Numata K, Tanaka K, Saito M, Shishido T, Inoue S
Third Department of Internal Medicine, Yokohama City University School of Medicine, Japan.
Int J Obes Relat Metab Disord. 1993 Feb;17(2):103-8.
To examine the cause of hyperinsulinemia in obesity, we determined plasma glucose, insulin, and C peptide responses to glucose (75g), arginine (0.5 g/kg body weight), and glucagon (1mg) in seven normal subjects and 20 obese subjects before and after weight loss by very low calorie diet therapy (Optifast, 240 kcal/day for 8 to 12 weeks). Integrated insulin and C peptide secretion in response to three different stimuli were markedly increased before weight loss and were significantly decreased following weight loss in response to glucose (mean +/- s.e. 36.6 +/- 6.4 vs. 18.4 +/- 2.6; 148.2 +/- 12.0 vs. 113.1 +/- 8.7 pmol/ml/h; P < 0.01), arginine (13.8 +/- 2.2 vs. 8.2 +/- 2.1; 94.8 +/- 11.2 vs. 66.0 +/- 6.1 pmol/ml/h; P < 0.01), and glucagon (16.5 +/- 2.7 vs. 10.7 +/- 1.5; 89.0 +/- 6.0 vs. 68.7 +/- 4.8 pmol/m/h; P < 0.01). The molar ratio of integrated C peptide to integrated insulin in response to all three stimuli was markedly decreased before, and this ratio significantly increased following weight loss (mean +/- s.e., 5.01 +/- 0.41 vs. 7.45 +/- 0.65; P < 0.01), and to arginine (7.78 +/- 0.61 vs. 10.97 +/- 1.28; P < 0.05), but not to glucagon (6.72 +/- 0.60 vs. 7.47 +/- 0.66). These findings suggest that both increased insulin secretion and decreased insulin clearance contribute to hyperinsulinemia in obese subjects. Improvement in these abnormalities to all three stimuli after weight loss also suggests that hyperinsulinemia in obesity is a consequence of the obesity itself rather than a pre-existing disorder.
为研究肥胖症患者高胰岛素血症的病因，我们测定了7名正常受试者和20名肥胖受试者在极低热量饮食疗法（Optifast，8至12周，每日240千卡）减肥前后，对葡萄糖（75克）、精氨酸（0.5克/千克体重）和胰高血糖素（1毫克）的血浆葡萄糖、胰岛素及C肽反应。减肥前，对三种不同刺激的胰岛素和C肽分泌积分显著增加，减肥后，对葡萄糖（均值±标准误：36.6±6.4对18.4±2.6；148.2±12.0对113.1±8.7皮摩尔/毫升/小时；P<0.01）、精氨酸（13.8±2.2对8.2±2.1；94.8±11.2对66.0±6.1皮摩尔/毫升/小时；P<0.01）和胰高血糖素（16.5±2.7对10.7±1.5；89.0±6.0对68.7±4.8皮摩尔/毫升/小时；P<0.01）的分泌积分显著降低。减肥前，对所有三种刺激的C肽分泌积分与胰岛素分泌积分的摩尔比显著降低，减肥后该比值显著升高（均值±标准误：5.01±0.41对7.45±0.65；P<0.01），对精氨酸的比值（7.78±0.61对10.97±1.28；P<0.05）也升高，但对胰高血糖素的比值（6.72±0.60对7.47±0.66）未升高。这些发现提示，胰岛素分泌增加和胰岛素清除率降低均导致肥胖受试者的高胰岛素血症。减肥后对所有三种刺激的这些异常情况均有改善，这也提示肥胖症中的高胰岛素血症是肥胖本身的结果，而非先前存在的疾病。
