Thiazolidinedione derivative improves fat distribution and multiple risk factors in subjects with visceral fat accumulation - double-blind placebo-controlled trial

Background: It has been clarified that visceral fat accumulation leads to a therosclerosis through multiple risk factors such as insulin resistance, gl ucose intolerance, hyperlipidemia and hypertension. So far, it has been rep orted that a thaizolidinedione derivative, troglitazone, improves the insul in resistance in subjects with diabetes, glucose intolerance and obesity. H owever, it has not been reported yet that troglitazone affects fat distribu tion in subjects concomitant with visceral fat accumulation and multiple ri sk factors. Methods: Twenty-nine subjects with visceral fat accumulation wh o had at least two risk factors including glucose intolerance, hyperlipidem ia and hypertension were investigated. They were randomly assigned to recei ve either 200 or 400 mg per day of troglitazone or placebo for 12 weeks. A 75 g oral glucose tolerance test (OGTT) was performed before and after the treatment for 12 weeks. Fasting plasma glucose, insulin, HbA(1c), total ser um cholesterol (T-chol), triglyceride (TG), HDL-cholesterol (HDL-C), and bl ood pressure. as well as the number of risk factors were measured periodica lly during the treatment. The change of the abdominal fat distribution was evaluated using computed tomographic scanning (CT scan) at the umbilicus le vel. Results: After the treatment for 12 weeks, the area under the curve (A UC) of plasma glucose from a 75 g OGTT decreased dose-dependently. HbA(1c) and TG decreased significantly in the high-dose troglitazone group (400 mg per day) compared with the placebo group (P < 0.05). Systolic blood pressur e was significantly lower in subjects with hypertension in the pooled trogl itazone group than in the placebo group (P < 0.05). Therefore. the number o f risk factors decreased with the troglitazone treatment. The ratio of visc eral fat area (VFA) to subcutaneous fat area (SFA) ( VIS ratio) decreased i n the troglitazone groups due to decreased VFA and increased SFA. Conclusio n: These results suggest that thiazolidinedione derivative may be a useful drug to improve multiple risk factors by changing the fat distribution in s ubjects with visceral fat accumulation. <(c)> 2001 Elsevier Science Ireland Ltd. All rights reserved.