8396 Growth Hormone Secretion after Glucagon Stimulation is Increased in Individuals with History of Bariatric Surgery

Abstract

Abstract Disclosure: L. Pei: None. C. Cummings: None. H. Saeed: None. M. Farahmandsadr: None. A. Amore: None. A. Sheehan: None. R. Ferraz-Bannitz: None. D.C. Simonson: Stock Owner; Self; GI Windows. Other; Self; wife owns Phase V Technologies. M. Patti: Advisory Board Member; Self; data and safety monitoring board on Fractyl Health. Consulting Fee; Self; AstraZeneca, Hamni, MBX Biosciences. Grant Recipient; Self; Receive investigator-initiated research funding from Dexcom. Background: Growth hormone (GH) is an important counterregulatory hormone and regulator of hepatic glucose metabolism. Previous studies demonstrated increased plasma GH and reduced plasma growth hormone receptor (GHR) after bariatric surgery in both rodents and humans. Moreover, plasma GHR was identified as mediator of improved glycemic control after Roux-en-Y gastric bypass (RYGB). We now test the hypothesis that altered GH and/or GHR levels contribute to post-bariatric hypoglycemia (PBH). Methods: Cross-sectional studies were performed at a single academic institution. GH secretion was assessed after 1mg IV glucagon (GCG) and during hyperinsulinemic-hypoglycemic clamp in 3 groups: 1) post-RYGB without hypoglycemia symptoms (RnonH) (20F, age 51±11 (mean±SD) y, BMI 35±8 kg/m2, HbA1c 5.2±0.3%, 10.6±5.3 years post-surgery), 2) PBH (18F/2M, age 54±12y, BMI 30.5±4.6 kg/m2, HbA1c 5.2±0.3%, 9.4±6.0 years post-surgery), 3) weight-similar controls without upper GI surgery (CON) (6F/4M, age 47.1±13.1y, BMI 31.9±5.7 kg/m2, HbA1c 5.4±0.3%). Plasma GHR and GH were measured via ELISA. Results: Fasting GH did not differ between groups (mean±SE, CON: 285±78, RnonH: 860±179, PBH: 980±284 pg/mL, P=0.16). Peak incremental glucose response to GCG, ranging from 46-59 mg/dL, did not differ between groups. At 120 min after GCG, GH was significantly higher in both PBH and RnonH vs. CON (PBH: 3018±678, RnonH: 2521±656, CON: 481±137 pg/mL, ANOVA P= 0.012, PBH vs. CON P=0.003, RnonH vs. CON P=0.02). Peak GH in PBH was significantly higher vs. CON (3431± 655 vs. 547±153 pg/mL, P=0.03), but did not differ in RnonH vs. PBH. Peak GH was inversely correlated with postoperative duration in PBH only (r=-0.49, P=0.03), with BMI in both surgical groups (PBH: r=-0.49, P=0.03, RnonH: r=-0.57, P=0.009) and with percent body fat (impedance plethysmography) in the combined surgical group (r=-0.51, P=0.0007). In contrast, GH during hyperinsulinemic hypoglycemia did not differ between groups (CON: 9660 ±2588, RnonH: 7759±1751, PBH: 7309±1549 pg/mL, P=0.3) at similar degrees of hypoglycemia (CON: 54.8±1.5, RnonH: 50.7±1.0, PBH: 50.9±1.4 mg/dL). Fasting plasma GHR did not differ (CON: 23.3±3.8, RnonH: 19.4±2.8, PBH: 13.8±2.1 ng/mL, P=0.10). GHR was correlated with percent fat mass in the combined surgical group (r=0.56, P=0.0003) but not in CON. Conclusion: Plasma GH did not differ as a function of prior RYGB, with or without hypoglycemia, in the fasting state or in response to insulin-induced hypoglycemia. However, GCG-stimulated GH levels were 5-6-fold higher in individuals with history of RYGB, numerically higher in PBH, and inversely related to body fat and postop duration. Together these results suggest that reduced GH is not likely driving hypoglycemia in PBH, but that alterations in glucagon-mediated GH secretion and/or action may contribute to observed metabolic effects of RYGB. Presentation: 6/1/2024