatment

  4. By the way---ALLHAT---(2)

  5. By the way---ALLHAT---(3) potassium value was significantly dropped in the thiazide group

  6. By the way---ALLHAT---(4) Blood glucose in thiazide group was significantly elevated.

  7. This study • Provides a review of intervention studies that included data on the relation between thiazide-induced hypokalemia and glucose intolerance • Aimes to evaluate clinical trials • that used thiazide diuretics • that reported metabolic effects on potassium and glucose

  8. Methods • 3 medical literature sourse • The Abridged Index Medicus 1966.1-2004.6 • Cochrane Controlled Trial Database • Journal of Hypertension, Journal of Human Hypertension, Hypertension, American Journal of Hypertension, Journal of Clinical Hypertension and Blood Pressure • Search terms: “diuretics, thiazide”, “hydrochlorothiazide”, or “chlorthalidone”

  9. Methods • Limited to adult, human, subject published in English using the terms “controlled clinical trial” or “randomized controlled trial” • Inclusion criteria of the study • Trials that mentioned Pts with HTN ≧8wks and study arms with Pt≧10 • Trials that use thiazide-type diuretics as a single agent or as a primary initial therapy • Trials that mesures both potassium and glucose • Exclusion criteria of the study • Trials that used combinations of antihypertensive agents • Trials that did not attempt to separate results by the type of diuretic or drug

  10. Methods • collected data are; • Trial design, size, duration • Type of thiazide drug, initial dose, dose titrationregimen, use of potassium supplements or potassium sparing agents • Metabolic effects on potassium and glucose

  11. Data Analyses • Key data: Average change in potassium and glucose • calcurated as; • Difference in final value in thiazide group and that in placebo group (placebo comparator trials) • Difference in final value and baseline value (baseline comparator trials; no placebo group)

  12. Data Analyses • An unweighed Pearson correlation, the nonparametric Spearman correlation, Pearson correlation weighed according to sample size • 2 additional subanalyses • Trials using >50mg of hydrochlorothiazide were excluded • Trials using any potassium supplements and/or potassium sparing agents are compared

  13. Results Figure 1.

  14. Results

  15. Results

  16. Results

  17. Results

  18. Discussion • This review revealed a significant inverse relationship between K and glucose ; lower K associated with higher glucose • Many other recent clinical trials support this data • In one study, the highest fasting blood glucose occurred woth potassium concentrations <3.9mmol/L • But results from this study must be used carefully because this study has some limitations (; varied study design, Pt type, way of comparison…..). • Test for causality for the effect of thiazide-induced hypokalemia on glucose intolerance must come from a rondomized trial

  19. Perspectives • This study suggests that treatment of thiazide-induced hypokalemia could lessen glucose intolirance and possibly the development of diabetes

  20. Perspectives • As discussed above, it seemes reasonable to target K ≧4mmol/L among all Pts taking thiazide. • It can be acomplished by using potassium-sparing diuretics and/or oral potassium supplementation. It seems good to add ACEi or ARB to thiazide because many Pts are taking 2 or more antihypertensive agents as well as because it is showen that this combination can prevent hypokalemia.

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