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2型糖尿病:发病机制与基因诊断

Type 2 diabetes mellitus: pathogenesis and genetic diagnosis.

作者信息

Himanshu D, Ali Wahid, Wamique Mohd

机构信息

Department of Endocrinology, King George's Medical University, Lucknow, Uttar Pradesh 226003 India.

Department of Pathology, King George's Medical University, Lucknow, Uttar Pradesh 226003 India.

出版信息

J Diabetes Metab Disord. 2020 Sep 22;19(2):1959-1966. doi: 10.1007/s40200-020-00641-x. eCollection 2020 Dec.

Abstract

Type 2 diabetes mellitus (T2DM) is a heterogeneous condition that is related to both defective insulin secretion and peripheral insulin resistance. Beta cells are the major organ for secreting insulin hence, it is important to maintain an adequate beta-cell mass in response to various changes. Insulin resistance is a major cause of T2DM leads to elevated free fatty acid (FFA) levels which increases beta-cell mass and insulin secretion to compensate for insulin insensitivity. Chronic increase of plasma FFA levels results in disturbances in lipid metabolism, which contributes to decreased beta-cell function and lipotoxicity thus promoting T2DM. In the present review, we have discussed the process of beta-cell destruction, the role of genes in contributing to the fast increase in the progression of T2DM in detail. More than 130 variants in various T2DM susceptibility and candidate genes have been discovered to be associated with T2DM. Still, these variants elucidate only a small amount of total heritability of T2DM. Further, there is also an inventory of presently used therapeutic tools and a review of novel therapeutic approaches like incretin-based therapies or sodium-glucose transporter-2 inhibitors. Additionally, providing a concise but comprehensive update, this review will be essential to every clinician involved in the treatment of diabetes mellitus.

摘要

2型糖尿病(T2DM)是一种异质性疾病,与胰岛素分泌缺陷和外周胰岛素抵抗均有关。β细胞是分泌胰岛素的主要器官,因此,应对各种变化维持足够的β细胞量很重要。胰岛素抵抗是T2DM的主要病因,会导致游离脂肪酸(FFA)水平升高,进而增加β细胞量和胰岛素分泌以补偿胰岛素不敏感性。血浆FFA水平的长期升高会导致脂质代谢紊乱,这会导致β细胞功能下降和脂毒性,从而促进T2DM的发生。在本综述中,我们详细讨论了β细胞破坏的过程以及基因在T2DM进展快速增加中所起的作用。已发现各种T2DM易感性和候选基因中的130多个变异与T2DM相关。然而,这些变异仅阐明了T2DM总遗传力的一小部分。此外,本文还介绍了目前使用的治疗工具,并综述了新型治疗方法,如基于肠促胰岛素的疗法或钠-葡萄糖协同转运蛋白2抑制剂。此外,本综述提供了简洁而全面的更新内容,对每位参与糖尿病治疗的临床医生都至关重要。

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