A REVIEW ON ETIOPATHOGENESIS OF TYPE 2 DIABETES MELLITUS

Type 2 Diabetes Mellitus (T2DM) is a hyperglycemic syndrome with several characteristic features. It continues to rise unabatedly in all pockets of the world, parallels with affluence and can be controlled but not cured. It has a definite involvement of genetic component but environmental factors play overwhelmingly dominant role in etiopathogenesis. Insulin resistance (IR) and obesity are singular instigators of T2DM. Hyperglycemia induces OS through multiple routes : a)stimulated polyol pathway where in ≤ 30% glucose can be diverted to sorbitol and fructose, b)increased transcription of genes for proinflammatory cytokines and plasminogen activator inhibitor-1 (PAI-1) c) activation of protein kinase-C (PKC) leading to several molecular changes d)increased synthesis of Advanced Glycation End Products (AGEs) e)changes in a receptor far AGEs and f) autooxidation of glucose with formation of ketoimines and AGEs. All these processes are accompanied with alteration in redox status, Reactive Oxygen Species (ROS), Reactive Nitrogen Species (RNS) and Oxidative Stress (OS) which trigger T2DM and its complications. Initial hurriedly planned and executed experimental and clinical studies showed promising results of antioxidant therapies, but recent studies indicate that excess intake/ supplement may have adverse outcomes including increased mortality. It is advocated that antioxidants should be given only if preexisting deficiency is present. Selection of antioxidant is another important aspect. Lastly but most importantly the impact of OS is not obligatory but facultative. As such only those diabetic patients will be benefited by antioxidant therapies that have impelling punch of prooxidants.