{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T14:56:39Z","timestamp":1777560999104,"version":"3.51.4"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Type 2 diabetes mellitus (T2DM) induces integrated cardiovascular and metabolic impairments. The comprehensive effect of aerobic exercise on these systemic alterations remains unclear. Therefore, we designed a randomized controlled trial to investigate its impact on integrated cardiovascular health \u2014 specifically assessed by nitroglycerin-mediated dilation (NMD) and myocardial global work efficiency (GWE) \u2014 and systemic energy metabolism in patients with T2DM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This study is a randomized, single-assessor-blind, parallel-group, two-arm controlled trial that will enroll 74 patients with T2DM. Participants will be randomly assigned in a 1:1 ratio to either a 12-week supervised aerobic exercise group (55\u201375% of HR\n                      <jats:sub>peak<\/jats:sub>\n                      , three times per week) or a non-exercise control group. The primary outcomes are the changes from baseline to 12 weeks in NMD and GWE. Secondary outcomes include key cardiometabolic indicators (energy metabolism, insulin levels), office and 24-hour ambulatory blood pressure, cardiovascular risk factors, 24-hour movement behavior, cardiopulmonary function, arterial stiffness (baPWV), vascular endothelial function (FMD), cardiac electrical activity, echocardiographic parameters, and self-reported fatigue. Additional exploratory variables include markers of myocardial injury and skeletal muscle injury, circulating markers of oxidative stress and inflammation, central fatigue biomarkers, and levels of cardiovascular-related hormones. Recruitment began in June 2025 and is currently ongoing.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>This study provides an integrated physiological perspective on how 12-week moderate-intensity aerobic exercise influences cardiovascular function and systemic metabolism in patients with T2DM. We hypothesize that 12 weeks of aerobic exercise will significantly improve NMD and GWE, concurrent with enhanced metabolic flexibility and reduced fatigue compared to the non-exercise control group.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1748335","type":"journal-article","created":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T05:36:54Z","timestamp":1768973814000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Effects of aerobic exercise on integrated cardiovascular health and energy metabolism in patients with type 2 diabetes mellitus: study protocol for a randomized controlled trial"],"prefix":"10.3389","volume":"17","author":[{"given":"Shihe","family":"Wang","sequence":"first","affiliation":[{"name":"Liaoning Provincial Sports Development Center","place":["Shenyang, Liaoning, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhouyu","family":"Liu","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Dalian Medical University","place":["Dalian, Liaoning, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ning","family":"Feng","sequence":"additional","affiliation":[{"name":"College of Exercise and Health, Shenyang Sport University","place":["Shenyang, Liaoning, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaodong","family":"Guo","sequence":"additional","affiliation":[{"name":"Provincial University Key Laboratory of Sport and Health Science, School of Physical Education and Sport Sciences, Fujian Normal University","place":["Fuzhou, Fujian, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Chen","sequence":"additional","affiliation":[{"name":"Liaoning Provincial Sports Development Center","place":["Shenyang, Liaoning, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiyang","family":"Cao","sequence":"additional","affiliation":[{"name":"The QUEEN MARY School, Jiangxi Medical College, Nanchang University","place":["Nanchang, Jiangxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuelu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery and Oncology, The Second Hospital of Dalian Medical University","place":["Dalian, Liaoning, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Sun Yat\u2010sen Memorial Hospital of Sun Yat\u2010sen University","place":["Guangzhou, Guangdong, China"]},{"name":"Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical School","place":["Singapore, Singapore"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiwei","family":"Yan","sequence":"additional","affiliation":[{"name":"Liaoning Provincial Sports Development Center","place":["Shenyang, Liaoning, China"]},{"name":"Provincial University Key Laboratory of Sport and Health Science, School of Physical Education and Sport Sciences, Fujian Normal University","place":["Fuzhou, Fujian, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/s2213-8587(24)00127-x","article-title":"Managing insulin resistance: the forgotten pathophysiological component of type 2 diabetes","volume":"12","author":"Abdul-Ghani","year":"2024","journal-title":"Lancet Diabetes Endocrinol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1186\/s12933-018-0728-6","article-title":"Prevalence of cardiovascular disease in type 2 diabetes: A systematic literature review of scientific evidence from across the world in 2007-2017","volume":"17","author":"Einarson","year":"2018","journal-title":"Cardiovasc