Reduction of ACE Activity Is Insufficient to Decrease Microalbuminuria in Normotensive Patients With Type 1 Diabetes

Abstract

OBJECTIVE -To study whether administration of 1.25 and 5.0 mg ramipril daily, compared with placebo treatment, reduces the urinary albumin excretion rate (UAER) in normotensive patients with type 1 diabetes.RESEARCH DESIGN AND METHODS -Ramipril was administered double blind at two different doses (1.25 [n ϭ 19] and 5.0 mg [n ϭ 18]), and compared with placebo (n ϭ 18) after a single-blind placebo period of 1-4 weeks. The patients (total, n ϭ 55; women, n ϭ 14) were followed for 2 years. To document an effect on the renin-angiotensin system, ACE activity and plasma-renin activity (PRA) were measured. In addition, 24-h ambulatory blood pressure (BP) was recorded at baseline and repeated after 1 and 2 years using a Spacelab 90207 ambulatory BP recording device (Spacelab, Redmont, CA).RESULTS -Both doses of ramipril were sufficient to reduce ACE activity and to increase PRA significantly as compared with placebo (P Ͻ 0.05 for both). On the other hand, neither ambulatory nor clinic BP was affected by either dose of ramipril compared with the placebo group. There was no progression of UAER in the placebo group during the 2 years of the study. Analysis of covariance showed no differences in UAER between the three treatment groups at year 1 (P ϭ 0.94) or year 2 (P ϭ 0.97), after adjusting for baseline. Furthermore, there were no statistically significant changes from baseline UAER within any of the three treatment groups.CONCLUSIONS -Treatment with ramipril did not affect microalbuminuria or clinic or ambulatory BP in this study. On the basis of the present study, we question the clinical use of ACE inhibitors in stably normotensive patients with type 1 diabetes and microalbuminuria in whom a concomitant reduction in BP is not demonstrated. Diabetes Care 24:919 -924, 2001A CE inhibitors are often prescribed to normotensive patients with type 1 diabetes and microalbuminuria (1). Numerous reports have proved that treatment with ACE inhibitors reduces the urinary albumin excretion rate (UAER) in this particular category of patients (2-16). However, many of these trials were of rather short duration or contained only a small number of patients (2-8). When the effect of ACE inhibitors on UAER has been compared with that of other antihypertensive drugs, a more profound reduction has often been achieved with ACE inhibition (2,7,8,10). Demonstration of a reduction in UAER, even after correction for changes in blood pressure (BP) (17), and two large studies of the short-acting ACE inhibitor captopril (9,11) also implicate that pharmacological inhibition of ACE confers renoprotective effects that are independent of changes in BP in normotensive patients with type 1 diabetes.We aimed to study whether the reduction of UAER in normotensive patients with type 1 diabetes is dependent on changes of BP or if interference with the renin-angiotensin system is, in itself, sufficient to explain the effects of ACE inhibition on UAER. We thus performed a 2-year study of the long-acting ACE inhibitor ramipril compared with placebo in normotensi...

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