Mechanisms of diuretic effects on carbohydrate tolerance, insulin sensitivity and lipid levels.

Diuretics have long been recognized to increase the concentration of some atherogenic plasma lipids and to reduce insulin sensitivity and adversely influence carbohydrate tolerance, but the mechanisms responsible have not been conclusively established. Early studies reporting diabetes in diuretic-treated patients implicated potassium loss as responsible. More recent observations have extended this suggestion by also demonstrating a role for the renin-angiotensin-aldosterone system. In addition, direct effects of antihypertensive agents on insulin sensitivity have been demonstrated; both hormonal and haemodynamic factors have been implicated. Diuretic-induced lipid changes have also been consistently observed, but the mechanisms for these findings are much less clear. A link between the carbohydrate and insulin alterations and those of lipids has been suggested. Plasma catecholamine concentration may also be increased by diuretics and it is possible that this may also influence lipid metabolism. While the mechanisms of these metabolic effects of diuretics are not yet clearly established, useful clues based on dose relationships and susceptible populations can be discerned. Observations from combination drug therapies also provide additional information regarding potential mechanisms. The availability of new drug therapies associated with few metabolic changes further suggest that effective diuretic therapy need not always be associated with significant adverse metabolic changes.