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Troglitazone Improves Whole-Body Insulin Resistance and Skeletal Muscle Glucose Use in Type II Diabetic Patients

Departments of Cardiovascular Medicine and Radiology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan

Recently, troglitazone has emerged as an insulin sensitizer for the treatment of type II diabetes. However, its effect on skeletal muscle glucose use (SMGU) has not been studied. Methods: To investigate the effect of troglitazone on SMGU in patients with type II diabetes, we undertook skeletal muscle ¹⁸F-FDG PET dynamic imaging under insulin clamping before and after administration of SMGU to 20 patients with type II diabetes. Data were compared with those for 12 age-matched healthy volunteers. Results: The whole-body glucose disposal rate (GDR) was significantly lower in patients (29.9 ± 9.83 µmol/min/kg) than in control subjects (55.6 ± 16.5 µmol/min/kg, P < 0.01), as was the SMGU (patients, 3.27 ± 2.17 µmol/min/kg; control subjects, 10.9 ± 6.4µmol/min/kg; P < 0.01). After the therapy, GDR significantly improved in patients (29.3 ± 14.6 µmol/min/kg, P < 0.05), as did SMGU (5.06 ± 2.11 µmol/min/kg, P < 0.05). When results for patients with and without hypertension were separately analyzed, a significant improvement in SMGU after troglitazone was seen in both normotensive and hypertensive patients (normotensive [n = 10]: baseline, 3.67 ± 2.89 µmol/min/kg; after therapy, 5.28 ± 2.61 µmol/min/kg; P < 0.05; hypertensive [n = 10]: baseline, 2.89 ± 1.22 µmol/min/kg; after therapy, 4.72 ± 1.39 µmol/min/kg; P < 0.05). GDR in patients with and without hypertension was significantly improved by troglitazone (normotensive: baseline, 17.9 ± 10.2 µmol/min/kg; after therapy, 31.9 ± 15.9 µmol/min/kg; P < 0.01; hypertensive: baseline, 39.6 ± 15.1 µmol/min/kg; after therapy, 47.7 ± 23.8 µmol/min/kg; P < 0.05). The plasma free fatty acid concentration during insulin clamping was not changed by troglitazone (baseline, 1.1 ± 0.86 mEq/L; after therapy, 0.93 ± 0.65 mEq/L; P = not significant). Conclusion: Troglitazone can improve whole-body insulin resistance through the improvement of SMGU but not through a decline in plasma free fatty acid concentration in patients with type II diabetes with or without hypertension.

Key Words: troglitazone • insulin resistance • skeletal muscle glucose metabolism • PET • insulin sensitizer • type II diabetes

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