Department of Clinical and Experimental Medicine, Section of Diabetes and Metabolic Diseases, Nuovo Ospedale Santa Chiara, Via Paradisa, 2, 56124 Pisa, Italy.
Curr Diab Rep. 2013 Jun;13(3):403-10. doi: 10.1007/s11892-013-0371-2.
Prevention of long-term complications remains the main challenge in the treatment of diabetes. A strong relationship between glucose control and development of complications is apparent in all epidemiologic studies. Yet, intervention trials have yielded questionable results, particularly when intensive treatment was introduced in patients with long-standing diabetes. It has been postulated that in these subjects, prior exposure to chronic hyperglycemia may have generated a negative "metabolic memory," preventing full exertion of the beneficial effects of any subsequent improvement of glucose control. This phenomenon has been replicated in animal models and it recognizes a molecular basis in the role of oxidative stress, advanced glycation processes, and epigenetic mechanisms accounting for self-perpetuating modifications of gene expression. Conversely, early intervention in both type 1 and type 2 diabetes has proven that good glycemic control reduces the risk of development and progression of complications with a beneficial effect that extends well beyond the duration of near-normoglycemia. This has brought up the concept of "metabolic legacy," an advantage handed down by early and effective implementation of treatments designed to reduce blood glucose levels as safely as possible along with multifactorial intervention of all cardiovascular risk factors. The evidence, nature, and clinical implication of these concepts are reviewed.
预防长期并发症仍然是糖尿病治疗的主要挑战。所有的流行病学研究都表明，血糖控制与并发症的发展之间存在着密切的关系。然而，干预试验的结果却令人怀疑，特别是当在长期患有糖尿病的患者中引入强化治疗时。有人推测，在这些患者中，先前暴露于慢性高血糖可能产生了负面的“代谢记忆”，从而阻止了随后任何改善血糖控制的有益效果的充分发挥。这一现象在动物模型中得到了复制，并在氧化应激、糖基化终产物和表观遗传机制在解释基因表达的自我持续修饰中的作用中找到了分子基础。相反，1 型和 2 型糖尿病的早期干预已经证明，良好的血糖控制可以降低并发症的发生和进展的风险，其有益效果远远超出了接近正常血糖的持续时间。这就提出了“代谢遗产”的概念，即通过尽早和有效地实施旨在尽可能安全地降低血糖水平的治疗以及对所有心血管危险因素的多因素干预，所带来的优势。本文回顾了这些概念的证据、性质和临床意义。
