Enhanced oral glucose tolerance test for early detection of insulin resistance and metabolic complications in children with obesity

Background and aims: Early detection of insulin resistance (IR) and obesity-related complications is crucial for preventing type 2 diabetes. This study aimed to identify dynamic metabolic biomarkers for more precise early detection of IR and metabolic abnormalities. Methods: This cross-sectional cohort study evaluated IR and metabolic biomarkers in 403 children with obesity (median age 13.18 years, 51.3 % female, 98.5 % with obesity) using an enhanced oral glucose tolerance test (eOGTT). IR was assessed via four indices, with the Matsuda Insulin Sensitivity Index (ISI-M) used as the primary measure. Participants were stratified into quartiles based on ISI-M. Results: Participants with the highest IR (Q1) were older (p = 0.002), had a higher body mass index, were in a more advanced pubertal stage (p < 0.001), and had significantly elevated glucose and insulin levels (p < 0.001 for both) compared to the most insulin sensitive (Q4), with significant differences observed across all quartiles (p <0.050 for all). Insulin at 120 min demonstrated excellent diagnostic accuracy for IR (AUC=0.958). Triglyceride levels in Q1 showed minimal decline during the eOGTT, while greater declines were observed with increasing insulin sensitivity (p = 0.002 across quartiles), suggesting that a lack of decline in triglycerides may help identify IR. High-sensitivity C-reactive protein levels increased with IR (p = 0.024). Baseline beta-hydroxybutyrate levels were highest in the Q4 and showed the greatest absolute decrease during the eOGTT, compared to Q1 (p < 0.001 for both). Conclusions: We validated established IR markers in children with obesity, while demonstrating that eOGTT may offer improved characterization and earlier identification of those at risk for metabolic complications.