Type 2 diabetes across generations: from pathophysiology to prevention and management
Type 2 diabetes across generations: from pathophysiology to prevention and management
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DOI：
10.1016/s0140-6736(11)60614-4
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发表时间：
2011-07-09
期刊：
影响因子：
168.9
通讯作者：
Prentki, Marc
中科院分区：
文献类型：
--
作者：
Nolan, Christopher J.;Damm, Peter;Prentki, Marc
2型糖尿病现在是一种大流行病，而且没有减少的迹象。在这次研讨会中，我们回顾了这种疾病的病理生理学，特别关注流行病学，遗传学，表观遗传学和分子细胞生物学。有证据表明，糖尿病易感性的很大一部分是在生命早期获得的，可能是由于胎儿或新生儿通过表观遗传现象编程。因此，孕产妇和幼儿健康对于制定有效的预防战略至关重要。糖尿病的发生是由于胰岛β细胞和脂肪组织对慢性燃料过量的反应不足，这导致所谓的营养溢出，胰岛素抵抗和代谢应激。后者损害多个器官。胰岛素抵抗在迫使β细胞更加努力工作的同时，也可能对心脏等组织中与营养相关的毒性作用具有重要的防御作用。恢复卵巢功能、愈合β细胞和减少脂肪组织缺损应是治疗的优先事项。
Type 2 diabetes is now a pandemic and shows no signs of abatement. In this Seminar we review the pathophysiology of this disorder, with particular attention to epidemiology, genetics, epigenetics, and molecular cell biology. Evidence is emerging that a substantial part of diabetes susceptibility is acquired early in life, probably owing to fetal or neonatal programming via epigenetic phenomena. Maternal and early childhood health might, therefore, be crucial to the development of effective prevention strategies. Diabetes develops because of inadequate islet beta-cell and adipose-tissue responses to chronic fuel excess, which results in so-called nutrient spillover, insulin resistance, and metabolic stress. The latter damages multiple organs. Insulin resistance, while forcing beta cells to work harder, might also have an important defensive role against nutrient-related toxic effects in tissues such as the heart. Reversal of ovemutrition, healing of the beta cells, and lessening of adipose tissue defects should be treatment priorities.