Despite the fact that it is the prevalent view that insulin resistance is the main genetic factor predisposing to development of type 2 diabetes, review of several lines of evidence in the literature indicates a lack of overwhelming support for this concept. In fact, the literature better supports the case of impaired insulin secretion being the initial and main genetic factor predisposing to type 2 diabetes, especially 1) the studies in people at high risk to subsequently develop type 2 diabetes (discordant monozygotic twins and women with previous gestational diabetes), 2) the studies demonstrating compete alleviation of insulin resistance with weight loss, and 3) the studies finding that people with type 2 diabetes or IGT can have impaired insulin secretion and no insulin resistance compared with well matched NGT subjects. The fact that insulin resistance may be largely an acquired problem in no way lessens its importance in the pathogenesis of type 2 diabetes. Life style changes (exercise, weight reduction) and pharmacological agents (e.g., biguanides and thiazolidendiones) that reduce insulin resistance or increase insulin sensitivity clearly have major beneficial effects (122, 144-146, 153-155).

中文翻译：

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2型糖尿病的遗传基础：胰岛素分泌受损与胰岛素敏感性受损。

尽管普遍认为胰岛素抵抗是导致2型糖尿病发展的主要遗传因素，但对文献中几条证据的回顾表明，对该概念缺乏足够的支持。实际上，文献更好地支持了胰岛素分泌受损的情况，这是导致2型糖尿病的最初和主要遗传因素，尤其是1）在高风险人群中随后发展为2型糖尿病的研究（单卵双生双胎和患有双早糖尿病的女性）妊娠糖尿病），2）证明在减轻体重的同时可以缓解胰岛素抵抗的研究以及3）研究发现与相匹配的NGT受试者相比，患有2型糖尿病或IGT的人的胰岛素分泌受损且没有胰岛素抵抗。胰岛素抵抗在很大程度上可能是一个获得性问题，这一事实丝毫没有减弱其在2型糖尿病发病机理中的重要性。降低胰岛素抵抗或增加胰岛素敏感性的生活方式改变（锻炼，减轻体重）和药理剂（例如双胍和噻唑烷二酮）显然具有主要的有益作用（122、144-146、153-155）。