Pl. Poulsen et al., Lisinopril reduces albuminuria during exercise in low grade microalbuminuric type 1 diabetic patients: a double blind randomized study, J INTERN M, 249(5), 2001, pp. 433-440
Citations number
42
Categorie Soggetti
General & Internal Medicine","Medical Research General Topics
Background. Antihypertensive treatment is presently recommended in most typ
e 1 diabetic patients with microalbuminuria. The long-term effect of angiot
ensin converting enzymes (ACE) inhibitor (ACE-i) treatment on exercise urin
ary albumin excretion (E-UAE) and exercise blood pressure (E-BP) in type 1
diabetic patients with low grade microalbuminuria is not well documented. I
n addition, the possible predictive effect of baseline E-UAE on the progres
sion of overnight UAE remains to be clarified.
Design and Methods. In a randomized placebo controlled double blind study t
he effects of 2 years treatment with either lisinopril (20 mg o.d.) or plac
ebo was evaluated in 21 normotensive type 1 diabetic patients with overnigh
t UAE between 20 and 70 mug min(-1). Determinations of E-UAE and E-BP were
performed after exercise on an ergometercycle with a load of 70% of estimat
ed maximal VO2 for 20 min. Patients in the placebo and lisinopril groups we
re similar with regard to age (35.8 +/- 11.3 vs. 29.3 +/- 8.6 years), durat
ion of diabetes (19.4 +/- 8.2 vs. 16.8 +/- 5.3 years), and HbA(1c) (9.0 +/-
1.0 vs. 9.4 +/- 1.7%).
Results. At baseline, E-UAE was similar in the two groups (placebo: 150.1 x
/divided by 3.7, lisinopril: 96.8 x/divided by 1.8 mug min(-1) (geometric m
ean x/divided by tolerance factor)). After 2 years treatment E-UAE had incr
eased in the placebo group, whereas E-UAE was reduced in the lisinopril tre
ated patients (placebo: 213.6 x/divided by 6.9, lisinopril: 48.3 x/divided
by 3.1 mug min(-1), P = 0.04). The relative increase in E-UAE (E-UAE/Pre-ex
ercise UAE) was similar at baseline in both groups (3.7 x/divided by 2.3 vs
. 2.8 x/divided by 2.0) but significantly higher in the placebo group after
2 years (4.4 x/divided by 2.4 compared with 1.6 x/divided by 1.7 in the li
sinopril group, P < 0.01) These changes over two years in relative increase
in E-UAE were significantly different (P = 0.03). Exercise blood pressure
was similar in both groups at baseline and over 2 years increased in the pl
acebo group (from 166.5 <plus/minus> 15.1-179.9 +/- 35.6 mmHg), in contrast
to the lsinopril group where E-BP was slightly reduced (from 168.5 +/- 20.
6-165.1 +/- 16.6 mmHg) but the difference in blood pressure over the 2 year
s did not reach statistical significance. Exercise urinary albumin excretio
n and,E-BP were closely associated (correlation for year 2: r = 0.734, P <
0.001), and also changes over the 2 years in E-UAE and E-BP were positively
correlated (r = 0.53,P = 0.01). At year 2, overnight UAE, pre-exercise UAE
(pre-E-UAE), E-UAE and E-BP were all closely linked (r-values between 0.6
and 0.9, P-values <0.01). In the prediction of changes in overnight UAE ove
r 2 years, neither baseline E-UAE nor baseline E-BP conveyed explanatory in
formation in comparison with baseline overnight UAE and HbA(1c).
Conclusions. In type 1 diabetic patients with low-grade microalbuminuria, 2
years of ACE-i treatment with lisinopril significantly reduced E-UAE. Stro
ng correlations were found between E-UAE and E-BP and also changes over 2 y
ears in these parameters were significantly associated.