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Thiazide Diuretics Exacerbate Fructose-Induced Metabolic Syndrome

Sirirat Reungjui^*, Carlos A. Roncal^*, Wei Mu^*, Titte R. Srinivas^*, Dhavee Sirivongs, Richard J. Johnson^* and Takahiko Nakagawa^*

^* Division of Nephrology, Hypertension and Transplantation, University of Florida, Gainesville, Florida; and Division of Nephrology, Khon Kaen University, Khon Kaen, Thailand

Correspondence: Dr. Sirirat Reungjui, current address is Division of Nephrology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand 40002. Phone: +66-43-363746; Fax: +66-43-347542; E-mail: sirirt_a{at}kku.ac.th

Received for publication April 6, 2007. Accepted for publication June 20, 2007.

Fructose is a commonly used sweetener associated with diets that increase the prevalence of metabolic syndrome. Thiazide diuretics are frequently used in these patients for treatment of hypertension, but they also exacerbate metabolic syndrome. Rats on high-fructose diets that are given thiazides exhibit potassium depletion and hyperuricemia. Potassium supplementation improves their insulin resistance and hypertension, whereas allopurinol reduces serum levels of uric acid and ameliorates hypertension, hypertriglyceridemia, hyperglycemia, and insulin resistance. Both potassium supplementation and treatment with allopurinol also increase urinary nitric oxide excretion. We suggest that potassium depletion and hyperuricemia in rats exacerbates endothelial dysfunction and lowers the bioavailability of nitric oxide, which blocks insulin activity and causes insulin resistance during thiazide usage. Addition of potassium supplements and allopurinol with thiazides might be helpful in the management of metabolic syndrome.

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Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673