Endocrine Abstracts

JOINT3311

Background: Oxyntomodulin (OXM), an endogenous peptide derived from preproglucagon, plays a crucial role in energy homeostasis by modulating appetite regulation and glucose metabolism through dual activation of the glucagon-like peptide-1 receptor (GLP-1R) and glucagon receptor (GCGR). Despite its known anorexigenic and metabolic effects, its role in obesity pathophysiology remains underexplored. The present study investigates OXM dynamics in obesity and its potential utility as a biomarker for metabolic dysfunction and obesity-related risk stratification.

Methods: A total of 261 participants were stratified into three groups based on body mass index (BMI): normal-weight controls (CG, n = 39), overweight individuals (O1, n = 88), and obese individuals (O2, n = 134). Comprehensive metabolic profiling was conducted, including an oral glucose tolerance test (OGTT), insulin and C-peptide levels, body composition analysis via DXA/BIA, and serum OXM quantification using enzyme-linked immunosorbent assay (ELISA). Correlation analyses assessed associations between OXM levels and key metabolic parameters.

Results: Serum OXM levels significantly differed across groups (p < 0.0001, ANOVA). The obese group (O2) exhibited significantly higher OXM levels compared to both the overweight (O1, p < 0.0001) and control (CG, p < 0.0001) groups. While a trend toward increased OXM was observed in overweight individuals (01) compared to controls (CG), this difference did not reach statistical significance (P = 0.2258). In the obese cohort, OXM levels correlated positively with fasting insulin (r = 0.52, p < 0.0001), C-peptide (r = 0.60, p < 0.0001), and visceral adipose tissue (r = 0.33, p < 0.0001), suggesting an adaptive response to metabolic stress. However, the increase in OXM was not associated with improved glycemic control, as indicated by a weak positive correlation with HbA1c (r = 0.25, P = 0.0049).

Conclusion: The findings support the hypothesis that elevated OXM in obesity represents a compensatory response to metabolic dysregulation rather than an effective homeostatic mechanism. The significant differences in OXM between groups, along with its correlation with key metabolic indicators, suggest its potential as a screening biomarker for obesity-related metabolic risk. Further research is warranted to evaluate its predictive value in clinical settings and its potential utility in personalized therapeutic strategies, particularly in the context of OXM-based pharmacotherapies.