Carbohydrate metabolism during treatment with chlorthalidone and ethacrynic acid.

Abstract

Wilkins (1959), Finnerty (1959), and Freis (1959) were the first to report that treatment with thiazide preparations may affect the carbohydrate metabolism, and perhaps also provoke diabetes mellitus in patients who had not previously suffered from this disorder. In consideration of the widespread use of modern diuretics it is of importance to know how often such a diabetogenic effect may occur.Chlorthalidone (Hygroton) has proved to be suitable for use in the treatment of hypertension and oedema. However, there have been reports of the occurrence of diabetes mellitus, even of fatal cases, when this compound has been used (Moret, 1965).The effect of ethacrynic acid (Edecrin) on carbohydrate metabolism during long-term therapy has not previously been fully investigated. Because of the extent to which this diuretic is now used it would seem that a closer investigation of this problem should be made.In order to assess the effect of the two drugs on carbohydrate metabolism patients with hypertension were investigated, before and after treatment with these preparations, by means of a number of tests for estimating such metabolism.Material and Methods The effect of ethacrynic acid on carbohydrate metabolism was investigated in 15 patients (9 women and 6 men), while that of chlorthalidone was investigated in 16 patients (11 women and 5 men). The first three patients (Cases 1-3) were treated first with chlorthalidone and then with ethacrynic acid; the next nine were treated with the diuretics in the reverse order, while the remainder received only one or other of the drugs.All the patients suffered from mild to moderately severe essential hypertension; none had experienced cerebral vascular attacks, cerebral apoplexy, or head injury. Ten were adiposethat is, their weight exceeded the normal by more than 10%. All had normal renal function, as assessed by investigation of the urine for protein, microscopy of urine, serum creatinine level, and creatinine clearance. Three had a familial disposition to diabetes mellitus, but otherwise none showed evidence of endocrine disorders or of diseases of the liver or pancreas.The patients who were treated with chlorthalidone were aged 45 to 70 years, average 59 years. The total dosages ranged from 6.7 to 43 g., with an average of 14.9 g., over courses of treatment lasting between 62 and 288 days, average 114 days. Those who were treated with ethacrynic acid were aged from 45 to 66 years, average 59 years. The total dosage varied from 1.9 to 13.1 g, average 5.8 g., and the duration of treatment ranged from 42 (Hoffman, 1937). The oral glucose tolerance test was carried out with 1 g. of dehydrated glucose per kilogram of body weight, maximum 70 g. It was considered to be normal if the blood sugar concentration was less than 130 mg./100 ml. two hours after administration of the glucose (limits given by Andersen and Friis, 1967 Friis, 1967).

Drug Treatment of Hypertension in Patients With Diabetes Mellitus

“…Less information is available on loop diuretics and their effects on glucose homeostasis. In nondiabetic subjects, ethacrynic acid induced hyperglycemia but less frequently than chlorthalidone (217). Similarly, in nondiabetic volunteers, neither furosemide nor bumetanide altered glycemic or insulin excursion during an OGTT (196).…”

A comparison of the effects of bumetanide (Burinex) and frusemide on carbohydrate metabolism in the elderly

“…This patient received concomitant treatment with propanolol which itself has been implicated as a precipitating factor 12 . Bumetanide seems to be relatively free from the adverse effect on carbohydrate metabolism 13 , 14 seen with thiazides 2 , frusemide 3 and ethacrynic acid 4 .…”

“…The diabetogenic effect of thiazide diuretics is well established 1 , 2 and has also been described with loop diuretics 3 , 4 . The combination of a diabetogenic effect, together with a potent diuretic response, is potentially dangerous, with the risk of precipitating hyperosmolar diabetic coma.…”

Thiazides and hypokalaemia in diabetic ketoacidosis

“…However, studies in latent or mild diabetics clearly show deleterious effects of chlorothiazide on carbohydrate metabolism (Bojanowicz & Zubowski, 1967). It has been suggested that chlorthalidone and frusemide cause only mild potassium depletion with little or no effect upon glucose intolerance or insulin secretion (Healy et al, 1970) although diabetes mellitus has been reported after chlorthalidone therapy (Andersen & Persson, 1968;Moret, 1965).…”