Pioglitazone (AD-4833) ameliorates insulin resistance in patients with NIDDM. AD-4833 Glucose Clamp Study Group, Japan.
We evaluated the effect of pioglitazone, a thiazolidinedione compound, on insulin-stimulated glucose disposal (Rd) and its efficacy on carbohydrate and lipid metabolism in patients with non-insulin-dependent diabetes mellitus (NIDDM). Twenty NIDDM subjects (mean age 58.2+/-9.4 year, body mass index (BMI) 23.9+/-3.4 kg/ m2 (mean+/-S.D.], three with diet alone, 17 with sulfonylureas [SU]) participated in this trial from five diabetes clinics. Euglycemic (5.3 mmol/liter) hyperinsulinemic (insulin infusion rate 9 micromoles x kg[-1] x min[-1]) clamp studies were performed before and after oral administration of pioglitazone (30 mg/day) for 87+/-10 days. The Rd significantly improved from 5.5+/-2.5 to 8.3+/-3.1 mg x kg(-1) x min(-1). Fasting plasma glucose (FPG) level significantly decreased from 11.0+/-2.0 mmol/liter to 8.9+/-1.1 mmol/liter with a significant improvement in the hemoglobin A1c level from 9.2+/-1.8% to 8.3+/-1.5%. Fasting serum insulin and C peptide levels decreased from 83+/-36 pmol/liter and 0.62+/-0.21 nmol/liter to 66+/-29 pmol/liter and 0.58+/-0.25 nmol/liter, respectively. Fasting serum triglyceride and free fatty acids levels significantly decreased with concomitant increase of fasting serum HDL-cholesterol levels from 1.2+/-0.2 to 1.5+/-0.3 mmol/liter. The change in Rd between before and after pioglitazone administration correlated with baseline values of FPG (rho=0.633), serum insulin (rho=0.653), BMI (rho=0.456), Rd (rho 0.558) and 1,5-AG (rho=-0.522). These data indicate that pioglitazone enhances the insulin action in NIDDM patients on diet alone or SU, and thereby improves both plasma glucose level and lipid profiles.
Yamasaki
Y
Y
The First Department of Medicine, Osaka University Medical School, Yamadaoka, Suita, Japan.
Kawamori
R
R
Wasada
T
T
Sato
A
A
Omori
Y
Y
Eguchi
H
H
Tominaga
M
M
Sasaki
H
H
Ikeda
M
M
Kubota
M
M
Ishida
Y
Y
Hozumi
T
T
Baba
S
S
Uehara
M
M
Shichiri
M
M
Kaneko
T
T
D000284:Administration, Oral; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D000077205:Pioglitazone; D013844:Thiazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D045162:Thiazolidinediones
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D013844:Thiazoles; D045162:Thiazolidinediones; D000077205:Pioglitazone