Efficacy of troglitazone on body fat distribution in type 2 diabetes.
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.


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.
Unit of Metabolism/Diabetes and Clinical Nutrition, Nagasaki University School of Medicine, Japan. akazawa@net.nagasaki-u.ac.jp
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S
Akazawa
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Sun
M
M
Ito
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Kawasaki
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K
Eguchi
D000273:Adipose Tissue / Q000033:anatomy & histology / Q000187:drug effects*; D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood; D002839:Chromans / Q000627:therapeutic use*; D003920:Diabetes Mellitus / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology*; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D008297:Male; D008875:Middle Aged; D009765:Obesity; D012727:Sex Characteristics; D013844:Thiazoles / Q000627:therapeutic use*; D045162:Thiazolidinediones; D014057:Tomography, X-Ray Computed; D000077288:Troglitazone; D014781:Viscera; D015430:Weight Gain
D002096:C-Peptide; D002839:Chromans; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D013844:Thiazoles; D045162:Thiazolidinediones; D000077288:Troglitazone