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

2. Backgrounds Thiazide diuretics are recommended as a 1 st 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

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.