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将肥胖与2型糖尿病联系起来的内分泌和代谢机制:对靶向治疗的启示。

Endocrine and Metabolic Mechanisms Linking Obesity to Type 2 Diabetes: Implications for Targeted Therapy.

作者信息

Allocca Salvatore, Monda Antonietta, Messina Antonietta, Casillo Maria, Sapuppo Walter, Monda Vincenzo, Polito Rita, Di Maio Girolamo, Monda Marcellino, La Marra Marco

机构信息

Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy.

Department of Human Science and Quality of Life Promotion, San Raffaele Telematic University, 00166 Rome, Italy.

出版信息

Healthcare (Basel). 2025 Jun 16;13(12):1437. doi: 10.3390/healthcare13121437.

Abstract

Obesity and Type 2 Diabetes Mellitus (T2DM) are interrelated chronic conditions whose global prevalence continues to rise, posing significant clinical and socioeconomic challenges. Their pathophysiological intersection-commonly referred to as "diabesity"-is sustained by a complex interplay of mechanisms, including visceral adipose tissue inflammation, macrophage polarization, disrupted insulin signaling, and adipokine imbalance. These processes contribute to chronic low-grade systemic inflammation, impair pancreatic β-cell function, and exacerbate glucose intolerance. This review critically explores the mechanistic connections between obesity and T2DM, with a focus on recent advances in pharmacological therapies-such as GLP-1 receptor agonists, SGLT2 inhibitors, and dual GIP/GLP-1 receptor agonists-alongside evidence-based lifestyle modifications and bariatric procedures. By integrating current translational and clinical findings, we aim to provide a comprehensive perspective to support the development of more effective and individualized treatment strategies for diabesity.

摘要

肥胖症和2型糖尿病(T2DM)是相互关联的慢性疾病,其全球患病率持续上升,带来了重大的临床和社会经济挑战。它们在病理生理上的交叉点——通常被称为“糖尿病肥胖症”——由多种机制的复杂相互作用维持,包括内脏脂肪组织炎症、巨噬细胞极化、胰岛素信号传导中断和脂肪因子失衡。这些过程导致慢性低度全身炎症,损害胰腺β细胞功能,并加剧葡萄糖不耐受。本综述批判性地探讨了肥胖症和T2DM之间的机制联系,重点关注药物治疗的最新进展,如胰高血糖素样肽-1(GLP-1)受体激动剂、钠-葡萄糖协同转运蛋白2(SGLT2)抑制剂和双重葡萄糖依赖性促胰岛素多肽(GIP)/GLP-1受体激动剂,以及基于证据的生活方式改变和减肥手术。通过整合当前的转化研究和临床发现,我们旨在提供一个全面的视角,以支持为糖尿病肥胖症制定更有效和个性化的治疗策略。

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