Murea Mariana, Ma Lijun, Freedman Barry I
Department of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
Rev Diabet Stud. 2012 Spring;9(1):6-22. doi: 10.1900/RDS.2012.9.6. Epub 2012 May 10.
Faced with a global epidemic of type 2 diabetes (T2D), it is critical that researchers improve our understanding of the pathogenesis of T2D and related vascular complications. These findings may ultimately lead to novel treatment options for disease prevention or delaying progression. Two major paradigms jointly underlie the development of T2D and related coronary artery disease, diabetic nephropathy, and diabetic retinopathy. These paradigms include the genetic risk variants and behavioral/environmental factors. This article systematically reviews the literature supporting genetic determinants in the pathogenesis of T2D and diabetic vasculopathy, and the functional implications of these gene variants on the regulation of beta-cell function and glucose homeostasis. We update the discovery of diabetes and diabetic vasculopathy risk variants, and describe the genetic technologies that have uncovered them. Also, genomic linkage between obesity and T2D is discussed. There is a complementary role for behavioral and environmental factors modulating the genetic susceptibility and diabetes risk. Epidemiological and clinical data demonstrating the effects of behavioral and novel environmental exposures on disease expression are reviewed. Finally, a succinct overview of recent landmark clinical trials addressing glycemic control and its impact on rates of vascular complications is presented. It is expected that novel strategies to exploit the gene- and exposure-related underpinnings of T2D will soon result.
面对2型糖尿病（T2D）的全球流行，研究人员加深对T2D发病机制及相关血管并发症的理解至关重要。这些发现最终可能带来预防疾病或延缓疾病进展的新治疗选择。两个主要范式共同构成了T2D及相关冠状动脉疾病、糖尿病肾病和糖尿病视网膜病变发展的基础。这些范式包括遗传风险变异和行为/环境因素。本文系统回顾了支持T2D发病机制及糖尿病血管病变中遗传决定因素的文献，以及这些基因变异对β细胞功能调节和葡萄糖稳态的功能影响。我们更新了糖尿病和糖尿病血管病变风险变异的发现，并描述了揭示这些变异的遗传技术。此外，还讨论了肥胖与T2D之间的基因组连锁关系。行为和环境因素在调节遗传易感性和糖尿病风险方面具有互补作用。本文回顾了证明行为和新型环境暴露对疾病表现影响的流行病学和临床数据。最后，简要概述了近期针对血糖控制及其对血管并发症发生率影响的具有里程碑意义的临床试验。预计不久将产生利用T2D基因和暴露相关基础的新策略。
