MON-550 Use of the Insulin Resistance Risk Score (IRRS) to Assess Whole-Body Insulin Resistance (IR) in Children and Adolescents with Normoglycemia

Abstract Disclosure: T. Bennett-Burton: None. C.M. Rowland: Quest Diagnostics. Z. Wu: Quest Diagnostics. E.M. Bomberg: Novo Nordisk. M.J. McPhaul: Quest Diagnostics. Background: Obesity (2-18 years old: body mass index [BMI] ≥95th percentile, age-/sex-adjusted; ≥18 years old: BMI ≥30 kg/m2) prevalence has dramatically increased worldwide and affects approximately 40% of adults and 20% of youth in the U.S. Obesity is associated with the development of numerous adverse health sequelae, including IR and type 2 diabetes, in children and adults. We previously developed a method to assess whole-body IR based on fasting measurements of intact insulin and C-peptide. This tool, the IRRS, was modeled using results from insulin suppression testing in adults without diabetes. Although the IRRS has yet to be validated in youth, it has been shown to predict IR-associated clinical outcomes including hepatic steatosis in a fashion similar to its application in adults. Methods: We performed a cross-sectional study of children and adolescents (ages 9-19) with normoglycemia (normal HbA1c and fasting plasma glucose) undergoing sports participation health screenings. Demographics, anthropometrics, and fasting labs (including intact insulin and C-peptide to determine IRSS) were obtained. Participants were categorized based on BMI percentile as having underweight (UW; BMI <5th percentile), normal weight (NW; BMI 5-85th), overweight (OW; BMI 85 to <95th), and obesity (OB; BMI ≥95th). Tertiles of IRRS were estimated. Distributions of IRRS in those with normal weight versus obesity were compared by Wilcoxon rank sum test. Results: Among 76 participants (mean age: 14±2 years old; 55.3% male; 40.8% Hispanic/Latino, 38.2% non-Hispanic Black, 17.1% non-Hispanic White, 2.6% Asian, 1.3% other (61.8% NW, 25% OB, 11.8% OW, 1.3% UW), median IRRS (Q1-Q3) was 11 (7-23.8). The lowest IRRS tertile (n=28) was <7, middle tertile (n=23) was 7 to ≤19, and highest tertile (n=25) was >19. The median IRRS was statistically significantly higher among those with obesity (median: 31; range: 4-100) compared to those with normal weight (median: 10; range 2-100; p<0.01). The distribution of IRRS tertiles seen in youth are very similar to those seen in adults. Conclusions: Using the IRRS previously developed and validated in adults, in a cohort of children and adolescents with normoglycemia we found that whole-body IR was significantly higher among those with obesity compared to those with normal weight. This represents the first application of the IRRS among youth with a range of BMIs with normal hemoglobin A1c and fasting glucose levels to estimate levels of whole-body IR . Further research on use of the IRRS in youth with normoglycemia is needed, including its validation against insulin suppression testing, and its use as a marker of whole-body IR among larger and more diverse populations of children and adolescents in future cross-sectional and prospective studies. Presentation: Monday, July 14, 2025