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 daily, compared with placebo treatment, reduces the urinary albumin excretion rate (UAER) in normotensive patients with type 1 diabetes.


METHODS
Ramipril was administered double blind at two different doses (1.25 [n = 19] and 5.0 mg [n = 18]), and compared with placebo (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 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 < 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 = 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 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.
Bojestig
M
M
Department of Medicine and Care, University Hospital of Linköping, Sweden.
Karlberg
B E
BE
Lindström
T
T
Nystrom
F H
FH
D000419:Albuminuria / Q000517:prevention & control*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000503:physiopathology* / Q000652:urine; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D010919:Placebos; D017257:Ramipril / Q000009:adverse effects / Q000627:therapeutic use*; D012083:Renin / Q000097:blood; D016037:Single-Blind Method; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D010919:Placebos; D007703:Peptidyl-Dipeptidase A; D012083:Renin; D017257:Ramipril