Sheetz Matthew J, King George L
Lilly Research Laboratories, Indianapolis, Ind, USA.
JAMA. 2002 Nov 27;288(20):2579-88. doi: 10.1001/jama.288.20.2579.
Diabetic complications are the major cause of morbidity and mortality in persons with diabetes. Chronic hyperglycemia is a major initiator of diabetic microvascular complications (eg, retinopathy, neuropathy, nephropathy). Glucose processing uses a variety of diverse metabolic pathways; hence, chronic hyperglycemia can induce multiple cellular changes leading to complications. Several predominant well-researched theories have been proposed to explain how hyperglycemia can produce the neural and vascular derangements that are hallmarks of diabetes. These theories can be separated into those that emphasize the toxic effects of hyperglycemia and its pathophysiological derivatives (such as oxidants, hyperosmolarity, or glycation products) on tissues directly and those that ascribe pathophysiological importance to a sustained alteration in cell signaling pathways (such as changes in phospholipids or kinases) induced by the products of glucose metabolism. This article summarizes these theories and the potential therapeutic interventions that may prevent diabetic complications in the presence of hyperglycemia, control of which is often difficult with current therapeutic options.
糖尿病并发症是糖尿病患者发病和死亡的主要原因。慢性高血糖是糖尿病微血管并发症（如视网膜病变、神经病变、肾病）的主要引发因素。葡萄糖代谢采用多种不同的代谢途径；因此，慢性高血糖可引发多种细胞变化，进而导致并发症。人们提出了几种经过充分研究的主要理论来解释高血糖如何产生神经和血管紊乱，而这些紊乱是糖尿病的典型特征。这些理论可分为两类，一类强调高血糖及其病理生理衍生物（如氧化剂、高渗性或糖化产物）对组织的直接毒性作用，另一类则认为由葡萄糖代谢产物引起的细胞信号通路持续改变（如磷脂或激酶的变化）具有病理生理重要性。本文总结了这些理论以及在存在高血糖的情况下可能预防糖尿病并发症的潜在治疗干预措施，而目前的治疗选择往往难以控制高血糖。
