Effect of losartan on TGF-β1 and urinary albumin excretion in patients with type 2 diabetes mellitus and microalbuminuria

Background. The aim of the present study was to determine the effect of losartan on transforming growth factor-beta1 (TGF-beta1) plasma levels and urinary albumin excretion (UAE) in patients with type 2 diabetes mellitus, mild hypertension and microalbuminuria. Methods. Fourteen patients (eight males, aged 55+/-6 years) with type 2 diabetes mellitus, mild arterial hypertension and microalbuminuria, participating in an open, uncontrolled, pilot study were included. Patients were treated for 8 weeks with losartan. TGF-beta1 plasma levels, UAE and 24-h blood pressure monitoring were determined at baseline and at 4 and 8 weeks. Results. At 4 and 8 weeks of treatment, a reduction was observed in TGF-beta1 plasma levels (5.5+/-4.5 vs 2.0 +/- 0.6 and 2.6 +/- 1.0 ng/ml, P < 0.005), UAE (96 +/- 65 vs 59 +/- 59. and 64 +/- 47 <mu>g/min, P < 0.01), 24-h systolic blood pressure (136 +/- 9 vs 129 +/- 9 and 130 +/- 10 mmHg, P < 0.01) and 24-h diastolic blood pressure (77 +/- 9 vs 74 +/- 8 and 74 +/- 7 mmHg, P < 0.03). Stratifying the patients by baseline TGF-<beta>1, seven had TGF-beta1 plasma values higher than normal controls. At 4 and 8 weeks, they showed a marked reduction in TGF-beta1 values (9.0 +/- 3.9 to 2.1 +/- 0.7 and 2.5 +/- 0.7 ng/ml, P < 0.01) and UAE (106 +/- 83 to 49 +/- 42 and 38 +/- 26 <mu>g/min, P < 0.05), with good correlation between the percentage reduction of both parameters (r=0.83, P<0.01). The remaining seven patients, with normal baseline TGF-beta1 plasma levels, showed no change in TGF-beta1 plasma levels and UAE after treatment. Conclusion. Treatment with losartan decreases TGF-beta1 plasma values and UAE in type 2 diabetes mellitus patients with high baseline TGF-beta1 levels, suggesting that TGF-beta1 may be a marker to detect patients who may particularly benefit from renin angiotensin system blockade.