Sex differences in regional adipose tissue depots pose different threats for the development of Type 2 diabetes in males and females

Summary Type 2 diabetes mellitus (T2DM) affects males and females disproportionately. In midlife, more males have T2DM than females. The sex difference in T2DM prevalence is, in part, explained by differences in regional adipose tissue characteristics. With obesity, changes to regional adipokine and cytokine release increases the risk of T2DM in both males and females with males having greater levels of TNFα and females having greater levels of leptin, CRP, and adiponectin. Regional immune cell infiltration appears to be pathogenic in both sexes via different routes as males with obesity have greater VAT ATM and a decrease in the protective Treg cells, whereas females have greater SAT ATM and T cells. Lastly, the ability of female adipose tissue to expand all regions through hyperplasia, rather than hypertrophy, protects them against the development of large insulin‐resistant adipocytes that dominate male adipose tissue. The objective of this review is to discuss how sex may affect regional differences in adipose tissue characteristics and how these differences may distinguish the development of T2DM in males and females. In doing so, we will show that the origins of T2DM development differ between males and females.