Efficacy of troglitazone on body fat distribution in type 2 diabetes

• Published in: Diabetes care Vol. 23; no. 8; pp. 1067 - 1071
• Main Authors: AKAZAWA, S, FUYAN SUN, ITO, M, KAWASAKI, E, EGUCHI, K
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.08.2000
• Subjects: Adipose Tissue - anatomy & histology; Adipose Tissue - drug effects; Adipose tissues; Biological and medical sciences; Body fat; Body Mass Index; C-Peptide - blood; Chromans - therapeutic use; Diabetes Mellitus - physiopathology; Diabetes Mellitus, Type 2 - diagnostic imaging; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - physiopathology; Drug therapy; Female; Glycated Hemoglobin A - analysis; Hormones. Endocrine system; Humans; Hypoglycemic Agents - therapeutic use; Insulin - metabolism; Insulin Secretion; Male; Measurement; Medical sciences; Middle Aged; Obesity; Pharmacology. Drug treatments; Physiological aspects; Sex Characteristics; Thiazoles - therapeutic use; Thiazolidinediones; Tomography, X-Ray Computed; Troglitazone; Type 2 diabetes; Viscera; Weight Gain; Japan; Endocrinopathy; Human; Treatment efficiency; Non insulin dependent diabetes; Fat mass; Body composition; Chemotherapy; Hypoglycemic agent; Treatment; Distribution; Adult; Predictive factor; Elderly; Troglitazone
• ISSN: 0149-5992; 1935-5548
• DOI: 10.2337/diacare.23.8.1067

Efficacy of troglitazone on body fat distribution in type 2 diabetes. S Akazawa , F Sun , M Ito , E Kawasaki and K Eguchi Unit of Metabolism/Diabetes and Clinical Nutrition, Nagasaki University School of Medicine, Japan. akazawa@net.nagasaki-u.ac.jp Abstract OBJECTIVE: The insulin-sensitizing action of troglitazone may be mediated through the activation of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and the promotion of preadipocyte differentiation in adipose tissue on which troglitazone has depot-specific effects. We investigated the relationship between efficacy of the drug and body fat distribution. Changes in body fat distribution were also investigated by long-term administration of the drug. RESEARCH DESIGN AND METHODS: Troglitazone was given at a dose of 400 mg/day to 20 patients with type 2 diabetes whose diet and sulfonylurea therapy produced unsatisfactory glycemic control (HbA(1c) >7.8%) and whose insulin secretory capacity was found to be preserved (postprandial C-peptide >3 ng/ml). HbA(1c) values, serum lipid levels, and body weight were measured monthly Body fat distribution was evaluated in subcutaneous (SC) and visceral fat using a computed tomography scan at umbilical levels before and after troglitazone therapy RESULTS: During the 1-year troglitazone treatment, HbA(1c) was significantly decreased (from 9.2 +/- 0.2 to 7.1 +/- 0.2%, P < 0.01), showing lowest values at 4-6 months, whereas body weight was significantly increased (BMI 24.6 +/- 0.6 to 25.7 +/- 0.6 kg/m2, P < 0.01). Reduction of HbA(1c) (deltaHbA(1c)) from the baseline value during treatment was significantly greater in obese patients (BMI >26 kg/m2) than in nonobese patients (-3.2 +/- 0.4 vs. -2.1 +/- 0.3%, P < 0.05) and was more significant in women than in men (-3.2 +/- 0.2 vs. - 1.4 +/- 0.2%, P < 0.01). The level of deltaHbA(1c) during treatment showed a significant negative correlation with SC fat area (r = -0.742, P < 0.01) but not with visceral fat area. Weight gain during troglitazone treatment resulted in increased accumulation of SC fat without a change in visceral fat area and, consequently. in a significant decrease in the visceral-to-SC fat ratio. CONCLUSIONS: Predominant accumulation of SC fat for the visceral fat tissue was an important predictor of the efficacy of troglitazone therapy in patients with type 2 diabetes. Greater efficacy of troglitazone was observed in women who were characterized by more accumulation of SC adipose tissue than men. Long-term administration of the drug resulted in weight gain with increased accumulation of SC adipose tissue, probably because of the activation of PPAR-gamma in the region.