The Tohoku Journal of Experimental Medicine
Online ISSN : 1349-3329
Print ISSN : 0040-8727
ISSN-L : 0040-8727
Regular Contributions
Pioglitazone (AD-4833) Ameliorates Insulin Resistance in Patients with NIDDM
Yoshimitsu Yamasaki, Ryuzo Kawamori, Taro Wasada, Akiko Sato, Yasue Omori, Hideyuki Eguchi, Makoto Tominaga, Hideo Sasaki, Masahiko Ikeda, Minoru Kubota, Yoshihiko Ishida, Toshiki Hozumi, Shigeaki Baba, Masaya Uehara, Motoaki Shichiri, Toshio Kaneko, Ad-4833 Glucose Clamp Study Group, Japan
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Keywords: pioglitazone, insulin resistance, lipid, glucose clamp
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1997 Volume 183 Issue 3 Pages 173-183

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Abstract

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 μmoles·kg−1·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·kg−1·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 (ρ=0.633), serum insulin (ρ=0.653), BMI (ρ=0.456), Rd (ρ=−0.558) and 1,5-AG (ρ=−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.

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