PMID- 33424773 OWN - NLM STAT- MEDLINE DCOM- 20210526 LR - 20210526 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 11 DP - 2020 TI - A Potential Role for Endogenous Glucagon in Preventing Post-Bariatric Hypoglycemia. PG - 608248 LID - 10.3389/fendo.2020.608248 [doi] LID - 608248 AB - Obesity and obesity-related diseases are major public health concerns that have been exponentially growing in the last decades. Bariatric surgery is an effective long-term treatment to achieve weight loss and obesity comorbidity remission. Post-bariatric hypoglycemia (PBH) is a late complication of bariatric surgery most commonly reported after Roux-en-Y gastric bypass (RYGB). PBH is the end result of postprandial hyperinsulinemia but additional endocrine mechanisms involved are still under debate. Our aim was to characterize entero-pancreatic hormone dynamics associated with postprandial hypoglycemia after RYGB. Individuals previously submitted to RYGB (N=23) in a single tertiary hospital presenting PBH symptoms (Sym, n=14) and asymptomatic weight-matched controls (Asy, n=9) were enrolled. Participants underwent a mixed-meal tolerance test (MMTT) to assess glucose, total amino acids (total AA), insulin, C-peptide, glucagon, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and neurotensin (NT). We found that hypoglycemia during the MMTT was equally frequent in Sym and Asy groups (p=1.000). Re-grouped according to glucose nadir during the MMTT (Hypo n=11 vs NoHypo n=12; nadir <3.05 mmol/l vs >/=3.05 mmol/l), subjects presented no differences in anthropometric (BMI: p=0.527) or metabolic features (HbA(1c): p=0.358), yet distinct meal-elicited hormone dynamics were identified. Postprandial glucose excursion and peak glucose levels were similar (p>0.05), despite distinct late glycemic outcomes (t=60 min and t=90 min: p<0.01), with overall greater glycemic variability in Hypo group (minimum-to-maximum glucose ratio: p<0.001). Hypo group meal-triggered hormone profile was characterized by lower early glucagon (t=15 min: p<0.01) and higher insulin (t=30 min: p<0.05, t=45 min: p<0.001), C-peptide (t=30 min: p<0.01, t=45 min: p<0.001, t=60 min: p<0.05), and GLP-1 (t=45 min: p<0.05) levels. Hyperinsulinemia was an independent risk factor for hypoglycemia (p<0.05). After adjusting for hyperinsulinemia, early glucagon correlated with glycemic nadir (p<0.01), and prevented postprandial hypoglycemia (p<0.05). A higher insulin to glucagon balance in Hypo was observed (p<0.05). No differences were observed in total AA, GIP or NT excursions (p>0.05). In sum, after RYGB, postprandial hyperinsulinemia is key in triggering PBH, but a parallel and earlier rise in endogenous glucagon might sustain the inter-individual variability in glycemic outcome beyond the effect of hyperinsulinism, advocating a potential pivotal role for glucagon in preventing hyperinsulinemic hypoglycemia. CI - Copyright (c) 2020 Lobato, Pereira, Guimaraes, Hartmann, Wewer Albrechtsen, Hilsted, Holst, Nora and Monteiro. FAU - Lobato, Carolina B AU - Lobato CB AD - Endocrine, Cardiovascular & Metabolic Research, Unit for Multidisciplinary Research in Biomedicine (UMIB), University of Porto, Porto, Portugal. AD - Department of Anatomy, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal. FAU - Pereira, Sofia S AU - Pereira SS AD - Endocrine, Cardiovascular & Metabolic Research, Unit for Multidisciplinary Research in Biomedicine (UMIB), University of Porto, Porto, Portugal. AD - Department of Anatomy, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal. AD - Instituto de Investigacao e Inovacao em Saude (I3S), Universidade do Porto, Porto, Portugal. AD - Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal. FAU - Guimaraes, Marta AU - Guimaraes M AD - Endocrine, Cardiovascular & Metabolic Research, Unit for Multidisciplinary Research in Biomedicine (UMIB), University of Porto, Porto, Portugal. AD - Department of Anatomy, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal. AD - Department of General Surgery, Centro Hospitalar de Entre o Douro e Vouga, Santa Maria da Feira, Portugal. FAU - Hartmann, Bolette AU - Hartmann B AD - Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. AD - Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Wewer Albrechtsen, Nicolai J AU - Wewer Albrechtsen NJ AD - Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. AD - Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. AD - Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. FAU - Hilsted, Linda AU - Hilsted L AD - Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. FAU - Holst, Jens J AU - Holst JJ AD - Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. AD - Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Nora, Mario AU - Nora M AD - Endocrine, Cardiovascular & Metabolic Research, Unit for Multidisciplinary Research in Biomedicine (UMIB), University of Porto, Porto, Portugal. AD - Department of General Surgery, Centro Hospitalar de Entre o Douro e Vouga, Santa Maria da Feira, Portugal. FAU - Monteiro, Mariana P AU - Monteiro MP AD - Endocrine, Cardiovascular & Metabolic Research, Unit for Multidisciplinary Research in Biomedicine (UMIB), University of Porto, Porto, Portugal. AD - Department of Anatomy, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20201130 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Amino Acids) RN - 0 (Blood Glucose) RN - 0 (Insulin) RN - 0 (Pancreatic Hormones) RN - 9007-92-5 (Glucagon) SB - IM MH - Adult MH - Amino Acids/blood/metabolism MH - *Bariatric Surgery MH - Blood Glucose/analysis MH - Body Mass Index MH - Cohort Studies MH - Female MH - Glucagon/blood/*physiology MH - Glucose Tolerance Test MH - Humans MH - Hyperinsulinism/metabolism MH - Hypoglycemia/*etiology/*prevention & control MH - Insulin/blood MH - Male MH - Middle Aged MH - Pancreatic Hormones/metabolism MH - Postoperative Complications/*prevention & control MH - Postprandial Period PMC - PMC7793799 OTO - NOTNLM OT - Roux-en-Y gastric bypass OT - glucagon OT - glucagon-like peptide-1 OT - hyperinsulinemia OT - hypoglycemia COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/01/12 06:00 MHDA- 2021/05/27 06:00 PMCR- 2020/01/01 CRDT- 2021/01/11 05:37 PHST- 2020/09/19 00:00 [received] PHST- 2020/10/22 00:00 [accepted] PHST- 2021/01/11 05:37 [entrez] PHST- 2021/01/12 06:00 [pubmed] PHST- 2021/05/27 06:00 [medline] PHST- 2020/01/01 00:00 [pmc-release] AID - 10.3389/fendo.2020.608248 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2020 Nov 30;11:608248. doi: 10.3389/fendo.2020.608248. eCollection 2020.