Department of Endocrinology and Metabolism, Section of Metabolic Diseases and Diabetes, University of Pisa, Pisa, Italy.
Diabet Med. 2009 Dec;26(12):1185-92. doi: 10.1111/j.1464-5491.2009.02847.x.
Type 2 diabetes mellitus is a disease characterized by persistent and progressive deterioration of glucose tolerance. Both insulin resistance and impaired insulin secretion contribute to development of Type 2 diabetes. However, whilst insulin resistance is fully apparent in the pre-diabetic condition, impairment of insulin secretion worsens over the time, being paralleled by a progressive decline in both pancreatic B-cell function and B-cell mass. Intense research has identified a number of genetic variants that may predispose to impaired B-cell function, but such predisposition can be precipitated and worsened by toxic effects of hyperglycaemia (glucotoxicity) and elevated levels of free fatty acids (lipotoxicity). All these aspects of the pathogenesis of Type 2 diabetes are discussed in this review. Moreover, treatments that target reduction in glucotoxicity or lipotoxicity are outlined, including emerging strategies that target the role of glucagon-like peptide 1 and sodium glucose co-transporter 2.
2 型糖尿病是一种以葡萄糖耐量持续和进行性恶化为特征的疾病。胰岛素抵抗和胰岛素分泌受损均有助于 2 型糖尿病的发生。然而，虽然在糖尿病前期就已经完全出现胰岛素抵抗，但随着时间的推移，胰岛素分泌受损会恶化，同时胰腺β细胞功能和β细胞数量也会逐渐下降。大量研究已经确定了一些可能导致β细胞功能受损的遗传变异，但高血糖（糖毒性）和游离脂肪酸水平升高（脂毒性）的毒性作用会促使和加重这种易感性。本综述讨论了 2 型糖尿病发病机制的所有这些方面。此外，还概述了针对降低糖毒性或脂毒性的治疗方法，包括针对胰高血糖素样肽 1 和钠-葡萄糖共转运蛋白 2 作用的新兴策略。
