Clin Chem Lab Med. 2014 Jan 1;52(1):69-75. doi: 10.1515/cclm-2012-0881.
In a recent article, we presented the hypothesis that decompartmentalized metal ions are a major contributor to the development of diabetic complications and supported the use of chelation therapy for the treatment of diabetic complications [Nagai R, Murray DB, Metz TO, Baynes JW. Chelation: a fundamental mechanism of action of AGE inhibitors, AGE breakers, and other inhibitors of diabetes complications. Diabetes 2012;61:549-59]. Evidence in support of this hypothesis included the observation that many drugs used in the treatment of diabetes are chelators, that advanced glycation end product (AGE) inhibitors and AGE breakers lack carbonyl-trapping or AGE-breaker activity but are potent chelators, and that simple copper chelators inhibit vascular pathology in diabetes and aging. In the present article, we extend this hypothesis, proposing the interplay between copper and iron in the development of pathology in diabetes and other chronic age-related diseases, including atherosclerosis and neurodegenerative diseases. We also discuss the need and provide a framework for the development of a clinical laboratory test to assess plasma autoxidative catalytic activity and transition metal homeostasis in vivo.
在最近的一篇文章中，我们提出了这样一个假设：去隔间化的金属离子是导致糖尿病并发症发展的主要因素，并支持使用螯合疗法来治疗糖尿病并发症[Nagai R, Murray DB, Metz TO, Baynes JW. Chelation: a fundamental mechanism of action of AGE inhibitors, AGE breakers, and other inhibitors of diabetes complications. Diabetes 2012;61:549-59]。支持这一假设的证据包括以下观察结果：许多用于治疗糖尿病的药物都是螯合剂，晚期糖基化终产物(AGE)抑制剂和 AGE 断裂剂缺乏羰基捕获或 AGE 断裂活性，但却是有效的螯合剂，而简单的铜螯合剂可抑制糖尿病和衰老中的血管病理学。在本文中，我们扩展了这一假设，提出了铜和铁在糖尿病和其他与年龄相关的慢性疾病（包括动脉粥样硬化和神经退行性疾病）发病机制中的相互作用。我们还讨论了评估体内血浆自动氧化催化活性和过渡金属动态平衡的临床实验室检测的必要性，并提供了一个框架。
