Reduction of ACE activity is insufficient to decrease microalbuminuria in normotensive patients with type 1 diabetes

OBJECTIVE - To study whether administration of 1.25 and 5.0 mg ramipril dai ly, 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 = 19] and 5.0 mg [n = 18]), and compared with plac ebo [n = 18] after a single-blind placebo period of 1-4 weeks. The patients (total, n = 55, women, n = 14) were followed for 2 years. To document an e ffect on the renin-angiotensin system, ACE activity and plasma-renin activi ty (PRA) were measured. In addition, 24-h ambulatory blood pressure (BP) wa s recorded at baseline and repeated after 1 and 2 years using a Spacelab 90 207 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 < 0.05 for both) . On the other hand, neither ambulatory nor clinic BP was affected by eithe r dose of ramipril compared with the placebo group. There was no progressio n 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 group s at year 1 (P = 0.94) or year 2 (P = 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 cl inic 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.