Diabetol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1007\/s11684-025-1141-7","article-title":"Premature mortality projection for diabetes to 2030: A subnational evaluation towards the healthy China 2030 goals","volume":"19","author":"Zhao","year":"2025","journal-title":"Front Med"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.14336\/ad.2023.1106","article-title":"Type-2 diabetes alters hippocampal neural oscillations and disrupts synchrony between the hippocampus and cortex","volume":"15","author":"Rabiller","year":"2024","journal-title":"Aging Dis"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2023.0524","article-title":"Oxidative stress, endothelial dysfunction, and N-acetylcysteine in type 2 diabetes mellitus","volume":"40","author":"Li","year":"2024","journal-title":"Antioxidants Redox Signaling"},{"key":"B6","doi-asserted-by":"publisher","first-page":"44","DOI":"10.2337\/db15-0627","article-title":"Relationship between left ventricular structural and metabolic remodeling in type 2 diabetes","volume":"65","author":"Levelt","year":"2016","journal-title":"Diabetes"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1161\/01.Cir.0000072789.89096.10","article-title":"Abnormal cardiac and skeletal muscle energy metabolism in patients with type 2 diabetes","volume":"107","author":"Scheuermann-Freestone","year":"2003","journal-title":"Circulation"},{"key":"B8","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/s13098-021-00781-x","article-title":"Assessment of subclinical left ventricle myocardial dysfunction using global myocardial work in type 2 diabetes mellitus patients with preserved left ventricle ejection fraction","volume":"14","author":"Wang","year":"2022","journal-title":"Diabetol Metab syndrome"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2840-11-127","article-title":"Determinants of vascular function in patients with type 2 diabetes","volume":"11","author":"Naka","year":"2012","journal-title":"Cardiovasc Diabetol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1161\/hypertensionaha.120.14778","article-title":"Adults with type 2 diabetes mellitus exhibit a greater exercise-induced increase in arterial stiffness and vessel hemodynamics","volume":"75","author":"Cooke","year":"2020","journal-title":"Hypertension (Dallas Tex: 1979)"},{"key":"B11","doi-asserted-by":"publisher","first-page":"e015771","DOI":"10.1161\/jaha.119.015771","article-title":"Age-specific associations between systolic blood pressure and cardiovascular disease: A 10-year diabetes mellitus cohort study","volume":"9","author":"Wan","year":"2020","journal-title":"J Am Heart Assoc"},{"key":"B12","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1016\/j.jacc.2022.05.031","article-title":"Cardiorespiratory Fitness and Mortality Risk across the Spectra of Age, Race, And sex","volume":"80","author":"Kokkinos","year":"2022","journal-title":"J Am Coll Cardiol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.31083\/j.rcm2507263","article-title":"Age, race, sex and cardiorespiratory fitness: implications for prevention and management of cardiometabolic disease in individuals with diabetes mellitus","volume":"25","author":"Nyl\u00e9n","year":"2024","journal-title":"Rev Cardiovasc Med"},{"key":"B14","doi-asserted-by":"publisher","first-page":"e0302831","DOI":"10.1371\/journal.pone.0302831","article-title":"Effectiveness of structured exercise program on insulin resistance and quality of life in type 2 diabetes mellitus-a randomized controlled trial","volume":"19","author":"Amaravadi","year":"2024","journal-title":"PLoS One"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.2009.165571","article-title":"Effects of exercise intervention on myocardial function in type 2 diabetes","volume":"95","author":"Hordern","year":"2009","journal-title":"Heart (British Cardiac Society)"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3934\/publichealth.2021018","article-title":"Level of physical activity and barriers to exercise in adults with type 2 diabetes","volume":"8","author":"Martin","year":"2021","journal-title":"AIMS Public Health"},{"key":"B17","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1186\/s12966-024-01615-5","article-title":"Device-measured sedentary time and intensity-specific physical activity in relation to all-cause and cardiovascular disease mortality: the uk biobank cohort study","volume":"21","author":"Rezende","year":"2024","journal-title":"Int J Behav Nutr Phys Act"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2012.03.003","article-title":"Fatigue symptoms relate to systemic inflammation in patients with type 2 diabetes","volume":"26","author":"Lasselin","year":"2012","journal-title":"Brain behavior Immun"},{"key":"B19","doi-asserted-by":"publisher","first-page":"S20","DOI":"10.2337\/dc24-S002","article-title":"Diagnosis and classification of diabetes: standards of care in diabetes-2024","volume":"47","year":"2024","journal-title":"Diabetes Care"},{"key":"B20","doi-asserted-by":"publisher","first-page":"e015716","DOI":"10.1161\/jaha.119.015716","article-title":"Effects of glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors, and their combination on endothelial glycocalyx, arterial function, and myocardial work index in patients with type 2 diabetes mellitus after 12-month treatment","volume":"9","author":"Ikonomidis","year":"2020","journal-title":"J Am Heart