Hypokalemia, glucose intolerance, and hyperinsulinemia during diuretic therapy

Hypokalemia and glucose intolerance may result from diuretic therapy. Increases in plasma insulin and glucose levels have been observed in thiazide-treated hypertensive patients and have been attributed to a diminished insulin sensitivity induced by diuretic therapy. To investigate the effects of hypokalemia on glucose tolerance and insulin secretion, we studied 21 essential and nine diabetic hypertensive patients after 4 weeks of placebo and after 4 weeks of chlorthalidone therapy (25 mg/day). Plasma glucose and insulin levels were measured for a 3-hour period after a 75-g glucose oral dose. Hypokalemia developed in seven of the essential hypertensive patients (HK group), whereas only one diabetic patient had decreased plasma potassium levels to below 3.5 meq/l. The results obtained in the HK group after chlorthalidone showed that plasma glucose and insulin values increased after the oral glucose load to levels significantly higher than those observed after placebo. In contrast, the patient who remained normokalemic after chlorthalidone did not show any change in plasma insulin and glucose levels during glucose tolerance testing. These results show that diuretic therapy may induce hyperglycemia and hyperinsulinemia and suggest that potassium depletion is involved in the increase in insulin resistance that has been demonstrated during thiazide therapy.