ESPE Yearbook of Paediatric Endocrinology

Brief Summary: This cross-sectional study in n=19 first-degree relatives of type 2 diabetes mellitus (T2DM) patients and n=19 control individuals without obesity found that while the intrinsic adipogenic potential of subcutaneous adipose tissue (SAT) is unaffected by a family history of T2DM, alterations in lysyl oxidase (LOX) mRNA expression and polyunsaturated fatty acids in triglycerides are linked to increased T2DM risk, independent of obesity. These findings suggest that SAT dysfunction, rather than its expansion capacity, may predispose individuals to T2DM.

This study challenges the prevailing notion that reduced adipogenic capacity is the primary driver of subcutaneous adipose tissue (SAT) hypertrophy in first-degree relatives of patients with type 2 diabetes mellitus (T2DM) (1, 2). Contrary to previous findings, this study indicates that the intrinsic adipogenic potential of SAT remains intact in these predisposed individuals before fat mass accumulation. Instead, the study identifies novel markers—specifically increased polyunsaturated fatty acids in triglycerides (PUFA-TAGs) and lysyl oxidase (LOX) mRNA expression—as critical factors linked to SAT dysfunction. These markers are associated with increased visceral fat, insulin resistance, and cellular stress, suggesting that they may contribute to the development of T2DM independent of traditional obesity pathways.

These findings underscore the need to explore SAT dysfunction beyond adipogenic capacity in the pathophysiology of T2DM. However, the study has some limitations, including a relatively small sample size, particularly when examining complex metabolic pathways and genetic predispositions. Additionally, the study focuses on male participants without obesity, which may limit its generalizability to other populations, including women and those with obesity.

Future research should explore these findings in larger, more diverse cohorts to validate the biomarkers identified and investigate their potential in clinical settings. Furthermore, longitudinal studies are needed to assess how these early markers of SAT dysfunction and visceral fat accumulation translate into the development of T2DM over time. The interplay between genetic predisposition, environmental factors, and adipose tissue dysfunction remains a critical area for future exploration to fully understand and mitigate the risk of T2DM.

References: 1. Arner P, Arner E, Hammarstedt A, Smith U. Genetic predisposition for type 2 diabetes, but not for overweight/obesity, is associated with a restricted adipogenesis. PLoS One. 2011;6:e18284.2. Henninger AM, Eliasson B, Jenndahl LE, Hammarstedt A. Adipocyte hypertrophy, inflammation and fibrosis characterize subcutaneous adipose tissue of healthy, non-obese subjects predisposed to type 2 diabetes. PLoS One. 2014;9:e105262.