Rosiglitazone but Not Metformin Enhances Insulin- and Exercise-Stimulated Skeletal Muscle Glucose Uptake in Patients With Newly Diagnosed Type 2 Diabetes

• Published in: Diabetes (New York, N.Y.) Vol. 51; no. 12; pp. 3479 - 3485
• Main Authors: Hällsten, Kirsti, Virtanen, Kirsi A, Lönnqvist, Fredrik, Sipilä, Hannu, Oksanen, Airi, Viljanen, Tapio, Rönnemaa, Tapani, Viikari, Jorma, Knuuti, Juhani, Nuutila, Pirjo
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.12.2002
• Subjects: Biological and medical sciences; Blood Glucose - analysis; Body Weight - drug effects; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - pathology; Dose-Response Relationship, Drug; Drug therapy; Exercise - physiology; Fasting - blood; Female; Fundamental and applied biological sciences. Psychology; Glucose - metabolism; Glycated Hemoglobin A - analysis; Humans; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - therapeutic use; Insulin - blood; Insulin - therapeutic use; Leg; Male; Medicin och hälsovetenskap; Metformin; Metformin - administration & dosage; Metformin - therapeutic use; Middle Aged; Muscle, Skeletal - diagnostic imaging; Muscle, Skeletal - metabolism; Oxygen Consumption - drug effects; Physiological aspects; Radionuclide Imaging; Rosiglitazone; Rosiglitazone maleate; Thiazoles - administration & dosage; Thiazoles - therapeutic use; Thiazolidinediones; Type 2 diabetes
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diabetes.51.12.3479

Rosiglitazone but Not Metformin Enhances Insulin- and Exercise-Stimulated Skeletal Muscle Glucose Uptake in Patients With Newly Diagnosed Type 2 Diabetes Kirsti Hällsten 1 , Kirsi A. Virtanen 1 , Fredrik Lönnqvist 2 , Hannu Sipilä 1 , Airi Oksanen 3 , Tapio Viljanen 1 , Tapani Rönnemaa 4 , Jorma Viikari 4 , Juhani Knuuti 1 and Pirjo Nuutila 1 1 Turku PET Centre, University of Turku, Turku, Finland 2 Huddinge University Hospital, Karolinska Institute, Stockholm, Sweden 3 Department of Physical Medicine and Rehabilitation, University of Turku, Turku, Finland 4 Department of Medicine, University of Turku, Turku, Finland Abstract Rosiglitazone, a thiazolidinedione, enhances peripheral insulin sensitivity in patients with type 2 diabetes. Because the synergic action of insulin and exercise has been shown to be decreased in insulin resistance, the aim of this study was to compare the effects of rosiglitazone and metformin on muscle insulin responsiveness at rest and during exercise in patients with type 2 diabetes. Therefore, 45 patients with newly diagnosed or diet-treated type 2 diabetes were randomized for treatment with rosiglitazone (4 mg b.i.d.), metformin (1 g b.i.d.), or placebo in a 26-week double-blind trial. Skeletal muscle glucose uptake was measured using fluorine-18-labeled fluoro-deoxy-glucose and positron emission tomography (PET) during euglycemic-hyperinsulinemic clamp and one-legged exercise before and after the treatment period. Rosiglitazone ( P < 0.05) and metformin ( P < 0.0001) treatment lowered the mean glycosylated hemoglobin. The skeletal muscle glucose uptake was increased by 38% ( P < 0.01) and whole-body glucose uptake by 44% in the rosiglitazone group. Furthermore, the exercise-induced increment during insulin stimulation was enhanced by 99% ( P < 0.0001). No changes were observed in skeletal muscle or whole-body insulin sensitivity in the metformin group. In conclusion, rosiglitazone but not metformin 1 ) improves insulin responsiveness in resting skeletal muscle and 2 ) doubles the insulin-stimulated glucose uptake rate during physical exercise in patients with type 2 diabetes. Our results suggest that rosiglitazone improves synergic action of insulin and exercise. Footnotes Address correspondence and reprint requests to Dr. Pirjo Nuutila, PhD, Turku PET Centre, University of Turku, PO Box 52, FIN-20521 Turku, Finland. E-mail: pirjo.nuutila{at}utu.fi . Received for publication 17 May 2002 and accepted in revised form 5 September 2002. FFA, free fatty acid; [ 18 F]FDG, fluorine-18-labeled fluoro-deoxy-glucose; [ 15 O]H 2 O, oxygen-15-labeled water; [ 15 O]O 2 , oxygen-15-labeled oxygen; PET, positron emission tomography; PI, phosphatidylinositol; PPAR, peroxisome proliferator-activated receptor; t 1/2 , half-life; TZD, thiazolidinedione. DIABETES