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(Hypertension. 2008;52:1012.)
© 2008 American Heart Association, Inc.

Editorial Commentaries

Hypertension, Hypokalemia, and Thiazide-Induced Diabetes

A 3-Way Connection

Rajiv Agarwal

From the Division of Nephrology, Department of Medicine, Indiana University School of Medicine; and the Richard L. Roudebush Veterans’ Affairs Medical Center, Indianapolis, Ind.

Correspondence to Rajiv Agarwal, Veterans’ Affairs Medical Center, 111N, 1481 W 10th St, Indianapolis, IN 46202. E-mail ragarwal@iupui.edu

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Reduction in the dose of diuretics to treat essential hypertension occurred with the recognition that higher doses of thiazides cause hypokalemia, glucose intolerance, and hyperuricemia but little additional reduction in blood pressure.¹ Subsequently, large randomized, controlled trials have demonstrated a higher incidence of diabetes mellitus with thiazide diuretics compared with other antihypertensive drugs.² A meta-analysis done with 143153 participants without diabetes mellitus in 22 clinical trials showed that thiazide diuretics and β-blockers had similarly high risks of developing new-onset diabetes mellitus, followed by placebo and calcium channel blockers; the most protective were angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors.³ This detrimental effect on glucose tolerance together with the growing epidemic of diabetes and obesity has reined in the wider use of thiazides despite being effective and inexpensive antihypertensive drugs with strong cardiovascular benefits.

Whether thiazide-induced diabetes mellitus has the same adverse prognostic significance as spontaneously occurring diabetes mellitus is not known with certainty.² If thiazide diuretics unmask the presence of underlying diabetes mellitus, then the earlier detection of diabetes with more aggressive hypertension, lipid, and metabolic control may in fact, instead of being harmful, be protective. There is also some evidence that, although new-onset diabetes mellitus is associated with cardiovascular mortality, treatment of such patients with diuretics has survival benefits. In a long-term analysis of the Systolic Hypertension in Elderly Program with a mean follow-up of 14.3 years, the long-term fatality rate was higher in those with had diabetes mellitus at baseline, followed by patients who developed diabetes during . . . [Full Text of this Article]

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