{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T06:18:26Z","timestamp":1788157106604,"version":"build-2803163510"},"reference-count":22,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o Para a Ci\u00eancia e Tecnologia","award":["UIDB\/00215\/2020"],"award-info":[{"award-number":["UIDB\/00215\/2020"]}]},{"name":"Funda\u00e7\u00e3o Para a Ci\u00eancia e Tecnologia","award":["UIDP\/00215\/2020"],"award-info":[{"award-number":["UIDP\/00215\/2020"]}]},{"name":"Funda\u00e7\u00e3o Para a Ci\u00eancia e Tecnologia","award":["LA\/P\/0064\/2020"],"award-info":[{"award-number":["LA\/P\/0064\/2020"]}]},{"award":["UIDB\/00215\/2020"],"award-info":[{"award-number":["UIDB\/00215\/2020"]}],"id":[{"id":"https:\/\/ror.org\/00snfqn58","id-type":"ROR","asserted-by":"publisher"}]},{"award":["UIDP\/00215\/2020"],"award-info":[{"award-number":["UIDP\/00215\/2020"]}],"id":[{"id":"https:\/\/ror.org\/00snfqn58","id-type":"ROR","asserted-by":"publisher"}]},{"award":["LA\/P\/0064\/2020"],"award-info":[{"award-number":["LA\/P\/0064\/2020"]}],"id":[{"id":"https:\/\/ror.org\/00snfqn58","id-type":"ROR","asserted-by":"publisher"}]},{"name":"FCT\/MCTES","award":["10.54499\/UIDB\/04585\/2020"],"award-info":[{"award-number":["10.54499\/UIDB\/04585\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Pers. Med.","JPM"],"abstract":"<jats:p>Introduction: Refeeding syndrome (RS) is a life-threatening metabolic complication of nutritional support. Prolonged fasting, frequently observed in malnourished patients referred for percutaneous endoscopic gastrostomy (PEG), may induce histological and ultrastructural changes in the intestinal mucosa, potentially influencing metabolic adaptation during nutritional reintroduction. Mixed-Meal Tolerance Tests (MMTT) combined with targeted metabolic profiling allow dynamic assessment of serum glucose, gastrointestinal hormones and metabolites, which may help to elucidate the metabolic adaptations associated with fasting and refeeding. Objective: The present study aims to perform MMTT in PEG patients to characterize enteroendocrine hormone responses and metabolomic profiles following a prolonged period of reduced nutritional intake and subsequent enteral refeeding. Methods: This prospective, single-center study includes adults referred for PEG after at least one month of oral intake below 50% of energy needs. The MMTT will be performed at PEG placement and after 3\u20136 months of enteral nutrition. Serial blood samples will be collected from baseline up to 120 minutes post-meal to measure serum glucose, insulin, C-peptide, electrolytes and gastrointestinal hormones (GLP-1, GIP, ghrelin and PYY), and for targeted metabolomic profiling by spectroscopy. Clinical and nutritional data will be prospectively recorded. Exploratory analyses will assess metabolic and hormonal changes over time and their potential associations with relevant clinical characteristics. The study was approved by the institutional ethics committee, and patient informed consent will be obtained. Conclusion: This study integrates MMTT and targeted metabolomic profiling to characterize hormonal and metabolic responses during fasting and refeeding in PEG patients considered at increased risk of RS due to prolonged markedly reduced oral intake. The findings may improve understanding of metabolic adaptations associated with nutritional reintroduction and may identify candidate hormonal and metabolic signatures to support future studies on RS pathophysiology and risk assessment.<\/jats:p>","DOI":"10.3390\/jpm16090452","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T05:55:56Z","timestamp":1788155756000},"page":"452","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Combined Assessment of Gastrointestinal Hormones and Metabolomic Profiling Following Mixed-Meal Tolerance Tests in Patients at Increased Risk of Refeeding Syndrome: Study Protocol"],"prefix":"10.3390","volume":"16","author":[{"given":"Gon\u00e7alo","family":"Nunes","sequence":"first","affiliation":[{"name":"Gastroenterology Department, GENE\u2014Artificial Feeding Team, Unidade Local de Sa\u00fade Almada-Seixal, Hospital Garcia de Orta, 2805-267 