Epigenetics in Human Health and Disease Laboratory, The Alfred Medical Research and Education Precinct, Baker IDI Heart and Diabetes Institute, 5th Floor, 75 Commercial Road, Melbourne, VIC 3004, Australia.
Nat Rev Endocrinol. 2010 Dec;6(12):665-75. doi: 10.1038/nrendo.2010.188. Epub 2010 Nov 2.
Diabetes mellitus (type 1 and type 2) and the complications associated with this condition are an urgent public health problem, as the incidence of diabetes mellitus is steadily increasing. Environmental factors, such as diet and exposure to hyperglycemia, contribute to the etiology of diabetes mellitus and its associated microvascular and macrovascular complications. These vascular complications are the main cause of the morbidity and mortality burden of diabetes mellitus. The DCCT-EDIC and UKPDS epidemiological studies correlated poor glycemic control with the development of vascular complications in patients with type 1 or type 2 diabetes mellitus. The findings of these studies suggest that early exposure to hyperglycemia predisposes individuals to the development of diabetic complications, a phenomenon referred to as metabolic memory or the legacy effect. The first experimental evidence for metabolic memory was reported >20 years ago and the underlying molecular mechanisms are currently being characterized. Interestingly, transient exposure to hyperglycemia results in long-lasting epigenetic modifications that lead to changes in chromatin structure and gene expression, which mediate these persistent metabolic characteristics.
糖尿病（1 型和 2 型）及其相关并发症是一个紧迫的公共卫生问题，因为糖尿病的发病率在稳步上升。环境因素，如饮食和高血糖暴露，导致糖尿病及其相关微血管和大血管并发症的发病机制。这些血管并发症是糖尿病发病率和死亡率负担的主要原因。DCCT-EDIC 和 UKPDS 流行病学研究将血糖控制不佳与 1 型或 2 型糖尿病患者血管并发症的发展相关联。这些研究的结果表明，早期暴露于高血糖使个体易患糖尿病并发症，这种现象称为代谢记忆或遗留效应。代谢记忆的第一个实验证据是在 20 多年前报道的，目前正在对其潜在的分子机制进行描述。有趣的是，短暂的高血糖暴露会导致持久的表观遗传修饰，从而导致染色质结构和基因表达的改变，介导这些持续的代谢特征。
