{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T21:07:03Z","timestamp":1792876023368,"version":"4.5.0"},"reference-count":75,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T00:00:00Z","timestamp":1746144000000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Endocrino Diabet &amp;amp; Metabol"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Type 2 diabetes (T2D) is characterised by insulin resistance and possibly by impaired metabolic flexibility, the latter referring to the body's ability to switch between fuel sources. This review systematically examines metabolic flexibility, measured by changes in the respiratory exchange ratio (\u0394RER) during hyperinsulinaemic clamps, across lean, overweight\/obese, and T2D populations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A comprehensive search of PubMed identified 65 studies meeting the inclusion criteria, with 35 using a\u2009~40\u2009mU\/m\n                      <jats:sup>2<\/jats:sup>\n                      \/min insulin infusion rate for accurate comparisons. These studies included 985 participants: 256 lean, 497 overweight\/obese, and 232 T2D individuals. The differences in \u0394RER between the three groups were meta\u2010analysed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Basal RER values did not significantly differ across groups, but insulin\u2010stimulated \u0394RER was higher in lean individuals compared to overweight\/obese and T2D groups (\u0394RER values 0.10, 0.07 and 0.07, respectively;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.037) indicating greater metabolic flexibility in the lean group. However, high statistical heterogeneity in the \u0394RER within\u2010group results (\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      values: 92.3%\u201394.5%) suggests considerable variability among studies. A meta\u2010regression analysis accounting for age, sex, and BMI indicated that only BMI was significantly associated with \u0394RER. Factors contributing to the remaining heterogeneity likely include differences in participant characteristics (e.g., glycaemic control) and study design.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The review highlights the need for standardised data presentation in metabolic studies. Overall, metabolic flexibility appears more influenced by overweight status than T2D per se, challenging the notion of a distinct metabolic inflexibility threshold for T2D.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/edm2.70044","type":"journal-article","created":{"date-parts":[[2025,5,3]],"date-time":"2025-05-03T01:41:07Z","timestamp":1746236467000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Are Individuals With Type 2 Diabetes Metabolically Inflexible? A Systematic Review and Meta\u2010Analysis"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3197-9998","authenticated-orcid":false,"given":"Maria","family":"Hansen","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristine Kj\u00e6r","family":"Lange","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9869-0705","authenticated-orcid":false,"given":"Martin Bj\u00f8rn","family":"Stausholm","sequence":"additional","affiliation":[{"name":"Department of Physical and Occupational Therapy Copenhagen University Hospital, Bispebjerg and Frederiksberg  Copenhagen Denmark"},{"name":"Department of Global Public Health and Primary Care University of Bergen  Bergen Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9970-9535","authenticated-orcid":false,"given":"Flemming","family":"Dela","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences University of Copenhagen  Copenhagen Denmark"},{"name":"Laboratory of Sports and Nutrition Research Riga Stradins University  Riga Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,2]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)01301-6"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1999.277.6.E1130"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/obr.13131"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.2337\/db09\u20101322"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgz267"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.1032235"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2021.744187"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.49.5.677"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.2337\/db08-0043"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2017.04.015"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13679-021-00434-0"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00592-010-0245-x"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP273282"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00458.2012"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/9781119536604"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.n71"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.EJ13-0115"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-013-0025-9"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.146000"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00613.2006"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20170261"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2019.10.017"},{"key":"e_1_2_11_24_1","first-page":"338","article-title":"Changes in Glucose and Lipid Metabolism Following Weight Loss Produced by a Very Low Calorie Diet in Obese Subjects","volume":"20","author":"Bryson J. M.","year":"1996","journal-title":"International Journal of Obesity and Related Metabolic Disorders"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9378(98)70267-4"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2010-0822"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2004.03.022"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0138707"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2012-302789"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnu.2019.12.010"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00022.2022"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-979072"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1249\/MSS.0000000000000338"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ijo.0803567"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1079\/BJN19970190"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.115.122937"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00589.2003"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc20-2887"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/apha.13488"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2016-3835"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1797.2012.01662.x"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0020233"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI111060"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-3178"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/oby.20411"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/ijo.2013.10"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1409229111"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejcn.2009.32"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12986-015-0047-9"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125\u2010012\u20102482\u20108"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0051648"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1177\/1932296818805074"},{"key":"e_1_2_11_53_1","first-page":"18","article-title":"Glucose and Fat Utilization During Intravenous Administration of Glucose and Lipid Emulsion in Non\u2010Insulin\u2010Dependent Diabetic Patients","volume":"9","author":"Pelikanova T.","year":"1993","journal-title":"Nutrition"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.48.5.1082"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/ijo.2015.29"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2009.12.020"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.2147\/DMSO.S286888"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2022.01.012"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0802057105"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.2008.26717C"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0019739"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0704024104"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/oby.2004.71"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/oby.2011.290"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-019-4872-7"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-014-3328-3"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.2337\/DC11-1577"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2018-02601"},{"key":"e_1_2_11_69_1","unstructured":"International\u2010Diabetes\u2010Federation \u201cRecommendations For Managing Type 2 Diabetes In Primary Care 2017 \u201d(2017)."},{"key":"e_1_2_11_70_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-72-4-801"},{"key":"e_1_2_11_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2009.05.008"},{"key":"e_1_2_11_72_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.90558.2008"},{"key":"e_1_2_11_73_1","doi-asserted-by":"publisher","DOI":"10.2337\/diab.44.9.1010"},{"key":"e_1_2_11_74_1","doi-asserted-by":"publisher","DOI":"10.1111\/apha.13245"},{"key":"e_1_2_11_75_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-20-0619"},{"key":"e_1_2_11_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2003.12.013"}],"container-title":["Endocrinology, Diabetes &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/edm2.70044","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T07:17:21Z","timestamp":1748416641000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/edm2.70044"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5]]},"references-count":75,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,5]]}},"alternative-id":["10.1002\/edm2.70044"],"URL":"https:\/\/doi.org\/10.1002\/edm2.70044","archive":["Portico"],"relation":{},"ISSN":["2398-9238","2398-9238"],"issn-type":[{"value":"2398-9238","type":"print"},{"value":"2398-9238","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5]]},"assertion":[{"value":"2024-10-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70044"}}