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To evaluate the pathophysiological significance of intra-abdominal fat accumulation in Japanese subjects with mild to moderate overweight, 107 subjects (56 men and 51 women, aged 16-68 years) with body mass index (BMI, kg/m2) of 17-39 (mean +/- SD, 25 +/- 4.3) were evaluated. Subjects with disorders which affect glucose metabolism, such as thyroid, adrenal, liver, and kidney diseases, were excluded. A 75 g oral glucose tolerance test (OGTT) was performed in all subjects, and venous samples were obtained before 15, 30, 60, 90 and 120 min after the glucose load for plasma glucose (PG), immunoreactive insulin (IRI) and C-peptide immunoreactivity (CPR) measurements. In 72 of the subjects, plasma free fatty acid (FFA) level at fasting was also determined. The degree of visceral fat accumulation was evaluated using a CT-scan by the method reported by Fujioka et al. (Metabolism, 36: 54-59, 1987), and intra-abdominal fat area/subcutaneous fat area (V/S ratio) was obtained. V/S ratio and BMI correlated positively in subjects with BMI less than 25 (17 men and 16 women, aged 28-62 years) but they did not correlate at all with each other in those with BMI greater than or equal to 25 (39 men and 35 women, aged 16-68 years). Based on this finding, the possible adverse effects of increased intra-abdominal fat on glucose metabolism were investigated in the subjects with BMI greater than or equal to 25. For this purpose, the correlation of V/S ratio with fasting PG (FPG), fasting IRI (FIRI), fasting CPR (FCPR), FPG/FIRI, FFA, or PG area (sigma PG) and sigma PG/sigma IRI at OGTT was analyzed. V/S ratio positively correlated with FPG, sigma PG, FPG/FIRI and sigma PG/sigma IRI but not with FFA. The correlation between V/S ratio and FIRI or FCPR was significant in the subjects with V/S ratio greater than or equal to 0.8 in men and greater than or equal to 0.4 in women. In sharp contrast to V/S ratio, BMI did not correlate at all with any of these metabolic indices. We conclude that in Japanese subjects with mild overweight to moderate obesity, intra-abdominal fat accumulation, but not the increase in the degree of obesity, accompanies worsening of glucose tolerance. Because PG elevation relative to IRI secretion is progressively greater with increasing V/S ratio, it is suggested that the deleterious effects of intra-abdominal fat accumulation can be attributed to increased insulin resistance.

The Effects of Body Fat Distribution on Glucose Tolerance in Overweight Subjects