The accelerator hypothesis: weight gain as the missing link between Type I and Type II diabetes
The accelerator hypothesis: weight gain as the missing link between Type I and Type II diabetes
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DOI：
10.1007/s001250100548
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发表时间：
2001-07-01
期刊：
影响因子：
8.2
通讯作者：
Wilkin, TJ
中科院分区：
文献类型：
--
作者：
Wilkin, TJ
血糖浓度由包含两个组件的环路控制，即分泌胰岛素的β细胞和对其做出反应的胰岛素敏感组织（肝脏、肌肉、脂肪）。血糖失控可能是由于β细胞无法分泌胰岛素、组织对其作用产生抵抗或两者兼而有之。 I 型（胰岛素依赖型）和 II 型（非胰岛素依赖型）糖尿病之间的区别在临床和病因学上都变得越来越模糊，β 细胞功能不全是其共同特征。 “加速器假说”确定了三个不同程度地加速细胞凋亡导致的β细胞损失的过程；体质、胰岛素抵抗和自身免疫。没有一种加速剂会导致糖尿病而不导致体重过度增加，“加速剂假说”认为这种趋势是工业发达国家两种类型糖尿病发病率上升的核心。体重增加会导致胰岛素抵抗增加，从而导致血糖控制减弱。血糖升高（糖毒性）会直接加速所有β细胞凋亡，并通过诱导β细胞免疫原，进一步加速遗传上易患自身免疫的亚群的凋亡。 “加速器假说”设想的是两种类型的糖尿病之间存在重叠，而不是重叠。体重是所有糖尿病发生和发病率上升的核心。只有节奏才能区分“类型”。控制体重增加以及随之而来的胰岛素抵抗可能是最大限度地减少这两者的方法。
Blood glucose concentrations are controlled by a loop incorporating two components, the beta cells which secrete insulin and the insulin-sensitive tissues (liver, muscle, adipose) which respond to it. Loss of blood glucose control might result from failure of the beta cells to secrete insulin, resistance of the tissues to its action, or a combination of both. The distinctions between Type I (insulin-dependent) and Type II (non-insulin-dependent) diabetes mellitus are becoming increasingly blurred both clinically and aetiologically, where beta-cell insufficiency is the shared characteristic. The 'Accelerator Hypothesis' identifies three processes which variably accelerate the loss of beta cells through apoptosis; constitution, insulin resistance and autoimmunity. None of the accelerators leads to diabetes without excess weight gain, a trend which the 'Accelerator Hypothesis' deems central to the rising incidence of both types of diabetes in the industrially developed world. Weight gain causes an increase in insulin resistance, which results in the weakening of glucose control. The rising blood glucose (glucotoxicity) accelerates beta-cell apoptosis directly in all and, by inducing beta-cell immunogens, further accelerates it in a subset genetically predisposed to autoimmunity. Rather than overlap between two types of diabetes, the 'Accelerator Hypothesis' envisages overlay. Body mass is central to the development and rising incidence of all diabetes. Only tempo distinguishes the 'types'. The control of weight gain, and with it insulin resistance, could be the means of minimising both.