Visceral adipocyte diameter was significantly associated with the risk of type 2 diabetes (OR 1.03; 95% CI 1.01-1.06), independent of overall adiposity and fat distribution.
Cross-Sectional (n=516)
Visceral, but not subcutaneous, adipocyte hypertrophy is independently associated with hyperglycemia and type 2 diabetes risk, accompanied by pro-inflammatory transcriptomic shifts.
Odds Ratio: 1.03 (95% CI 1.01–1.06)
Introduction and Objective: Although adipocyte hypertrophy is a histologic hallmark of adipose tissue dysfunction, its depot-specific contribution to systemic hyperglycemia and the underlying molecular mechanisms remain poorly defined. Methods: We analyzed paired subcutaneous and visceral adipose tissue samples from 516 adults undergoing bariatric surgery. Glucose tolerance status was classified by American Diabetes Association criteria 2025. Average adipocyte diameter was measured histologically and integrated with bulk RNA-Seq data from white adipose tissue and size-fractionated adipocytes to identify hypertrophy-driven transcriptional changes. Results: A total of 516 participants aged 32.4 (27.0-38.0) years with paired SAT and VAT samples were included, comprising 165 with normal glucose tolerance, 168 with impaired glucose tolerance, and 183 with type 2 diabetes. In multivariable Logistic regression models adjusting for overall adiposity and fat distribution, visceral adipocyte diameter was significantly associated with the risk of type 2 diabetes (OR 1.03, 95% CI 1.01-1.06), whereas subcutaneous adipocyte diameter showed no independent association (OR 1.02, 95% CI 0.99-1.04). With enlarged adipocyte size, substantial transcriptomic alterations of genes involved in glucose and lipid metabolism (e.g. fatty acid metabolism, fatty acid biosynthesis, insulin/glucagon signaling pathway, and insulin resistance) were observed. Moreover, visceral hypertrophy displayed a pro-inflammatory shift, characterized by altered abundances of dendritic cells, mast cells, mesothelium cells, and natural killer cells. Conclusion: Visceral adipocyte hypertrophy was significantly associated with hyperglycemia independent of overall adiposity and fat distribution. The current study provides a comprehensive overview of the adipocyte-hypertrophy associated transcriptomic landscape in both subcutaneous and visceral adipose tissue. Disclosure Y. Bao: None. T. Hu: None. X. Li: None. L. Yan: None. Y. Xu: None. X. Ma: None.
BAO et al. (Fri,) conducted a cross-sectional in Type 2 diabetes (n=516). Visceral adipocyte diameter was evaluated on Risk of type 2 diabetes (OR 1.03, 95% CI 1.01-1.06). Visceral adipocyte diameter was significantly associated with the risk of type 2 diabetes (OR 1.03; 95% CI 1.01-1.06), independent of overall adiposity and fat distribution.