Diabetic vascular injury and ACE. Potential for pharmacological prevention of complications of later life.

Experimental studies have indicated that angiotensin converting enzyme (ACE) inhibitors have multiple actions on the kidney and blood vessels which include both haemodynamic and antitrophic effects. Inhibition of angiotensin II and potentiation of bradykinin have both been postulated to be major mechanisms in mediating the effects of ACE inhibitors. Clinical studies have indicated that these agents postpone end-stage renal failure in macroproteinuric patients with insulin-dependent diabetes mellitus (IDDM). Indeed, these drugs are useful in both hypertensive and normotensive diabetic patients with macroproteinuria. In IDDM patients with microalbuminuria, ACE inhibitors have been shown to decrease albuminuria and to retard the development of overt renal disease. The role of these agents in patients with non-insulin-dependent diabetes mellitus (NIDDM) and early or overt renal disease remains to be clearly delineated. However, preliminary studies suggest a similar beneficial renoprotective effect of ACE inhibitors in NIDDM. It should be appreciated that the presence of micro- or macroproteinuria in NIDDM is a predictor of cardiovascular rather than renal morbidity and mortality. The possibility of cardiovascular protection, in addition to renal protection, being conferred by these drugs needs to be considered in both IDDM and NIDDM, although this issue has not been evaluated in detail.