Type 2 diabetes has long been thought to have heterogenous causes, even though epidemiological studies uniformly show a tight relationship with overnutrition. The twin cycle hypothesis postulated that interaction of self-reinforcing cycles of fat accumulation inside the liver and pancreas, driven by modest but chronic positive calorie balance, could explain the development of type 2 diabetes. This hypothesis predicted that substantial weight loss would bring about a return to the non-diabetic state, permitting observation of the pathophysiology determining the transition. These changes were postulated to reflect the basic mechanisms of causation in reverse. A series of studies over the past 15 years has elucidated these underlying mechanisms. Together with other research, the interaction of environmental and genetic factors has been clarified. This knowledge has led to successful implementation of a national programme for remission of type 2 diabetes. This Review discusses the paucity of evidence for heterogeneity in causes of type 2 diabetes and summarises the in vivo pathophysiological changes, which cause this disease of overnutrition. Type 2 diabetes has a homogenous cause expressed in genetically heterogenous individuals.

中文翻译：

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了解 2 型糖尿病的病因


尽管流行病学研究一致表明 2 型糖尿病与营养过剩有密切关系，但长期以来人们一直认为 2 型糖尿病有不同的病因。双循环假说假设，在适度但长期的正热量平衡的驱动下，肝脏和胰腺内脂肪积累的自我强化循环的相互作用可以解释 2 型糖尿病的发生。该假设预测，体重的大幅减轻将导致恢复到非糖尿病状态，从而允许观察决定转变的病理生理学。这些变化被认为反映了反向因果关系的基本机制。过去 15 年的一系列研究阐明了这些潜在机制。与其他研究一起，环境和遗传因素的相互作用已被阐明。这些知识促成了国家 2 型糖尿病缓解计划的成功实施。本综述讨论了 2 型糖尿病病因异质性证据的缺乏，并总结了导致这种营养过剩疾病的体内病理生理变化。 2 型糖尿病具有在遗传异质个体中表达的同质病因。