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We examined glucose metabolism and metabolomics profiles after 12 h and 36 h fasting in non-obese and obese participants and people with type 2 diabetes using oral glucose tolerance (OGTT) and intravenous glucose tolerance testing (IVGTT). Insulin sensitivity was estimated by established indices and mass spectrometric metabolomics was performed on fasting serum samples. Participants had a mean age of 43 \u00b1 16 years (62% women). Fasting levels of glucose, insulin and C-peptide were significantly lower in all cohorts after 36 h compared to 12 h fasting (p &lt; 0.05). In non-obese participants, glucose levels were significantly higher after 36 h compared to 12 h fasting at 120 min of OGTT (109 \u00b1 31 mg\/dL vs. 79 \u00b1 18 mg\/dL; p = 0.001) but insulin levels were lower after 36 h of fasting at 30 min of OGTT (41.2 \u00b1 34.1 mU\/L after 36 h vs. 56.1 \u00b1 29.7 mU\/L; p &lt; 0.05). In contrast, no significant differences were observed in obese participants or people with diabetes. Insulin sensitivity improved in all cohorts after 36 h fasting. In line, metabolomics revealed subtle baseline differences and an attenuated metabolic response to fasting in obese participants and people with diabetes. Our data demonstrate an improved insulin sensitivity after 36 h of fasting with higher glucose variations and reduced early insulin response in non-obese people only.<\/jats:p>","DOI":"10.3390\/nu15030511","type":"journal-article","created":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T04:19:40Z","timestamp":1674101980000},"page":"511","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Glucose Metabolism and Metabolomic Changes in Response to Prolonged Fasting in Individuals with Obesity, Type 2 Diabetes and Non-Obese People\u2014A Cohort Trial"],"prefix":"10.3390","volume":"15","author":[{"given":"Norbert J.","family":"Tripolt","sequence":"first","affiliation":[{"name":"Interdisciplinary Metabolic Medicine Trials Unit, Division of Endocrinology and Diabetology, Medical University of Graz, 8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0756-0014","authenticated-orcid":false,"given":"Sebastian J.","family":"Hofer","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biosciences, NAWI Graz, University of Graz, Humboldtstra\u00dfe 50, 8010 Graz, Austria"},{"name":"BioTechMed Graz, 8010 Graz, Austria"},{"name":"Field of Excellence BioHealth, University of Graz, 8010 Graz, Austria"},{"name":"Inserm U1138, Equipe Labellis\u00e9e par la Ligue Contre le Cancer, Centre de Recherche des Cordeliers, Institut Universitaire de France, Sorbonne Universit\u00e9, Universit\u00e9 de Paris, 75006 Paris, France"},{"name":"Metabolomics and Cell Biology Platforms, Institut Gustave Roussy, 94805 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter N.","family":"Pferschy","sequence":"additional","affiliation":[{"name":"Interdisciplinary Metabolic Medicine Trials Unit, Division of Endocrinology and Diabetology, Medical University of Graz, 8010 Graz, Austria"},{"name":"Center for Biomarker Research in Medicine (CBmed), 8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faisal","family":"Aziz","sequence":"additional","affiliation":[{"name":"Interdisciplinary Metabolic Medicine Trials Unit, Division of Endocrinology and Diabetology, Medical University of Graz, 8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylv\u00e8re","family":"Durand","sequence":"additional","affiliation":[{"name":"Inserm U1138, Equipe Labellis\u00e9e par la Ligue Contre le Cancer, Centre de Recherche des Cordeliers, Institut Universitaire de France, Sorbonne Universit\u00e9, Universit\u00e9 de Paris, 75006 Paris, France"},{"name":"Metabolomics and Cell Biology Platforms, Institut Gustave Roussy, 94805 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanny","family":"Aprahamian","sequence":"additional","affiliation":[{"name":"Inserm U1138, Equipe Labellis\u00e9e par la Ligue Contre le Cancer, Centre de Recherche des Cordeliers, Institut Universitaire de France, Sorbonne Universit\u00e9, Universit\u00e9 de Paris, 75006 Paris, France"},{"name":"Metabolomics and Cell Biology Platforms, Institut Gustave Roussy, 94805 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nitharsshini","family":"Nirmalathasan","sequence":"additional","affiliation":[{"name":"Inserm U1138, Equipe Labellis\u00e9e par la Ligue Contre le Cancer, Centre de Recherche des Cordeliers, Institut Universitaire de France, Sorbonne Universit\u00e9, Universit\u00e9 de Paris, 75006 Paris, France"},{"name":"Metabolomics and Cell Biology Platforms, Institut Gustave Roussy, 94805 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7541-8338","authenticated-orcid":false,"given":"Mara","family":"Waltenstorfer","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biosciences, NAWI Graz, University of Graz, Humboldtstra\u00dfe 50, 8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3559-1130","authenticated-orcid":false,"given":"Tobias","family":"Eisenberg","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biosciences, NAWI Graz, University of Graz, Humboldtstra\u00dfe 50, 8010 Graz, Austria"},{"name":"BioTechMed Graz, 8010 Graz, Austria"},{"name":"Field of Excellence BioHealth, University of Graz, 8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna M. 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