Macor C, Ruggeri A, Mazzonetto P, Federspil G, Cobelli C, Vettor R
Institute of Semeiotica Medica, Patologia Medica III, Department of Electronics and Informatics, University of Padua, Italy.
Metabolism. 1997 Feb;46(2):123-9. doi: 10.1016/s0026-0495(97)90288-2.
In obesity, a central pattern of fat distribution is mostly associated with hyperinsulinemia, insulin resistance, and hyperlipemia, thus promoting the development of non-insulin-dependent diabetes mellitus and cardiovascular disease. In addition, in obesity, changes in energy expenditure are hypothesized to be involved in the development or maintenance of excessive body fat storage. In this study, abdominal fat distribution by computed tomographic (CT) scan was used to study the relation between the visceral fat depot, insulin secretion, and insulin sensitivity in a group of obese subjects with normal glucose tolerance (n = 26; body mass index [BMI], 39 +/- 1 kg/m2) and a group of normal-weight control subjects (n = 9; BMI, 23 +/- 1 kg/m2). The minimal model method was used to assess insulin sensitivity, S(I), and first-phase (phi1) and second-phase (phi2) beta-cell sensitivity from plasma glucose, insulin, and C-peptide concentrations measured during an intravenous glucose tolerance test ([IVGTT] 0.33 g/kg body weight). Moreover, we evaluated the relationships between these parameters and the resting metabolic rate (RMR) and glucose-induced thermogenesis (GIT) measured by indirect calorimetry. The data show the following: (1) in obese subjects, phi1 is greater but not statistically different from the value in control subjects (252 +/- 41 v 157 +/- 25 dimensionless 10(9)); (2) phi2 is significantly higher in obese subjects (27 +/- 4 v 14 +/- 2 min(-1) x 10(9), P < .05), with a positive correlation between the amount of visceral adipose tissue (VAT) and phi2 (r = .49, P < .05); (3) S(I) is decreased in the obese group (2.8 +/- 0.3 v 9.7 +/- 1.6 10(-4) x min(-1)/microU x mL(-1)), P < .0001), with a negative correlation of S(I) with the adiposity index BMI (r = -.67, P < .0001) and VAT (r = .56, P < .05); (4) RMR, expressed in absolute terms, was significantly increased in obese versus lean subjects (5.9 +/- 0.2 v 4.6 +/- 0.3 kJ/min, P < .01), whereas when RMR was adjusted for fat-free mass (FFM), the difference between the two groups disappeared (0.09 +/- 0.003 v 0.09 +/- 0.002 kJ/min x kg FFM). We did not observe any difference in GIT between lean and obese subjects. Moreover, GIT was significantly correlated with FFM (r = .69, P < .005), but not with BMI. The amount of VAT did not correlate with RMR or GIT. In conclusion, these results suggest that in obese subjects with normal glucose tolerance, insulin sensitivity is impaired and the beta-cell hyperresponse to glucose is mainly due to an enhanced second-phase beta-cell secretion. The degree of visceral fat deposition seems to affect insulin secretion and worsens insulin sensitivity, but does not influence energy expenditure.
在肥胖症中，脂肪分布的中心型模式大多与高胰岛素血症、胰岛素抵抗及高脂血症相关，从而促进非胰岛素依赖型糖尿病和心血管疾病的发展。此外，在肥胖症中，能量消耗的变化被认为与过多体脂储存的发生或维持有关。在本研究中，通过计算机断层扫描（CT）来检测腹部脂肪分布，以研究一组糖耐量正常的肥胖受试者（n = 26；体重指数[BMI]，39±1kg/m²）和一组正常体重对照受试者（n = 9；BMI，23±1kg/m²）的内脏脂肪库、胰岛素分泌及胰岛素敏感性之间的关系。采用最小模型法，根据静脉葡萄糖耐量试验（[IVGTT]0.33g/kg体重）期间测得的血浆葡萄糖、胰岛素和C肽浓度，评估胰岛素敏感性S(I)、第一相（phi1）和第二相（phi2）β细胞敏感性。此外，我们评估了这些参数与通过间接测热法测得的静息代谢率（RMR）和葡萄糖诱导的产热（GIT）之间的关系。数据显示如下：（1）在肥胖受试者中，phi1高于对照组，但无统计学差异（252±41对157±25无量纲10⁹）；（2）肥胖受试者的phi2显著更高（27±4对14±2min⁻¹×10⁹，P<.05），内脏脂肪组织（VAT）量与phi2呈正相关（r = 0.49，P<.05）；（3）肥胖组的S(I)降低（2.8±0.3对9.7±1.610⁻⁴×min⁻¹/μU×mL⁻¹），P<.0001），S(I)与肥胖指数BMI（r = -0.67，P<.0001）和VAT（r = 0.56，P<.05）呈负相关；（4）以绝对值表示时，肥胖受试者的RMR显著高于瘦受试者（5.9±0.2对4.6±0.3kJ/min，P<.01），而当根据去脂体重（FFM）对RMR进行校正后，两组之间的差异消失（0.09±0.003对0.09±0.002kJ/min×kg FFM）。我们未观察到瘦受试者和肥胖受试者之间在GIT方面存在任何差异。此外，GIT与FFM显著相关（r = 0.69，P<.005），但与BMI无关。VAT量与RMR或GIT均无相关性。总之，这些结果表明，在糖耐量正常的肥胖受试者中，胰岛素敏感性受损，β细胞对葡萄糖的高反应性主要归因于第二相β细胞分泌增强。内脏脂肪沉积程度似乎会影响胰岛素分泌并使胰岛素敏感性恶化，但不影响能量消耗。
