Early ACE-i intervention in microalbuminuric patients with type 1 diabetes: effects on albumin excretion, 24 h ambulatory blood pressure, and renal function.
OBJECTIVE
To study the effects of ACE-i in type 1 diabetic patients with early microalbuminuria with regard to: i) UAE, ii) 24 h AMBP, including the effect on diurnal BP variation, and iii) renal haemodynamics.


METHODS
58 patients with urinary albumin excretion (UAE) between 20-70 microg/min were treated for two years with either the ACE inhibitor (ACE-i) lisinopril (20 mg od) or placebo in two randomised placebo controlled double blind studies. In a subgroup of patients (n=22) we performed 24 h ambulatory blood pressure measurements (AMBP) and renal function tests (constant infusion technique).


RESULTS
i) Changes in UAE over the two years were significantly different (p<0.01) in the two groups with final UAE in the lisinopril group of 19.1 microg/min x/divide 2.5 (geometric mean x/divide tolerance factor) and 44.1 microg/min x/divide 2.8 in the placebo group. In the lisinopril group 20 patients (60.6%) reversed to normoalbuminuria compared to 6 patients (24%) in the placebo group (p<0.02). ii) Clinical BP measurements revealed no differences between groups, but by AMBP significant reductions were detectable in the lisinopril group, primarily in night AMBP (systolic/diastolic: - 6.9 +/- 8.6/- 6.0 +/- 5.3 mmHg, p<0.01) as opposed to increases in the placebo group (3.1 +/- 9.3/1.9 +/- 7.3 mmHg). iii) Changes in UAE and changes in filtration fraction (FF) were positively correlated in the intervention group (r=0.9, p<0.01), i.e. the patients who showed the greatest fall in UAE were the ones with the greatest fall in FF.


CONCLUSIONS
ACE-i treatment in patients with low-grade microalbuminuria reduces 24 h AMBP without attenuating diurnal blood pressure variation, reduces UAE significantly, with changes in UAE being strongly associated with changes in FF. Furthermore, compared to placebo, ACE-i reverses micro- to normoalbuminuria in a significant fraction of patients.
Poulsen
P L
PL
Medical Department M, (Diabetes & Endocrinology), Aarhus, Denmark. Logstrup@dadlnet.dk
Ebbehøj
E
E
Nosadini
R
R
Fioretto
P
P
Deferrari
G
G
Crepaldi
G
G
Mogensen
C E
CE
D000328:Adult; D000419:Albuminuria; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D018660:Blood Pressure Monitoring, Ambulatory; D002940:Circadian Rhythm; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000503:physiopathology* / Q000652:urine; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology*; D006442:Glycated Hemoglobin / Q000032:analysis; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006801:Humans; D017706:Lisinopril / Q000627:therapeutic use*; D008297:Male; D010919:Placebos; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D006442:Glycated Hemoglobin; D017706:Lisinopril; D010919:Placebos