{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T21:16:55Z","timestamp":1772399815514,"version":"3.50.1"},"reference-count":48,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T00:00:00Z","timestamp":1690416000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["FCT\/UIDB\/00617\/2020 (CIAFEL)"],"award-info":[{"award-number":["FCT\/UIDB\/00617\/2020 (CIAFEL)"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["LA\/P\/0064\/2020 (ITR)"],"award-info":[{"award-number":["LA\/P\/0064\/2020 (ITR)"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["SFRH\/BD 2020.06520 (FCNAUP)"],"award-info":[{"award-number":["SFRH\/BD 2020.06520 (FCNAUP)"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Nutr Health"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:p> Background: Cardiovascular disease is the leading cause of mortality associated with diabetes, which is characterized by chronic hyperglycemia. Low-carbohydrate diet has gained popularity as an intervention in patients with type 2 diabetes mellitus, acting to improve glycemic profile and serum lipids. In its turn, exercise in hypoxia induces specific adaptations, mostly modulated via hypoxia-induced transcription factor signaling cascade, which increases with exposure to altitude, and promotes angiogenesis, glycogen supply, glucose tolerance, and raises GLUT-4 expression. Aim: Given that hyperglycemia decreases HIF-1\u03b1 and it is better controlled when following a low-carbohydrate diet, this study aims to examine the hypothesis that a combination of both low-carbohydrate diet and chronic exercise in hypoxia in type 2 diabetes mellitus is associated with improved glycemic control and cardiovascular parameters, whose protocol is described. Methods: Patients with type 2 diabetes mellitus ( n\u2009=\u200948) will be recruited and randomized into one of the three groups: (a) Control group: Control diet (low-fat and moderate-carbohydrate diet)\u2009+\u2009exercise in normoxia; (2) exercise in hypoxia group: Control diet\u2009+\u2009exercise in hypoxia; (3) intervention group: Low-carbohydrate diet (low-carbohydrate and high-fat diet)\u2009+\u2009exercise in hypoxia. Before and after 8 weeks of interventions, cardiopulmonary tests (Bruce protocol), body composition and blood pressure will be evaluated. Blood samples will be collected to measure hypoxia-induced transcription factor, C-reactive protein, glycemic and lipid profiles. Summary: This will be the first trial to examine the isolated and combined effect of chronic exercise in hypoxia and low-carbohydrate diet in type 2 diabetes mellitus. This trial will help to fill a significant research gap, guide future research and contribute to the combined nutrition and exercise approach to type 2 diabetes mellitus. <\/jats:p>","DOI":"10.1177\/02601060231190663","type":"journal-article","created":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T20:09:07Z","timestamp":1690488547000},"page":"5-13","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":4,"title":["Combined low-carbohydrate diet and long-term exercise in hypoxia in type 2 diabetes: A randomized controlled trial protocol to assess glycemic control, cardiovascular risk factors and body composition"],"prefix":"10.1177","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2720-0603","authenticated-orcid":false,"given":"Raquel","family":"Kindlovits","sequence":"first","affiliation":[{"name":"Faculty of Nutrition and Food Sciences, University of Porto, FCNAUP, Porto, Portugal"}]},{"given":"Ana C","family":"Sousa","sequence":"additional","affiliation":[{"name":"Research Center in Sports Sciences, Health Sciences and Human Development, CIDESD, University of Maia, Maia, Portugal"}]},{"given":"Jo\u00e3o L","family":"Viana","sequence":"additional","affiliation":[{"name":"Research Center in Sports Sciences, Health Sciences and Human Development, CIDESD, University of Maia, Maia, Portugal"}]},{"given":"Jaime","family":"Milheiro","sequence":"additional","affiliation":[{"name":"CMEP, Exercise Medical Center, Porto, Portugal"}]},{"given":"Franklim","family":"Marques","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, FFUP, Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9286-4716","authenticated-orcid":false,"given":"Vitor H","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Faculty of Nutrition and Food Sciences, University of Porto, FCNAUP, Porto, Portugal"},{"name":"Research Center in Physical Activity, Health and Leisure, CIAFEL \u2013 Faculty of Sports, University of Porto, FADEUP, Portugal"},{"name":"Laboratory for Integrative and Translational Research in Population Health, ITR, Porto, Portugal"}]}],"member":"179","published-online":{"date-parts":[[2023,7,27]]},"reference":[{"key":"bibr1-02601060231190663","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.2007.121558"},{"issue":"1","key":"bibr2-02601060231190663","volume":"23","author":"American Diabetes A","year":"2000","journal-title":"Diabetes