Troglitazone improves whole-body insulin resistance and skeletal muscle glucose use in type II diabetic patients

Recently, troglitazone has emerged as an insulin sensitizer for the treatme nt of type II diabetes. However, its effect on skeletal muscle glucose use (SMGU) has not been studied. Methods: To investigate the effect of troglita zone on SMGU in patients with type II diabetes, we undertook skeletal muscl e F-18-FDG PET dynamic imaging under insulin clamping before and after admi nistration 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 129.9 +/- 9 .83 mu mol/min/kg) than in control subjects (55.6 +/- 16.5 mu mol/min/kg, P < 0.01), as was the SMGU (patients, 3.27 +/-: 2.17 mu mol/min/kg; control subjects, 10.9 +/- 6.4 mu mol/min/kg; P < 0.01). After the therapy, GDR sig nificantly improved in patients (29.3 +/- 14.6 mu mol/min/kg, P < 0.05), as did SMGU (5.96 +/- 2.11 mu mol/min/kg, P < 0.05). When results for patient s with and without hypertension were separately analyzed, a significant imp rovement in SMGU after troglitazone was seen in both normotensive and hyper tensive patients 9 normotensive [n = 10]: baseline, 3.67 +/- 2.89 mu mol/mi n/kg; after therapy, 5.28 +/- 2.57 mu mol/min/kg; P < 0.05; hypertensive [n = 10]: baseline, 2.89 +/- 1.22 mu mol/min/kg; after therapy, 4.72 +/- 1.39 mu mol/min/kg; P < 0.05). GDR in patients with and without hypertension wa s significantly improved by troglitazone (normotensive: baseline, 17.9 +/- 10.2 mu mol/min/kg; after therapy, 31.9 +/- 15.9 mu mol/min/kg; P < 0.01; h ypertensive: baseline, 39.6 +/- 15.1 mu mol/min/kg; after therapy, 47.7 +/- 23.8 mu mol/min/kg; P < 0.05). The plasma free fatty acid concentration du ring 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). Conclus ion: Troglitazone can improve whole-body insulin resistance through the imp rovement of SMGU but not through a decline in plasma free fatty acid concen tration in patients with type II diabetes with or without hypertension.