5124 Increased Copeptin May Reflect Vasopressin-Related Metabolic Changes After Bariatric Surgery

Abstract Disclosure: F. Galbiati: None. A. Aulinas Maso: None. I. Becetti: None. M. Lauze: None. V. Singhal: None. E.A. Lawson: Research Investigator; Self; received research funding and study drug from Tonix Pharmaceuticals. M. Bredella: None. M. Bredella: None. M. Misra: Advisory Board Member; Self; key opinion leader for Lumos Pharma. Consulting Fee; Self; Up To Date, Receives royalties. Objective: Vasopressin (AVP) is a neurohormone that decreases fat mass, promotes muscle regeneration, improves glucose homeostasis, and protects against hypoglycemia in animals and humans. Copeptin, a stable cleavage product of AVP, is positively associated with body mass index (BMI), insulin resistance, and metabolic syndrome in adults, suggesting an adaptive increase in AVP to counteract metabolic disruption. Similarly, copeptin was positively correlated with BMI in children. Metabolic and bariatric surgery (MBS) is highly effective at reducing metabolic complications of obesity, and underlying mechanisms may provide insights into novel therapeutics for obesity management. No study has investigated copeptin pre- and post-MBS in humans. We hypothesized that after MBS, (1) copeptin would increase and (2) increased copeptin would be associated with improved metabolic parameters. Methods: Longitudinal study in 64 adolescents and young adults (78% females; age [mean±SD] 18.7±2.8 years) with obesity (BMI 45.6±6.8 kg/m2). 34 underwent MBS (sleeve gastrectomy or Roux-en-Y gastric bypass) and 30 underwent non-surgical (NS) lifestyle management. We measured fasting circulating copeptin, %fat, and lean mass by dual-energy X-ray absorptiometry, hemoglobin A1c (HbA1c), and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) at baseline and 12 months. Results: Groups were similar for age, sex, race, and pubertal stage. Baseline BMI and %fat were higher in MBS (p≤.012). Baseline copeptin, %lean mass, HbA1c, and HOMA-IR did not differ across groups (p≥.103). MBS vs NS 12-month changes were [median(IQR)]: BMI -29.0 (-33.7, -16.5)% and 0.54 (-3.10, +4.37)%; %fat -8.03 (-13.33, -4.25) and -0.68 (-2.92, 0.64); %lean mass 7.73 (3.45, 12.38) and 0.83 (-.58, 2.73); HbA1c -0.40 (-0.52, -0.20) and -0.10 (-0.20, -0.02); HOMA-IR (mean±SD) -2.47±2.17 and 0.76±2.42 (ps≤.001). Baseline copeptin was correlated negatively with %fat (rho=-.25; p=.045), and positively with %lean mass (trend-level rho=.25, p=0.051). Copeptin increased in the MBS group and decreased in the NS group (time-x;-treatment effect: p=.017). Overall, copeptin change was correlated negatively with %fat change (rho=-.29; p=.025) and positively with %lean mass change (trend-level rho=0.24, p=.070). Copeptin change was positively correlated with changes in %lean mass (rho=.37, p=.045), HbA1c (rho=.46; p=.010), and HOMA-IR (rho=.53; p=.004), only after MBS. Conclusion: Overall, increase in copeptin over 12 months was associated with improved body composition, suggesting that increased AVP following MBS may contribute to its associated metabolic improvements. However, within the MBS group, improved glucose homeostasis was associated with reductions in copeptin, suggesting a possible protective mechanism against post-bariatric hypoglycemia. Presentation: 6/2/2024