Role of angiotensin-converting enzyme inhibition in glucose metabolism andrenal injury in diabetes

The role of angiotensin-converting enzyme (ACE) inhibition in glucose metab olism and renal injury in diabetes has been extensively investigated in dia betic humans, as well as in animal models of diabetes. Accumulated data ind icate that ACE inhibitors have either no adverse effect on glucose control or insulin sensitivity or may even improve them. ACE inhibitors also appear to have neutral or positive effects on lipid metabolism. The variability o f results between studies may relate to differences in experimental design, the degree of glycemia or insulin resistance, potassium balance, and dose or duration of ACE inhibitor treatment, among others. In contrast, ACE inhi bitors have proved effective in limiting proteinuria and retarding renal fu nction loss in insulin-dependent diabetes mellitus (IDDM) or non-insulin-de pendent diabetes mellitus (NIDDM) patients. In rats with experimental or sp ontaneous diabetes, ACE inhibitors also reduce proteinuria and limit glomer ular as well as tubulointerstitial damage, independent of their effects on systemic arterial pressure. How ACE inhibitors limit renal injury in diabet es is not entirely clear, but hemodynamic and nonhemodynamic mechanisms may be involved. Increasing evidence suggests that the intrarenal renin-angiot ensin system (RAS) may be altered or activated in the diabetic kidney. Such activation may be specifically inhibited by ACE inhibitors and may explain the superiority of this class of agents over other antihypertensive agents in reducing proteinuria and slowing the progression of diabetic nephropath y. Copyright (C) 1998 by W.B. Saunders Company.