Thomas Merlin C
Baker IDI Heart & Diabetes Institute and Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.
Adv Chronic Kidney Dis. 2014 May;21(3):311-7. doi: 10.1053/j.ackd.2014.03.004.
Diabetes continues to cast a long shadow over the lives of many people. It is now clear that even transient hyper- or hypoglycemia or increased glycemic variability around healthy mean glucose levels can have long-lasting and long-term effects on the development and progression of diabetic complications, including cardiovascular disease, kidney disease, retinopathy, and neuropathy. Even after glycemic control has been achieved and maintained for many years, it appears hard to undo the changes that are instilled, including epigenetic programming, compositional changes, post-translational modifications, or simply lead time toward an inevitable fate. This phenomenon has become known as "metabolic memory" or the "legacy effect," but it may be better characterized as "metabolic karma," in which the intent and actions of an individual (with respect to metabolic control) influence the future health of that individual. This "bad karma" has been used to explain many clinical observations surrounding diabetes and its management, including the lack of benefits in many short- and intermediate-term trials, and the potential utility of early intensive glycemic control. Further understanding the molecular basis of a metabolic legacy in diabetes will certainly provide new targets for intervention.
糖尿病继续给许多人的生活蒙上长期的阴影。现在很清楚，即使是短暂的高血糖或低血糖，或者在健康的平均血糖水平周围血糖变异性增加，都可能对糖尿病并发症（包括心血管疾病、肾脏疾病、视网膜病变和神经病变）的发生和发展产生长期影响。即使血糖控制已经实现并维持多年，似乎也很难消除已经形成的变化，包括表观遗传编程、成分变化、翻译后修饰，或者仅仅是走向不可避免命运的时间提前。这种现象被称为“代谢记忆”或“遗留效应”，但它可能更恰当地被描述为“代谢因果报应”，其中个体（关于代谢控制）的意图和行为会影响该个体未来的健康。这种“不良因果报应”已被用于解释围绕糖尿病及其管理的许多临床观察结果，包括许多短期和中期试验中缺乏益处，以及早期强化血糖控制的潜在效用。进一步了解糖尿病中代谢遗留的分子基础肯定会为干预提供新的靶点。
