376-P: Analysis of the Fasting and Postprandial Plasma Metabolome Reveals Metabolic Signatures of Postbariatric Hypoglycemia

Abstract

One severe complication of gastrointestinal and bariatric surgery is post-bariatric hypoglycemia (PBH). Affected patients may develop severe hypoglycemia, typically 1-3 hours after meals. While exaggerated postprandial incretin hormone and insulin secretion has been implicated, additional contributors to hypoglycemia remain uncertain. We performed untargeted semiquantitative metabolomic analysis of plasma samples collected in the fasting state and at 30 and 120 minutes after a liquid mixed meal (Ensure) in 13 individuals with PBH post-RYGB, 10 asymptomatic post-RYGB, and 8 overweight/obese individuals without history of gastrointestinal surgery. Multiple analytes were reduced in the fasting state in PBH, including 10 amino acids (Leu, Ile, Val, Ala, Phe, Tyr, Met, Trp, Thr, Asn, nominal p<0.05 vs. asymptomatic, FC -1.2 to -1.4), multiple lipid species (C22:6 LPC, C22:6 LPE, C20:4 LPE, C56:7 TAG, C54:5 TAG, C50:5 TAG, p<0.05 vs. asymptomatic,FC -1.3 to -1.5). We also observed robust reduction (2-10 fold, p<0.05) in multiple tryptophan pathway metabolites, including kynurenic acid, xanthurenate, and serotonin. Markers of insulin resistance and T2D risk, such as 2-aminoadipate and alpha-hydroxybutyrate, and multiple B complex vitamins (B3, B5, B6) were also decreased in PBH in the fasting state. By contrast, tricarboxylic acid (TCA) cycle intermediates such as aconitate, isocitrate, succinate and malate and the ketone beta-hydroxybutyrate were all increased in PBH (p<0.05). In summary, we identify several metabolic signatures of PBH including reduction in multiple circulating AA, lipid species, and tryptophan intermediates as well as increased TCA cycle intermediates. Together these could potentially contribute to alterations in glucose metabolic flux in both the fasting and postprandial state in individuals with PBH. Disclosure R. Ferraz-Bannitz: None. C.M. Mulla: None. J. Dreyfuss: None. H. Pan: None. M. Patti: Consultant; Self; Fractyl Laboratories, Inc. Research Support; Self; Dexcom, Inc., Xeris Pharmaceuticals, Inc. Other Relationship; Self; Academy of Nutrition and Dietetics, American Diabetes Association, American Society of Metabolic and Bariatric Surgery, Endocrine Society, Insulet Corporation, King Abdullah International Medical Research Center, SUNY Downstate. Funding National Institutes of Health (R01DK121995, P30DK046200)