Almada, Portugal"},{"name":"ICBAS-UP\u2014School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal"},{"name":"Aging Lab, Egas Moniz Center for Interdisciplinary Research (CiiEM), Egas Moniz School of Health & Science, 2829-511 Almada, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8094-7197","authenticated-orcid":false,"given":"Marta","family":"Guimar\u00e3es","sequence":"additional","affiliation":[{"name":"Department of Endocrine and Metabolic Research in Biomedicine, ICBAS\u2014School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal"},{"name":"ITR\u2014Laboratory of Integrative and Translational Research in Population Health, Rua das Taipas 135, 4050-600 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6947-4560","authenticated-orcid":false,"given":"Sofia S.","family":"Pereira","sequence":"additional","affiliation":[{"name":"Department of Endocrine and Metabolic Research in Biomedicine, ICBAS\u2014School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal"},{"name":"ITR\u2014Laboratory of Integrative and Translational Research in Population Health, Rua das Taipas 135, 4050-600 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1068-379X","authenticated-orcid":false,"given":"Ivo","family":"Mendes","sequence":"additional","affiliation":[{"name":"Gastroenterology Department, GENE\u2014Artificial Feeding Team, Unidade Local de Sa\u00fade Almada-Seixal, Hospital Garcia de Orta, 2805-267 Almada, Portugal"},{"name":"Aging Lab, Egas Moniz Center for Interdisciplinary Research (CiiEM), Egas Moniz School of Health & Science, 2829-511 Almada, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Vara-Luiz","sequence":"additional","affiliation":[{"name":"Gastroenterology Department, GENE\u2014Artificial Feeding Team, Unidade Local de Sa\u00fade Almada-Seixal, Hospital Garcia de Orta, 2805-267 Almada, Portugal"},{"name":"Aging Lab, Egas Moniz Center for Interdisciplinary Research (CiiEM), Egas Moniz School of Health & Science, 2829-511 Almada, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e1tia","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Gastroenterology Department, GENE\u2014Artificial Feeding Team, Unidade Local de Sa\u00fade Almada-Seixal, Hospital Garcia de Orta, 2805-267 Almada, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9158-5861","authenticated-orcid":false,"given":"Marta","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Gastroenterology Department, GENE\u2014Artificial Feeding Team, Unidade Local de Sa\u00fade Almada-Seixal, Hospital Garcia de Orta, 2805-267 Almada, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patr\u00edcia","family":"Mendes","sequence":"additional","affiliation":[{"name":"Clinical Pathology Department, Clinical Chemistry Laboratory, Unidade Local de Sa\u00fade Almada-Seixal, Hospital Garcia de Orta, 2805-267 Almada, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rute","family":"Santos","sequence":"additional","affiliation":[{"name":"Clinical Pathology Department, Clinical Chemistry Laboratory, Unidade Local de Sa\u00fade Almada-Seixal, Hospital Garcia de Orta, 2805-267 Almada, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T\u00e2nia","family":"Meira","sequence":"additional","affiliation":[{"name":"Gastroenterology Department, GENE\u2014Artificial Feeding Team, Unidade Local de Sa\u00fade Almada-Seixal, Hospital Garcia de Orta, 2805-267 Almada, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Fonseca","sequence":"additional","affiliation":[{"name":"Gastroenterology Department, GENE\u2014Artificial Feeding Team, Unidade Local de Sa\u00fade Almada-Seixal, Hospital Garcia de Orta, 2805-267 Almada, Portugal"},{"name":"ICBAS-UP\u2014School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal"},{"name":"Aging Lab, Egas Moniz Center for Interdisciplinary Research (CiiEM), Egas Moniz School of Health & Science, 2829-511 Almada, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1097\/MEG.0000000000001202","article-title":"Refeeding syndrome in the gastroenterology practice: How concerned should we be?","volume":"30","author":"Nunes","year":"2018","journal-title":"Eur. 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