MON-333 Analysis of Patients With and Without Hypoglycemia After Roux-en-Y Gastric Bypass Reveals Distinct Patterns of Postprandial Insulin Despite Similar GLP-1 Levels

Abstract H. Saeed: None. C. Cummings: None. M. Farahmandsadr: None. A. Amore: None. R. Ferraz-Bannitz: None. L. Pei: None. A.L. Sheehan: None. D.C. Simonson: Stock Owner; Self; GI Windows. M. Patti: Advisory Board Member; Self; Data and Safety Monitoring Board, Fractyl Health. Consulting Fee; Self; AstraZeneca, Hamni, MBX Biosciences. Research Investigator; Self; Dexcom. Post-bariatric hypoglycemia (PBH) can be a severe complication of bariatric surgery. We aimed to identify hormonal patterns in fasting and postprandial states distinguishing PBH vs. unaffected post-bariatric surgical individuals. Three groups of participants age 18-70, without diabetes, were recruited: control (CON, no upper GI surgery, n=11, 55% F, age 45±15 y, BMI 31±6 kg/m2), RYGB without hypoglycemia symptoms (RNonH, n=20, 100% F, age 50±10 y, BMI 35±8 kg/m2), and PBH with neuroglycopenia, unresponsive to diet and acarbose (n=20, 90% F, age 55±12 y, BMI 30±5 kg/m2). After a 12 hour fast, participants consumed a mixed meal (Ensure Compact, 64 g CHO, 18 g protein, 236 mL) containing 1000 mg acetaminophen to estimate gastric emptying. Venous glucose was measured every 10 minutes; samples collected at 0, 15, 30, 60, and 120 minutes were analyzed for GI hormones via multiplex ELISA; acetaminophen was measured by spectrophotometry (Sekisui). Data were analyzed using GraphPad Prism. Age, BMI, fasting glucose and duration post-surgery did not differ between groups. Peak postprandial glucose was significantly higher in PBH (207±39 mg/dl) and RNonH (209±29) vs. CON (158±27, p=0.0008). Nadir glucose was lower in both surgical groups and lower in PBH vs. RNonH (PBH: 55±10, RNonH 69±14, CON 86±11 mg/dl, ANOVA p<0.0001, RNonH vs. PBH p=0.003). Acetaminophen levels, reflecting gastric emptying, did not differ between surgical groups (PBH: 1.7±0.4, RNonH 1.5±0.5 mg/dl). Postprandial insulin was 60% higher in PBH vs. RNonH (p=0.001) and 3.7-fold higher than CON (p<0.0001). Likewise, postprandial C-peptide differed similarly between groups (ANOVA p<0.0001, p<0.05 for all pairwise comparisons). By contrast, peak GLP1 and peptide YY were 2-4 fold higher in both surgical groups (p<0.0001), but not different between PBH and RNonH. Pancreatic polypeptide, an indicator of cholinergic stimulation of insulin secretion, was 45% lower in surgical groups vs. CON (p<0.05), but did not differ in PBH vs. RNonH. Peak insulin, GLP1, or PP did not correlate with nadir glucose. Fasting or peak ghrelin did not differ between groups. Post-meal lactate was higher in PBH (1.7±0.5 mmol/L) and RNonH (1.5±0.3) vs. CON (1.1±0.3, p<0.0001); ratio of lactate/glucose was 32% higher in PBH vs. RNonH (p=0.0009) and 51% higher vs. CON (p<0.0001). Fasting and postprandial beta-hydroxybutyrate did not differ between groups. Compared with post RYGB participants without hypo, participants with PBH have lower nadir glucose, and higher insulin and C-peptide levels, despite similar GLP-1. This suggests additional non-GLP-1 mediated mechanisms. Higher postprandial lactate suggests the possibility of differences in hepatic glucose delivery, uptake and metabolism in PBH. Further studies will be required to identify additional meal-stimulated factors contributing to hypoglycemia in post-bariatric patients. Monday, June 3, 2024