Metabolic abnormalities underlying the different prediabetic phenotypes in obese adolescents
Metabolic abnormalities underlying the different prediabetic phenotypes in obese adolescents
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DOI：
10.1210/jc.2007-1722
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发表时间：
2008-05-01
影响因子：
5.8
通讯作者：
Caprio, Sonia
中科院分区：
文献类型：
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作者：
Cali, Anna M. G.;Bonadonna, Riccardo C.;Caprio, Sonia
目的：本研究的目的是确定肥胖青年中孤立空腹血糖受损（IFG），孤立糖耐量受损（IGT）和IFG/IGT联合糖尿病前期状态的代谢异常。研究设计和方法：我们使用了最先进的技术（高胰岛素-血糖钳和高血糖钳），应用葡萄糖刺激胰岛素分泌模型对40例正常葡萄糖耐量（NGT）、17例IFG、23例IGT和11例IFG/IGT肥胖青少年的葡萄糖和c肽浓度进行了研究。脂肪百分比（通过双能x线吸收仪）、年龄、性别和种族在各组之间具有可比性。结果：IFG组和NGT组外周胰岛素敏感性相似。相比之下，IGT和IFG/IGT组外周胰岛素敏感性明显降低（P < 0.002）。与NGT组相比，IFG组、IGT组和IFG/IGT组的基础肝胰岛素抵抗指数（基础肝糖生成x空腹血浆胰岛素）显著升高（P < 0.009）。与NGT相比，IFG、IGT和IFG/IGT组第一阶段胰岛素分泌的葡萄糖敏感性逐渐降低。第二期分泌葡萄糖敏感性仅在IFG/IGT组有统计学意义的缺陷。在多元回归分析中，第一阶段分泌葡萄糖敏感性和基础胰岛素分泌率是FPG的显著独立预测因子（总r(2) = 25.9%）。结论：肥胖青少年的IFG主要与第一阶段胰岛素分泌的葡萄糖敏感性和肝脏胰岛素敏感性的改变有关。IGT组受到更严重程度的外周胰岛素抵抗和第一相分泌减少的影响。IFG/IGT的特点是深刻的胰岛素抵抗和第二阶段胰岛素分泌的新缺陷。
Objective: The aim of this study was to define the metabolic abnormalities underlying the prediabetic status of isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), and combined IFG/IGT in obese youth.Research Design and Methods: We used state-of-the-art techniques (hyperinsulinemic-euglycemic and hyperglycemic clamps), applying a model of glucose-stimulated insulin secretion to the glucose and C-peptide concentration, in 40 normal glucose tolerance (NGT), 17 IFG, 23 IGT, and 11 IFG/IGT obese adolescents. Percent fat (by dual-energy x-ray absorptiometry), age, gender and ethnicity were comparable among groups.Results: Peripheral insulin sensitivity was similar between the IFG and NGT groups. In contrast, the IGT and IFG/IGT groups showed marked reductions in peripheral insulin sensitivity (P < 0.002). Basal hepatic insulin resistance index (basal hepatic glucose production x fasting plasma insulin) was significantly increased in IFG, IGT, and IFG/IGT (P < 0.009) compared with NGT. Glucose sensitivity of first-phase insulin secretion was progressively lower in IFG, IGT, and IFG/IGT compared with NGT. Glucose sensitivity of second-phase secretion showed a statistically significant defect only in the IFG/IGT group. In a multivariate regression analysis, glucose sensitivity of first-phase secretion and basal insulin secretion rate were significant independent predictors of FPG (total r(2) = 25.9%).Conclusions: IFG, in obese adolescents, is linked primarily to alterations in glucose sensitivity of first-phase insulin secretion and liver insulin sensitivity. The IGT group is affected by a more severe degree of peripheral insulin resistance and reduction in first-phase secretion. IFG/IGT is hallmarked by a profound insulin resistance and by a new additional defect in second-phase insulin secretion.