2型糖尿病的自然病程与遗传学研究进展

2型糖尿病的自然病程反映了在控制血糖的稳态中起重要作用的胰岛素敏感性和胰岛β-细胞分泌胰岛素的功能之间的关系。当两者之间能够达到平衡时,血糖可保持正常;而一旦两者之间的平衡被打破,血糖即开始升高并继而发展为糖尿病。大多数2型糖尿病是因为胰岛素抵抗和β-细胞功能缺陷两方面病因共同造成的。目前已有比较充分的证据表明,2型糖尿病是一种由多种遗传和环境因素所导致的复杂遗传病。在过去的20年间,人们已经发现了许多与胰岛素抵抗和β-细胞缺陷相关的糖尿病基因,但这些基因的突变只能解释很少一部分2型糖尿病患者的病因学,而与大多数2型糖尿病患者相关的糖尿病基因尚未被发现。

Nature history and genetics of type 2 diabetes

The nature history of type 2 diabetes is characterized by the interaction between beta-cells function and insulin sensitivity. Normal glucose tolerance could be maintained when there is a balance between insulin sensitivity and beta-cells function. For most of type 2 diabetic patients, both defects in insulin secretion as well as insulin action are needed for the development of diabetes. In addition, there is abundant evidence indicating the importance of genetic factors in the development of type 2 diabetes, including data from the twin studies, family studies, studies among different ethnic groups living in the same environment and admixture studies. In the last two decades, that genetic defects affecting both beta-cells function and insulin sensitivity has been identified. But those defects can only explain a very small portion of etiology of type 2 diabetes, and the gene defects contributing to the cause of most type 2 diabetes are still at large. We have learned, from the past experience that type 2 diabetes is a very heterogeneous and complex disease. The complexity of type 2 diabetes is related to factors such as genetic heterogeneity, interactions between genes, and the modulating role played by the environment.