Diabetes Care, Vol 23, Issue 1 64-69, Copyright © 2000 by American Diabetes Association

ARTICLES

Metabolic effects of troglitazone therapy in type 2 diabetic, obese, and lean normal subjects

JP Frias, JG Yu, YT Kruszynska and JM Olefsky
Division of Endocrinology and Metabolism, University of California, San Diego, La Jolla 92093, USA.

OBJECTIVE: To characterize metabolic effects of troglitazone in type 2 diabetic, obese, and lean subjects, and examine the effects of troglitazone 2-3 weeks after discontinuation. RESEARCH DESIGN AND METHODS: Nine type 2 diabetic, nine obese, and nine lean subjects underwent baseline metabolic studies including an 8-h meal-tolerance test (MTT) and a 5-h glucose clamp. Subjects then received troglitazone (600 mg/day) for 12 weeks and subsequently had repeat metabolic studies. Diabetic subjects remained off hypoglycemic agents for 2-3 weeks and then underwent a 5-h glucose clamp. RESULTS: In diabetic subjects, fasting plasma glucose was reduced (P<0.05) and insulin-stimulated glucose disposal (Rd) was enhanced by treatment (P<0.02). The area under the MTT 8-h plasma glucose curve declined with therapy (P<0.001), and its change was positively correlated with the improvement in Rd (r = 0.75, P<0.05). There was also a positive correlation between the change in fasting hepatic glucose output (HGO) and the change in fasting plasma glucose with treatment (r = 0.92, P<0.001). Discontinuation of therapy for 2-3 weeks did not significantly affect fasting plasma glucose or insulin-stimulated glucose Rd. In obese subjects, insulin-stimulated glucose Rd improved with therapy (P<0.001), allowing for maintenance of euglycemia by lower plasma insulin concentrations (P<0.05). In lean subjects, an increase in fasting HGO (P<0.001) and glucose clearance (P<0.01) was observed. CONCLUSIONS: Troglitazone lowers fasting and postprandial plasma glucose in type 2 diabetes by affecting both fasting HGO and peripheral insulin sensitivity. Its effects are evident 2-3 weeks after discontinuation. In obese subjects, its insulin sensitizing effects suggest a role for its use in the primary prevention of type 2 diabetes.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				G. K. Bandyopadhyay, J. G. Yu, J. Ofrecio, and J. M. Olefsky Increased Malonyl-CoA Levels in Muscle From Obese and Type 2 Diabetic Subjects Lead to Decreased Fatty Acid Oxidation and Increased Lipogenesis; Thiazolidinedione Treatment Reverses These Defects. Diabetes, August 1, 2006; 55(8): 2277 - 2285. [Abstract] [Full Text] [PDF]

				S. Dhindsa, D. Tripathy, N. Sanalkumar, S. Ravishankar, H. Ghanim, A. Aljada, and P. Dandona Free Fatty Acid-Induced Insulin Resistance in the Obese Is Not Prevented by Rosiglitazone Treatment J. Clin. Endocrinol. Metab., September 1, 2005; 90(9): 5058 - 5063. [Abstract] [Full Text] [PDF]

				G. K. Bandyopadhyay, J. G. Yu, J. Ofrecio, and J. M. Olefsky Increased p85/55/50 Expression and Decreased Phosphotidylinositol 3-Kinase Activity in Insulin-Resistant Human Skeletal Muscle Diabetes, August 1, 2005; 54(8): 2351 - 2359. [Abstract] [Full Text] [PDF]

				B. Kimmel and S. E. Inzucchi Oral Agents for Type 2 Diabetes: An Update Clin. Diabetes, April 1, 2005; 23(2): 64 - 76. [Abstract] [Full Text] [PDF]

				U. Kintscher and R. E. Law PPAR{gamma}-mediated insulin sensitization: the importance of fat versus muscle Am J Physiol Endocrinol Metab, February 1, 2005; 288(2): E287 - E291. [Abstract] [Full Text] [PDF]

				K. Levin, O. Hother-Nielsen, J. E. Henriksen, and H. Beck-Nielsen Effects of Troglitazone in Young First-Degree Relatives of Patients With Type 2 Diabetes Diabetes Care, January 1, 2004; 27(1): 148 - 154. [Abstract] [Full Text] [PDF]

				O. G. Kolterman, J. B. Buse, M. S. Fineman, E. Gaines, S. Heintz, T. A. Bicsak, K. Taylor, D. Kim, M. Aisporna, Y. Wang, et al. Synthetic Exendin-4 (Exenatide) Significantly Reduces Postprandial and Fasting Plasma Glucose in Subjects with Type 2 Diabetes J. Clin. Endocrinol. Metab., July 1, 2003; 88(7): 3082 - 3089. [Abstract] [Full Text] [PDF]

				J. G. Yu, S. Javorschi, A. L. Hevener, Y. T. Kruszynska, R. A. Norman, M. Sinha, and J. M. Olefsky The Effect of Thiazolidinediones on Plasma Adiponectin Levels in Normal, Obese, and Type 2 Diabetic Subjects Diabetes, October 1, 2002; 51(10): 2968 - 2974. [Abstract] [Full Text] [PDF]

				Y. Miyazaki, A. Mahankali, M. Matsuda, S. Mahankali, J. Hardies, K. Cusi, L. J. Mandarino, and R. A. DeFronzo Effect of Pioglitazone on Abdominal Fat Distribution and Insulin Sensitivity in Type 2 Diabetic Patients J. Clin. Endocrinol. Metab., June 1, 2002; 87(6): 2784 - 2791. [Abstract] [Full Text] [PDF]

				Y. Miyazaki, M. Matsuda, and R. A. DeFronzo Dose-Response Effect of Pioglitazone on Insulin Sensitivity and Insulin Secretion in Type 2 Diabetes Diabetes Care, March 1, 2002; 25(3): 517 - 523. [Abstract] [Full Text] [PDF]

				S. E. Inzucchi Oral Antihyperglycemic Therapy for Type 2 Diabetes: Scientific Review JAMA, January 16, 2002; 287(3): 360 - 372. [Abstract] [Full Text] [PDF]