Accurate assessment of β-cell function -: The hyperbolic correction
Accurate assessment of β-cell function -: The hyperbolic correction
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DOI：
10.2337/diabetes.51.2007.s212
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发表时间：
2002-02-01
期刊：
影响因子：
7.7
通讯作者：
Van Citters, G
中科院分区：
文献类型：
--
作者：
Bergman, RN;Ader, M;Van Citters, G
只有在过去的十年中，模型研究预测，并敲除实验证实，2型糖尿病是一种“2-hit”疾病，其中胰岛素抵抗必然伴随着β细胞缺陷，阻止胰岛素分泌的代偿性上调。这种长期延迟的洞察力与一个常数的发展有关，即“处置指数”，将β细胞敏感性-分泌关系描述为矩形双曲线。胰岛素敏感性的变化伴随着β细胞对葡萄糖敏感性的代偿性改变。胰岛素敏感的受试者不需要对外源性葡萄糖产生大量胰岛素应答来维持正常血糖。但是，如果她们的胰岛素敏感性下降了80%，就像在怀孕后期一样，她们需要5倍的胰岛素反应才能达到相同的倾向指数。妊娠期糖尿病患者的胰岛素反应与正常志愿者相似;乍一看，这表明类似的胰岛功能，但处置指数的效用是将这种反应正常化为妊娠晚期胰岛素抵抗的幅度，揭示严重的β细胞缺乏。该指数是一个定量的，方便的，准确的工具，在分析流行病学数据和识别早期糖耐量受损。然而，独立的主要问题仍然存在：胰岛素抵抗的原因，2型糖尿病中β细胞补偿不足的原因，以及来自胰岛素抵抗组织的信号的性质，这些信号未能引起对葡萄糖和其他刺激的敏感性的适当β细胞增加。处置指数可能仍然是最准确的生理措施，用于测试假设和解决方案，这些挑战在整个生物体。糖尿病51（补编1）：S212-5220，2002年。
Only in the last decade did modeling studies predict, and knockout experiments confirm, that type 2 diabetes is a "2-hit" disease in which insulin resistance is necessarily accompanied by beta-cell defect(s) preventing the compensatory upregulation of insulin secretion. This long-delayed insight was associated with the development of a constant, the "disposition index," describing the beta-cell sensitivity-secretion relationship as a rectangular hyperbola. Shifts in insulin sensitivity are accompanied by compensatory alterations in beta-cell sensitivity to glucose. Insulin-sensitive subjects do not require a massive insulin response to exogenous glucose to maintain a normal blood glucose. But if their insulin sensitivity decreases by 80%, as in late pregnancy, they need a fivefold greater insulin response to achieve an identical disposition index. Women with gestational diabetes have an insulin response similar to that of normal volunteers; at first glance, this suggests similar islet function, but the utility of the disposition index is to normalize this response to the amplitude of third trimester insulin resistance, revealing severe beta-cell deficiency. The index is a quantitative, convenient, and accurate tool in analyzing epidemiologic data and identifying incipient impaired glucose tolerance. Separate major issues remain, however: the causes of insulin resistance, the causes of the failure of adequate beta-cell compensation in type 2 diabetes, and the nature of the signal(s) from insulin-resistant tissues that fail to elicit the appropriate beta-cell increment in sensitivity to glucose and other stimuli. The disposition index is likely to remain the most accurate physiologic measure for testing hypotheses and solutions to these challenges in whole organisms. Diabetes 51 (Suppl. 1):S212-5220, 2002.