Obesity and Type 2 Diabetes Mellitus: A Bidirectional Interplay, Pathogenic Mechanisms and Clinical Management

Cong-li Gao, Ting Zhang, Xiao-mei Wang and Song-qian Yang*

Obesity, especially central obesity, is a well-recognized major modifiable risk factor for the development of type 2 diabetes mellitus (T2DM), and the comorbidity of obesity and T2DM has become a global public health crisis with rapidly increasing prevalence. The relationship between obesity and T2DM is not a simple causal association but a complex bidirectional interplay: excessive adiposity, particularly visceral adipose tissue accumulation, triggers a cascade of metabolic and inflammatory abnormalities that lead to insulin resistance (IR) and pancreatic β-cell dysfunction, the core pathological features of T2DM; conversely, T2DM-induced metabolic disorders further exacerbate adipose tissue dysfunction, abnormal fat distribution and weight gain, forming a vicious cycle. This review systematically elaborates the bidirectional pathological link between obesity and T2DM, clarifies the key underlying mechanisms including chronic low-grade inflammation, adipose tissue dysfunction, gut micro biota dysbiosis, mitochondrial dysfunction and genetic epigenetic regulation. We further summarize the current clinical strategies for the comprehensive management of obesity-related T2DM, covering lifestyle intervention, pharmacotherapy and bariatric surgery, and prospect the emerging research directions such as targeted therapy for adipose tissue inflammation, gut micro biota modulation and precision medicine. This review aims to provide a comprehensive understanding of the intimate association between obesity and T2DM, and offer a reference for the optimized clinical management and novel therapeutic development for patients with obesity and T2DM comorbidity.

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Published on: Mar 31, 2026 Pages: 5-16

Full Text PDF Full Text HTML DOI: 10.17352/gjodms.000070
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