Care"},{"key":"bibr3-02601060231190663","doi-asserted-by":"publisher","DOI":"10.2337\/dc16-0614"},{"key":"bibr4-02601060231190663","doi-asserted-by":"publisher","DOI":"10.1001\/jama.286.10.1218"},{"key":"bibr5-02601060231190663","doi-asserted-by":"publisher","DOI":"10.1136\/bjsports-2020-102955"},{"key":"bibr6-02601060231190663","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2003.07.021"},{"key":"bibr7-02601060231190663","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.e7586"},{"key":"bibr8-02601060231190663","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnu.2020.11.027"},{"key":"bibr9-02601060231190663","doi-asserted-by":"publisher","DOI":"10.2337\/dc16-1728"},{"key":"bibr10-02601060231190663","doi-asserted-by":"publisher","DOI":"10.2337\/dc08-2108"},{"key":"bibr11-02601060231190663","doi-asserted-by":"publisher","DOI":"10.1007\/BF00374176"},{"key":"bibr12-02601060231190663","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2009.01151.x"},{"key":"bibr13-02601060231190663","doi-asserted-by":"publisher","DOI":"10.2337\/dci19-0014"},{"key":"bibr14-02601060231190663","doi-asserted-by":"publisher","DOI":"10.15171\/jcvtr.2016.05"},{"key":"bibr15-02601060231190663","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00318.2020"},{"key":"bibr16-02601060231190663","volume":"372","author":"Goldenberg JZ","year":"2021","journal-title":"BMJ"},{"key":"bibr17-02601060231190663","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0b013e32832c0018"},{"key":"bibr18-02601060231190663","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-018-4628-9"},{"issue":"8","key":"bibr19-02601060231190663","first-page":"673","volume":"6","author":"Joslin EP","year":"1916","journal-title":"Canadian Medical Association Journal"},{"key":"bibr20-02601060231190663","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2022.02.046"},{"key":"bibr21-02601060231190663","doi-asserted-by":"publisher","DOI":"10.1089\/ham.2022.0029"},{"key":"bibr22-02601060231190663","doi-asserted-by":"publisher","DOI":"10.1016\/j.jada.2007.10.003"},{"issue":"5","key":"bibr23-02601060231190663","first-page":"1138","volume":"63","author":"Krishnamachary B","year":"2003","journal-title":"Cancer Research"},{"key":"bibr24-02601060231190663","doi-asserted-by":"publisher","DOI":"10.1139\/y2012-138"},{"key":"bibr25-02601060231190663","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5868-8-115"},{"key":"bibr26-02601060231190663","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2018.12.022"},{"key":"bibr27-02601060231190663","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-009-0146-8"},{"key":"bibr28-02601060231190663","doi-asserted-by":"publisher","DOI":"10.1101\/gad.12.2.149"},{"key":"bibr29-02601060231190663","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8227(01)00368-0"},{"key":"bibr30-02601060231190663","volume-title":"High Altitude Oxygenation","author":"Mathew TM","year":"2022"},{"key":"bibr31-02601060231190663","doi-asserted-by":"publisher","DOI":"10.1111\/dme.13862"},{"key":"bibr32-02601060231190663","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2016.00224"},{"key":"bibr33-02601060231190663","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2004.01.008"},{"key":"bibr34-02601060231190663","doi-asserted-by":"publisher","DOI":"10.1001\/jama.285.15.1987"},{"key":"bibr35-02601060231190663","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa011858"},{"key":"bibr36-02601060231190663","doi-asserted-by":"publisher","DOI":"10.4324\/9781315385662"},{"key":"bibr37-02601060231190663","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2021.109118"},{"key":"bibr38-02601060231190663","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-08-040006"},{"key":"bibr39-02601060231190663","doi-asserted-by":"publisher","DOI":"10.4158\/EP.13.S1.1"},{"key":"bibr40-02601060231190663","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2018.02.026"},{"key":"bibr41-02601060231190663","doi-asserted-by":"publisher","DOI":"10.1007\/s00592-020-01568-8"},{"key":"bibr42-02601060231190663","doi-asserted-by":"publisher","DOI":"10.1136\/bmjdrc-2016-000354"},{"key":"bibr43-02601060231190663","doi-asserted-by":"publisher","DOI":"10.1007\/s11948-000-0025-z"},{"key":"bibr44-02601060231190663","doi-asserted-by":"publisher","DOI":"10.4161\/cc.9.1.10371"},{"key":"bibr45-02601060231190663","doi-asserted-by":"publisher","DOI":"10.1007\/s13105-011-0115-1"},{"key":"bibr46-02601060231190663","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/nqy096"},{"key":"bibr47-02601060231190663","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.281053"},{"key":"bibr48-02601060231190663","doi-asserted-by":"publisher","DOI":"10.2337\/dc19-0532"}],"container-title":["Nutrition and Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/02601060231190663","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/02601060231190663","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/02601060231190663","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T05:34:16Z","timestamp":1740807256000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/02601060231190663"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,27]]},"references-count":48,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,4]]}},"alternative-id":["10.1177\/02601060231190663"],"URL":"https:\/\/doi.org\/10.1177\/02601060231190663","relation":{},"ISSN":["0260-1060","2047-945X"],"issn-type":[{"value":"0260-1060","type":"print"},{"value":"2047-945X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,27]]}}}