{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Lobato CB"],"funding":["Fundação para a Ciência e a Tecnologia","Novo Nordisk Foundation Center for Basic Metabolic Research"],"pagination":["608248"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7793799"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["11"],"pubmed_abstract":["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 (<i>N</i>=23) in a single tertiary hospital presenting PBH symptoms (<i>Sym</i>, <i>n</i>=14) and asymptomatic weight-matched controls (<i>Asy</i>, <i>n</i>=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 <i>Sym</i> and <i>Asy</i> groups (<i>p</i>=1.000). Re-grouped according to glucose nadir during the MMTT (<i>Hypo</i> <i>n</i>=11 vs <i>NoHypo</i> <i>n</i>=12; nadir <3.05 mmol/l vs ≥3.05 mmol/l), subjects presented no differences in anthropometric (BMI: <i>p</i>=0.527) or metabolic features (HbA<sub>1c</sub>: <i>p</i>=0.358), yet distinct meal-elicited hormone dynamics were identified. Postprandial glucose excursion and peak glucose levels were similar (<i>p</i>>0.05), despite distinct late glycemic outcomes (t=60 min and t=90 min: <i>p</i><0.01), with overall greater glycemic variability in <i>Hypo</i> group (minimum-to-maximum glucose ratio: <i>p</i><0.001). <i>Hypo</i> group meal-triggered hormone profile was characterized by lower early glucagon (t=15 min: <i>p</i><0.01) and higher insulin (t=30 min: <i>p</i><0.05, t=45 min: <i>p</i><0.001), C-peptide (t=30 min: <i>p</i><0.01, t=45 min: <i>p</i><0.001, t=60 min: <i>p</i><0.05), and GLP-1 (t=45 min: <i>p</i><0.05) levels. Hyperinsulinemia was an independent risk factor for hypoglycemia (<i>p</i><0.05). After adjusting for hyperinsulinemia, early glucagon correlated with glycemic nadir (<i>p</i><0.01), and prevented postprandial hypoglycemia (<i>p</i><0.05). A higher insulin to glucagon balance in <i>Hypo</i> was observed (<i>p</i><0.05). No differences were observed in total AA, GIP or NT excursions (<i>p</i>>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."],"journal":["Frontiers in endocrinology"],"pubmed_title":["A Potential Role for Endogenous Glucagon in Preventing Post-Bariatric Hypoglycemia."],"pmcid":["PMC7793799"],"funding_grant_id":["UID/MULTI/0215/2016, UID/Multi/00215/2019, UIDB/00215/2020, UIDP/00215/2020"],"pubmed_authors":["Guimaraes M","Lobato CB","Wewer Albrechtsen NJ","Nora M","Holst JJ","Monteiro MP","Hartmann B","Hilsted L","Pereira SS"],"additional_accession":[]},"is_claimable":false,"name":"A Potential Role for Endogenous Glucagon in Preventing Post-Bariatric Hypoglycemia.","description":"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 (<i>N</i>=23) in a single tertiary hospital presenting PBH symptoms (<i>Sym</i>, <i>n</i>=14) and asymptomatic weight-matched controls (<i>Asy</i>, <i>n</i>=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 <i>Sym</i> and <i>Asy</i> groups (<i>p</i>=1.000). Re-grouped according to glucose nadir during the MMTT (<i>Hypo</i> <i>n</i>=11 vs <i>NoHypo</i> <i>n</i>=12; nadir <3.05 mmol/l vs ≥3.05 mmol/l), subjects presented no differences in anthropometric (BMI: <i>p</i>=0.527) or metabolic features (HbA<sub>1c</sub>: <i>p</i>=0.358), yet distinct meal-elicited hormone dynamics were identified. Postprandial glucose excursion and peak glucose levels were similar (<i>p</i>>0.05), despite distinct late glycemic outcomes (t=60 min and t=90 min: <i>p</i><0.01), with overall greater glycemic variability in <i>Hypo</i> group (minimum-to-maximum glucose ratio: <i>p</i><0.001). <i>Hypo</i> group meal-triggered hormone profile was characterized by lower early glucagon (t=15 min: <i>p</i><0.01) and higher insulin (t=30 min: <i>p</i><0.05, t=45 min: <i>p</i><0.001), C-peptide (t=30 min: <i>p</i><0.01, t=45 min: <i>p</i><0.001, t=60 min: <i>p</i><0.05), and GLP-1 (t=45 min: <i>p</i><0.05) levels. Hyperinsulinemia was an independent risk factor for hypoglycemia (<i>p</i><0.05). After adjusting for hyperinsulinemia, early glucagon correlated with glycemic nadir (<i>p</i><0.01), and prevented postprandial hypoglycemia (<i>p</i><0.05). A higher insulin to glucagon balance in <i>Hypo</i> was observed (<i>p</i><0.05). No differences were observed in total AA, GIP or NT excursions (<i>p</i>>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.","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020","modification":"2025-04-25T20:42:56.016Z","creation":"2025-04-06T08:29:20.901Z"},"accession":"S-EPMC7793799","cross_references":{"pubmed":["33424773"],"doi":["10.3389/fendo.2020.608248"]}}