Comparative effects of pioglitazone, glibenclamide, and voglibose on urinary endothelin-1 and albumin excretion in diabetes patients.
Urinary endothelin (ET)-1 excretion is present in non-insulin dependent diabetes (NIDDM) patients with microalbuminuria, and an increase in circulating ET-1 precedes the microalbuminuric phase of renal injury related to diabetes. The aim of the present study was to determine whether various drugs alter urinary ET-1 levels and urinary albumin excretion (UAE) in NIDDM patients with microalbuminuria. Forty-five NIDDM patients with microalbuminuria were randomly assigned to three groups: those treated with pioglitazone at 30 mg/day (n=15), those treated with glibenclamide at 5 mg/day (n=15), and those treated with voglibose at 0.6 mg/day (n=15). Patients received these drugs for 3 months. UAE, urinary ET-1, and plasma ET-1 levels were measured in these patients before and after treatment. Before treatment, UAE, urinary ET-1, and plasma ET-1 levels differed little among the three groups. UAE in the 45 NIDDM patients (156.2+/-42.8 microg/min) was greater than that in 30 healthy controls (8.2+/-2.6 microg/min) (P<.001). Urinary ET-1 levels in the NIDDM patients (8.7+/-1.3 ng/g urinary creatinine (UC)) were significantly higher than that in the controls (2.4+/-0.2 ng/g UC) (P<.01). Plasma ET-1 levels, however, in the NIDDM patients (1.3+/-0.4 pg/ml) did not differ significantly from the levels in healthy controls (1.0+/-0.6 pg/ml). Pioglitazone but no glibenclamide or voglibose reduced UAE from 142.8+/-42.2 to 48. 4+/-18.2 microg/min (P<.01) and urinary ET-1 levels from 8.6+/-1.3 to 3.4+/-0.5 ng/g UC (P<.01). These data suggest pioglitazone to be effective in reducing UAE and urinary ET-1 concentrations in NIDDM patients with microalbuminuria.
Nakamura
T
T
Department of Medicine, Misato Junshin Hospital, 745 Kobo, Saitama, Misato, Japan.
Ushiyama
C
C
Shimada
N
N
Hayashi
K
K
Ebihara
I
I
Koide
H
H
D000419:Albuminuria; D001794:Blood Pressure / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology / Q000652:urine*; D019332:Endothelin-1 / Q000652:urine*; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005905:Glyburide / Q000494:pharmacology / Q000627:therapeutic use*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007294:Inositol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D000077205:Pioglitazone; D012016:Reference Values; D013844:Thiazoles / Q000494:pharmacology / Q000627:therapeutic use*; D045162:Thiazolidinediones
D019332:Endothelin-1; D004791:Enzyme Inhibitors; D005905:Glyburide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007294:Inositol; D000077205:Pioglitazone; D013844:Thiazoles; D045162:Thiazolidinediones; C102817:voglibose