Effect of losartan on TGF-beta1 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 microg/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-beta1, 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 microg/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.


CONCLUSIONS
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.
Esmatjes
E
E
Diabetes Unit, Nephrology Department, Hospital Clinic Universitari, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Spain.
Flores
L
L
Iñigo
P
P
Lario
S
S
Ruilope
L M
LM
Campistol
J M
JM
D000419:Albuminuria; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D003925:Diabetic Angiopathies / Q000097:blood / Q000188:drug therapy / Q000652:urine; D003971:Diastole / Q000187:drug effects; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D013599:Systole / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000097:blood*
D000959:Antihypertensive Agents; D016212:Transforming Growth Factor beta; D019808:Losartan