Differential Effects of Rosiglitazone and Metformin on Adipose Tissue Distribution and Glucose Uptake in Type 2 Diabetic Subjects

• Published in: Diabetes (New York, N.Y.) Vol. 52; no. 2; pp. 283 - 290
• Main Authors: Virtanen, Kirsi A, Hällsten, Kirsti, Parkkola, Riitta, Janatuinen, Tuula, Lönnqvist, Fredrik, Viljanen, Tapio, Rönnemaa, Tapani, Knuuti, Juhani, Huupponen, Risto, Lönnroth, Peter, Nuutila, Pirjo
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.02.2003
• Subjects: Adipose Tissue - diagnostic imaging; Adipose Tissue - drug effects; Adipose Tissue - metabolism; Aged; Biological and medical sciences; Blood Glucose - metabolism; Body fat; Body Weight; Care and treatment; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Drug therapy; Evaluation; Female; Fluorodeoxyglucose F18 - pharmacokinetics; General and cellular metabolism. Vitamins; Glucose - metabolism; Humans; Hypoglycemic Agents - therapeutic use; Insulin - physiology; Insulin resistance; Kinetics; Lactates - blood; Lipids - blood; Male; Medical sciences; Metformin; Metformin - therapeutic use; Middle Aged; Pharmacology. Drug treatments; Placebos; Radiopharmaceuticals - pharmacokinetics; Rosiglitazone; Rosiglitazone maleate; Thiazoles - therapeutic use; Thiazolidinediones; Tomography, Emission-Computed; Type 2 diabetes; Weight Loss; Finland; Endocrinopathy; Human; Biguanides; Adipose tissue; Rosiglitazone; Thiazolidinedione derivatives; Metformin; Non insulin dependent diabetes; Biological activity
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diabetes.52.2.283

Differential Effects of Rosiglitazone and Metformin on Adipose Tissue Distribution and Glucose Uptake in Type 2 Diabetic Subjects Kirsi A. Virtanen 1 , Kirsti Hällsten 1 , Riitta Parkkola 2 , Tuula Janatuinen 1 , Fredrik Lönnqvist 3 , Tapio Viljanen 1 , Tapani Rönnemaa 4 , Juhani Knuuti 1 , Risto Huupponen 5 , Peter Lönnroth 6 and Pirjo Nuutila 1 4 1 Turku PET Centre, University of Turku and Turku University Hospital, Turku, Finland 2 Department of Radiology, University of Turku and Turku University Hospital, Turku, Finland 3 Karolinska Institutet, Stockholm, Sweden 4 Department of Medicine, University of Turku and Turku University Hospital, Turku, Finland 5 Department of Pharmacology and Clinical Pharmacology, University of Turku and Turku University Hospital, Turku, Finland 6 Department of Medicine, University of Gothenburg, Gothenburg, Sweden Abstract We evaluated the effects of rosiglitazone (4 mg b.i.d.) and metformin (1 g b.i.d.) monotherapy for 26 weeks on adipose tissue insulin-stimulated glucose uptake in patients ( n = 41) with type 2 diabetes. Before and after the treatment, glucose uptake was measured using 2-[ 18 F]fluoro-2-deoxyglucose and positron emission tomography and adipose tissue masses were quantified using magnetic resonance imaging. Rosiglitazone improved insulin-stimulated whole-body glucose uptake by 44% ( P < 0.01 vs. placebo). Mean body weight was unchanged in the rosiglitazone group, while it decreased by 2.0 kg in the metformin group ( P < 0.05 vs. placebo). In visceral adipose tissue, glucose uptake increased by 29% (from 17.8 ± 2.0 to 23.0 ± 2.6 μmol · kg −1 · min −1 , P < 0.05 vs. placebo) in the rosiglitazone group but to a lesser extent (17%) in the metformin group (from 16.2 ± 1.5 to 18.9 ± 1.7 μmol · kg −1 · min −1 , P < 0.05 vs. baseline). Because the visceral adipose tissue mass simultaneously decreased with both treatments ( P < 0.05), no change was observed in total visceral glucose uptake per depot. Rosiglitazone significantly enhanced glucose uptake in the femoral subcutaneous area, either when expressed per tissue mass (from 10.8 ± 1.2 to 17.1 ± 1.7 μmol · kg −1 · min −1 , P < 0.01 vs. placebo) or per whole-fat depot ( P < 0.05 vs. placebo). In conclusion, metformin treatment resulted in improvement of glycemic control without enhancement of peripheral insulin sensitivity. The improved insulin sensitivity of the nonabdominal subcutaneous adipose tissue during treatment with rosiglitazone partly explains the enhanced whole-body insulin sensitivity and underlies the central role of adipose tissue for action of peroxisome proliferator-activated receptor γ agonist in vivo. Footnotes Address correspondence and reprint requests to Dr. Pirjo Nuutila, Turku PET Centre, University of Turku, PO Box 52, 20521 Turku, Finland. E-mail: pirjo.nuutila{at}utu.fi . Received for publication 28 August 2002 and accepted in revised form 6 November 2002. F.L. is a former employee of SmithKlineBeecham and GlaxoSmithKline (until 30 June 2001). [ 18 F]FDG, 2-[ 18 F]fluoro-2-deoxyglucose; FFA, free fatty acid; MRI, magnetic resonance imaging; PET, positron emission tomography; PPAR, peroxisome proliferator-activated receptor; ROI, region of interest; TZD, thiazolidinedione. DIABETES