Diabetes, impaired glucose tolerance and insulin resistance with diuretics.

There is a definite relation of diuretic treatment to impaired glucose tolerance and biochemical diabetes, and a probable relation to insulin resistance. The effect of diuretics on glucose tolerance is dose-related. Spironolactone does not impair glucose tolerance even at high dosage, but apparent differences between other diuretics may well be due to comparison at doses which are not equivalent. Diuretic-induced changes in carbohydrate metabolism are not conclusively related to altered potassium homeostasis, and impaired glucose tolerance occurs when relatively low doses of thiazide are combined with potassium-sparing agents. The effect of diuretics on glucose tolerance is largely and possibly wholly reversible. These disturbances of carbohydrate homeostasis have been detected by detailed biochemical testing, and their clinical importance is uncertain. In established diabetes, diuretics have a rapid and substantial adverse effect on metabolic control. In non-diabetic subjects diuretics may rarely cause or trigger a serious hyperosmolar non-ketotic diabetic syndrome. This apart, it is not known whether the metabolic changes cause clinical diabetes or lead to microvascular complications in the long-term. It is now established that biochemical diabetes, glucose intolerance and insulin resistance probably do not increase the risk of coronary heart disease in treated hypertensive patients. Diuretics should be avoided in patients with diabetes, otherwise they remain an excellent choice for first-line antihypertensive therapy.