Black Homer S
Department of Dermatology, Baylor College of Medicine, Houston, TX 77030, USA.
Antioxidants (Basel). 2022 Oct 10;11(10):2003. doi: 10.3390/antiox11102003.
The Greek physician, Aretaios, coined the term "diabetes" in the 1st Century A.D. "Mellitus" arose from the observation that the urine exhibits a sweetness due to its elevated glucose levels. Diabetes mellitus (DM) accounted for 6.7 million deaths globally in 2021 with expenditures of USD 966 billion. Mortality is predicted to rise nearly 10-fold by 2030. Oxidative stress, an imbalance between the generation and removal of reactive oxygen species (ROS), is implicated in the pathophysiology of diabetes. Whereas ROS are generated in euglycemic, natural insulin-regulated glucose metabolism, levels are regulated by factors that regulate cellular respiration, e.g., the availability of NAD-linked substrates, succinate, and oxygen; and antioxidant enzymes that maintain the cellular redox balance. Only about 1-2% of total oxygen consumption results in the formation of superoxide anion and hydrogen peroxide under normal reduced conditions. However, under hyperglycemic conditions, about 10% of the respiratory oxygen consumed may be lost as free radicals. Under hyperglycemic conditions, the two-reaction polyol pathway is activated. Nearly 30% of blood glucose can flux through this pathway-a major path contributing to NADH/NAD redox imbalance. Under these conditions, protein glycation and lipid peroxidation increase, and inflammatory cytokines are formed, leading to the further formation of ROS. As mitochondria are the major site of intracellular ROS, these organelles are subject to the deleterious effects of ROS themselves and eventually become dysfunctional-a milestone in Metabolic Syndrome (MetS) of which insulin resistance and diabetes predispose to cardiovascular disease.
公元1世纪，希腊医生阿雷泰奥斯创造了“糖尿病”这个术语。“ Mellitus”一词源于这样的观察结果，即尿液由于葡萄糖水平升高而呈现出甜味。2021年，全球糖尿病导致670万人死亡，支出达9660亿美元。预计到2030年，死亡率将上升近10倍。氧化应激，即活性氧（ROS）生成与清除之间的失衡，与糖尿病的病理生理学有关。虽然ROS在血糖正常、自然胰岛素调节的葡萄糖代谢过程中产生，但其水平受调节细胞呼吸的因素调控，例如与NAD相关的底物、琥珀酸和氧气的可用性；以及维持细胞氧化还原平衡的抗氧化酶。在正常还原条件下，只有约1-2%的总耗氧量会导致超氧阴离子和过氧化氢的形成。然而，在高血糖条件下，消耗的呼吸氧气中约有10%可能以自由基的形式损失。在高血糖条件下，双反应多元醇途径被激活。近30%的血糖可通过该途径流动，这是导致NADH/NAD氧化还原失衡的主要途径。在这些条件下，蛋白质糖基化和脂质过氧化增加，炎症细胞因子形成，导致ROS进一步形成。由于线粒体是细胞内ROS的主要产生部位，这些细胞器会受到ROS自身的有害影响，最终功能失调，这是代谢综合征（MetS）的一个里程碑，其中胰岛素抵抗和糖尿病易引发心血管疾病。
