Lisinopril reduces albuminuria during exercise in low grade microalbuminuric type 1 diabetic patients: a double blind randomized study.

Background: Antihypertensive treatment is presently recommended in most type 1 diabetic patients with microalbuminuria. The long-term effect of angiotensin converting enzymes (ACE) inhibitor (ACE-i) treatment on exercise urinary albumin excretion (E-UAE) and exercise blood pressure (E-BP) in type 1 diabetic patients with low grade microalbuminuria is not well documented. In addition, the possible predictive effect of baseline E-UAE on the progression of overnight UAE remains to be clarified.

Design And Methods: In a randomized placebo controlled double blind study the effects of 2 years treatment with either lisinopril (20 mg o.d.) or placebo was evaluated in 21 normotensive type 1 diabetic patients with overnight UAE between 20 and 70 microg min-1. Determinations of E-UAE and E-BP were performed after exercise on an ergometercycle with a load of 70% of estimated maximal VO2 for 20 min. Patients in the placebo and lisinopril groups were similar with regard to age (35.8 +/- 11.3 vs. 29.3 +/- 8.6 years), duration of diabetes (19.4 +/- 8.2 vs. 16.8 +/- 5.3 years), and HbA1c (9.0 +/- 1.0 vs. 9.4 +/- 1.7%).

Results: At baseline, E-UAE was similar in the two groups (placebo: 150.1 x or divide 3.7, lisinopril: 96.8 x or divide 1.8 microg min-1 (geometric mean x or divide tolerance factor)). After 2 years treatment E-UAE had increased in the placebo group, whereas E-UAE was reduced in the lisinopril treated patients (placebo: 213.6 x or divide 6.9, lisinopril: 48.3 x or divide 3.1 microg min-1, P = 0.04). The relative increase in E-UAE (E-UAE/Pre-exercise UAE) was similar at baseline in both groups (3.7 x or divide 2.3 vs. 2.8 x or divide 2.0) but significantly higher in the placebo group after 2 years (4.4 x or divide 2.4 compared with 1.6 x or divide 1.7 in the lisinopril 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 placebo group (from 166.5 +/- 15.1-179.9 +/- 35.6 mmHg), in contrast to the lisinopril 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 years did not reach statistical significance. Exercise urinary albumin excretion 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 over 2 years, neither baseline E-UAE nor baseline E-BP conveyed explanatory information in comparison with baseline overnight UAE and HbA1c.

Conclusions: In type 1 diabetic patients with low-grade microalbuminuria, 2 years of ACE-i treatment with lisinopril significantly reduced E-UAE. Strong correlations were found between E-UAE and E-BP and also changes over 2 years in these parameters were significantly associated.