Department of Endocrinology, Canberra Hospital and Australian National University Medical School, Canberra, ACT, Australia.
Lancet. 2011 Jul 9;378(9786):169-81. doi: 10.1016/S0140-6736(11)60614-4. Epub 2011 Jun 24.
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 β-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 β cells to work harder, might also have an important defensive role against nutrient-related toxic effects in tissues such as the heart. Reversal of overnutrition, healing of the β cells, and lessening of adipose tissue defects should be treatment priorities.
2 型糖尿病现在是一种全球性的流行病，没有减弱的迹象。在本次研讨会上，我们将回顾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，糖尿病的易感性有相当一部分是在生命早期获得的，这可能是由于胎儿或新生儿通过表观遗传现象进行编程。因此，母体和儿童早期健康对制定有效的预防策略可能至关重要。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剩的反应不足，导致所谓的营养溢出、胰岛素抵抗和代谢应激。后者会损害多个器官。尽管胰岛素抵抗迫使β细胞更加努力地工作，但它在抵抗心脏等组织中与营养相关的毒性作用方面可能也具有重要的防御作用。逆转营养过剩、修复β细胞和减少脂肪组织缺陷应成为治疗的重点。