Assoc"},{"key":"B21","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1056\/NEJMoa012512","article-title":"Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin","volume":"346","author":"Knowler","year":"2002","journal-title":"New Engl J Med"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.apmr.2005.09.025","article-title":"Exercise training improves low-density lipoprotein oxidability in untrained subjects with coronary artery disease","volume":"87","author":"Ziegler","year":"2006","journal-title":"Arch Phys Med Rehabil"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1249\/mss.0000000000002800","article-title":"Exercise\/physical activity in individuals with type 2 diabetes: A consensus statement from the american college of sports medicine","volume":"54","author":"Kanaley","year":"2022","journal-title":"Med Sci sports Exercise"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.2337\/dc11-1655","article-title":"Metabolic effects of aerobic training and resistance training in type 2 diabetic subjects: A randomized controlled trial (the raed2 study)","volume":"35","author":"Bacchi","year":"2012","journal-title":"Diabetes Care"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.echo.2014.07.007","article-title":"Endurance training minimizes age-related changes of left ventricular twist-untwist mechanics","volume":"27","author":"Maufrais","year":"2014","journal-title":"J Am Soc Echocardiography"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2014.05.007","article-title":"A six-month exercise intervention in subclinical diabetic heart disease: effects on exercise capacity, autonomic and myocardial function","volume":"63","author":"Sacre","year":"2014","journal-title":"Metabolism: Clin Exp"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1161\/circimaging.109.934273","article-title":"Reduced end-systolic pressure-volume ratio response to exercise: A marker of subclinical myocardial disease\u00a0in type 2 diabetes","volume":"3","author":"Jellis","year":"2010","journal-title":"Circ Cardiovasc Imaging"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdiacomp.2024.108896","article-title":"Effects of moderate-intensity aerobic training on cardiac structure and function in type 2 mellitus diabetic rats: based on echocardiography and speckle tracking","volume":"38","author":"Huang","year":"2024","journal-title":"J Diabetes its complications"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1167","DOI":"10.3390\/antiox13101167","article-title":"Metabolomic profiling reveals that exercise lowers biomarkers of cardiac dysfunction in rats with type 2 diabetes","volume":"13","author":"Wang","year":"2024","journal-title":"Antioxidants (Basel Switzerland)"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2014-2028","article-title":"Glucose-related arterial stiffness and carotid artery remodeling: A study in normal subjects and type 2 diabetes patients","volume":"99","author":"Kozakova","year":"2014","journal-title":"J Clin Endocrinol Metab"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2012.07.035","article-title":"A randomized trial of exercise for blood pressure reduction in type 2 diabetes: effect on flow-mediated dilation and circulating biomarkers of endothelial function","volume":"224","author":"Barone Gibbs","year":"2012","journal-title":"Atherosclerosis"},{"key":"B32","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1186\/s12933-021-01314-6","article-title":"Mechanisms of reduced peak oxygen consumption in subjects with uncomplicated type 2 diabetes","volume":"20","author":"Nesti","year":"2021","journal-title":"Cardiovasc Diabetol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"881","DOI":"10.2165\/00007256-200636100-00006","article-title":"Central fatigue: the serotonin hypothesis and beyond","volume":"36","author":"Meeusen","year":"2006","journal-title":"Sports Med (Auckland NZ)"},{"key":"B34","doi-asserted-by":"publisher","first-page":"e2821","DOI":"10.1002\/dmrr.2821","article-title":"Muscle fatigability in type 2 diabetes","volume":"33","author":"Orlando","year":"2017","journal-title":"Diabetes\/metabolism Res Rev"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.31083\/j.rcm2512436","article-title":"Diabetes mellitus and cardiovascular disease: exploring epidemiology, pathophysiology, and treatment strategies","volume":"25","author":"Siam","year":"2024","journal-title":"Rev Cardiovasc Med"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.14336\/ad.2025.0233","article-title":"Type 2 diabetes mellitus: A metabolic model of accelerated aging - multi-organ mechanisms and intervention approaches","author":"Zhang","year":"2025","journal-title":"Aging Dis"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.14336\/ad.2023.1109-1","article-title":"Arterial aging and cerebrovascular function: impact of aerobic exercise training in older adults","volume":"15","author":"Tomoto","year":"2024","journal-title":"Aging Dis"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1748335\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T07:39:56Z","timestamp":1771918796000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1748335\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,21]]},"references-count":37,"alternative-id":["10.3389\/fendo.2026.1748335"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2026.1748335","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,21]]},"article-number":"1748335"}}