Hormonal
Obesity accelerates the loss of pancreatic beta-cell function and insulin sensitivity through ectopic adipose expansion, systemic low-grade inflammation, and lipotoxicity, leading to Type 2 Diabetes Mellitus (T2DM).
Obesity is not just about weight; it actively damages the body's ability to use insulin and produce it via inflammation and fat accumulation in organs like the liver and pancreas. Managing obesity is critical to preventing or delaying T2DM, but it requires addressing metabolic health, not just scale weight.
The ectopic expansion of adipose tissue and excessive accumulation of certain nutrients and metabolites sabotage the metabolic balance via insulin resistance, dysfunctional autophagy, and microbiome-gut-brain axis, further exacerbating the dysregulation of immunometabolism through low-grade systemic inflammation, leading to an accelerated loss of functional β-cells and gradual elevation of blood glucose.
Why this rating
This is a comprehensive review paper citing numerous GWAS, clinical studies, and mechanistic pathways, though it is not a primary RCT.
Source
Obesity and type 2 diabetes mellitus: connections in epidemiology, pathogenesis, and treatments
Rexiati Ruze et al. · Frontiers in Endocrinology · 2023
DOI 10.3389/fendo.2023.1161521
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