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 atherosclerosis through multiple risk factors such as insulin resistance, glucose intolerance, hyperlipidemia and hypertension. So far, it has been reported that a thaizolidinedione derivative, troglitazone, improves the insulin resistance in subjects with diabetes, glucose intolerance and obesity. However, it has not been reported yet that troglitazone affects fat distribution in subjects concomitant with visceral fat accumulation and multiple risk factors.


METHODS
Twenty-nine subjects with visceral fat accumulation who had at least two risk factors including glucose intolerance, hyperlipidemia and hypertension were investigated. They were randomly assigned to receive 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 serum cholesterol (T-chol), triglyceride (TG), HDL-cholesterol (HDL-C), and blood pressure, as well as the number of risk factors were measured periodically during the treatment. The change of the abdominal fat distribution was evaluated using computed tomographic scanning (CT scan) at the umbilicus level.


RESULTS
After the treatment for 12 weeks, the area under the curve (AUC) 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 pressure was significantly lower in subjects with hypertension in the pooled troglitazone group than in the placebo group (P<0.05). Therefore, the number of risk factors decreased with the troglitazone treatment. The ratio of visceral fat area (VFA) to subcutaneous fat area (SFA) (V/S ratio) decreased in the troglitazone groups due to decreased VFA and increased SFA.


CONCLUSIONS
These results suggest that thiazolidinedione derivative may be a useful drug to improve multiple risk factors by changing the fat distribution in subjects with visceral fat accumulation.
Nakamura
T
T
Department of Internal Medicine and Molecular Science, Graduate School of Medicine Osaka University, 2-2 Yamadaoka, Suita, 565-0871 Osaka, Japan. tadashi@imed2.med.osaka-u.ac.jp
Funahashi
T
T
Yamashita
S
S
Nishida
M
M
Nishida
Y
Y
Takahashi
M
M
Hotta
K
K
Kuriyama
H
H
Kihara
S
S
Ohuchi
N
N
Nishimura
T
T
Kishino
B I
BI
Ishikawa
K
K
Kawamoto
T
T
Tokunaga
K
K
Nakagawa
C
C
Mineo
I
I
Watanabe
F
F
Tarui
S
S
Matsuzawa
Y
Y
D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001823:Body Composition / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D002839:Chromans / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D018149:Glucose Intolerance / Q000188:drug therapy; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D006949:Hyperlipidemias / Q000188:drug therapy; D006973:Hypertension / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D014280:Triglycerides / Q000097:blood; D000077288:Troglitazone
D001786:Blood Glucose; D002784:Cholesterol; D002839:Chromans; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D013844:Thiazoles; D045162:Thiazolidinediones; D014280:Triglycerides; D000077288:Troglitazone