Monti L D, Brambilla P, Stefani I, Caumo A, Magni F, Poma R, Tomasini L, Agostini G, Galli-Kienle M, Cobelli C
Istituto Scientifico H. San Raffaele, Cattedra di Clinica Medica, Università di Milano, Italy.
Diabetologia. 1995 Jun;38(6):739-47. doi: 10.1007/BF00401849.
To evaluate the early metabolic alterations induced by obesity, we studied glucose turnover and lipid levels in obese children with fasting normoinsulinaemia. Two experimental protocols were carried out. Protocol I consisted of a euglycaemic glucose clamp at two rates of insulin infusion. Protocol II was similar to protocol I except for a variable lipid infusion used to maintain basal non-esterified fatty acid (NEFA) levels. During protocol I, the glucose disappearance rates were lower in obese children, while no differences were found in hepatic glucose release. NEFA response to insulin was not substantially altered in obese children either at low or high insulin infusion. During protocol II, the NEFA clamp induced a 25% reduction in peripheral insulin sensitivity in control children whereas no changes were observed in obese children. Interestingly, lipid infusion in control children was not sufficient to reproduce the same degree of insulin resistance observed in obese children, suggesting that NEFA are only one of the determinants of insulin resistance at this stage of obesity. In conclusion, the present study provides a portrait of glucose metabolism and lipid levels in normoinsulinaemic obese children. Our results document that peripheral insulin resistance is the first alteration at this stage of obesity, whereas an increase in insulin secretion and a defect in the inhibition of hepatic glucose release by insulin may develop at a later stage. In addition, primarily receptor and post-receptor defects and some alterations of NEFA metabolism are likely to coexist in the induction of insulin resistance at this stage of obesity.
为评估肥胖引起的早期代谢改变，我们研究了空腹正常胰岛素血症肥胖儿童的葡萄糖周转率和血脂水平。进行了两个实验方案。方案I包括以两种胰岛素输注速率进行的正常血糖葡萄糖钳夹。方案II与方案I相似，不同之处在于使用可变脂质输注来维持基础非酯化脂肪酸（NEFA）水平。在方案I期间，肥胖儿童的葡萄糖消失率较低，而肝葡萄糖释放未发现差异。无论胰岛素输注量低或高，肥胖儿童对胰岛素的NEFA反应均未发生实质性改变。在方案II期间，NEFA钳夹使对照儿童的外周胰岛素敏感性降低了25%，而肥胖儿童未观察到变化。有趣的是，对照儿童的脂质输注不足以重现肥胖儿童中观察到的相同程度的胰岛素抵抗，这表明在肥胖的这个阶段，NEFA只是胰岛素抵抗的决定因素之一。总之，本研究描绘了正常胰岛素血症肥胖儿童的葡萄糖代谢和血脂水平。我们的结果表明，外周胰岛素抵抗是肥胖这个阶段的第一个改变，而胰岛素分泌增加和胰岛素对肝葡萄糖释放抑制的缺陷可能在后期出现。此外，在肥胖的这个阶段，胰岛素抵抗的诱导可能主要存在受体和受体后缺陷以及NEFA代谢的一些改变。
