Ceriello Antonio, Motz Enrico
Department of Pathology and Medicine, Experimental and Clinical, University of Udine, Italy.
Arterioscler Thromb Vasc Biol. 2004 May;24(5):816-23. doi: 10.1161/01.ATV.0000122852.22604.78. Epub 2004 Feb 19.
Type 2 diabetes is a worldwide increasing disease resulting from the interaction between a subject's genetic makeup and lifestyle. In genetically predisposed subjects, the combination of excess caloric intake and reduced physical activity induces a state of insulin resistance. When beta cells are no longer able to compensate for insulin resistance by adequately increasing insulin production, impaired glucose tolerance appears, characterized by excessive postprandial hyperglycemia. Impaired glucose tolerance may evolve into overt diabetes. These 3 conditions, ie, insulin resistance, impaired glucose tolerance, and overt diabetes, are associated with an increased risk of cardiovascular disease. Because all these conditions are also accompanied by the presence of an oxidative stress, this article proposes oxidative stress as the pathogenic mechanism linking insulin resistance with dysfunction of both beta cells and endothelium, eventually leading to overt diabetes and cardiovascular disease. This hypothesis, moreover, may also contribute to explaining why treating cardiovascular risk with drugs, such as calcium channel blockers, ACE inhibitors, AT-1 receptor antagonists, and statins, all compounds showing intracellular preventive antioxidant activity, results in the onset of new cases of diabetes possibly being reduced.
2型糖尿病是一种在全球范围内发病率不断上升的疾病，它是由个体的基因构成与生活方式之间的相互作用导致的。在具有遗传易感性的个体中，热量摄入过多与体力活动减少相结合会引发胰岛素抵抗状态。当β细胞不再能够通过充分增加胰岛素分泌来代偿胰岛素抵抗时，就会出现糖耐量受损，其特征为餐后高血糖过高。糖耐量受损可能会发展为显性糖尿病。这三种情况，即胰岛素抵抗、糖耐量受损和显性糖尿病，都与心血管疾病风险增加有关。由于所有这些情况都同时伴有氧化应激的存在，本文提出氧化应激是将胰岛素抵抗与β细胞和内皮功能障碍联系起来的致病机制，最终导致显性糖尿病和心血管疾病。此外，这一假说或许还能解释为什么使用具有细胞内预防性抗氧化活性的药物（如钙通道阻滞剂、ACE抑制剂、AT-1受体拮抗剂和他汀类药物）来治疗心血管疾病风险，可能会减少新的糖尿病病例的发生。
