Exercise Volume Modulates Cardiac Protection in a Type 2 Diabetic Rat Model: Differential Effects of High- and Low-Volume Moderate-Intensity Endurance Exercise Training on Diabetic Cardiomyopathy

Exercise Volume Modulates Cardiac Protection in a Type 2 Diabetic Rat Model: Differential Effects of High- and Low-Volume Moderate-Intensity Endurance Exercise Training on Diabetic Cardiomyopathy | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Exercise Volume Modulates Cardiac Protection in a Type 2 Diabetic Rat Model: Differential Effects of High- and Low-Volume Moderate-Intensity Endurance Exercise Training on Diabetic Cardiomyopathy Rob Simons, Ileana Bonilauri, Lotte Vastmans, Lisa Steegen, Ellen Heeren, and 10 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8434440/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 01 May, 2026 Read the published version in Cardiovascular Diabetology – Endocrinology Reports → Version 1 posted 10 You are reading this latest preprint version Abstract Background Cardiomyopathy is a major complication of type 2 diabetes, whose prevalence continues to rise globally. Although major cardiology and endocrinology societies endorse exercise training to reduce cardiovascular risk, the optimal exercise training modality, and specifically the role of exercise volume, in preventing diabetic cardiomyopathy remains unclear. Methods Male Sprague Dawley rats were fed a high-sugar diet to induce type 2 diabetes. At diet onset, animals were assigned to high-volume (HVE, N = 7) or low-volume (LVE, N = 8) moderate-intensity treadmill training, performed five days per week for 18 weeks. Sedentary rats served as controls (N = 6). Cardiac function was assessed using conventional echocardiography, strain imaging, and invasive hemodynamics. Plasma analyses were used to identify systemic metabolic status, and ex vivo techniques quantified left ventricular cardiac fibrosis, oxidative stress, hypertrophy, inflammation, and metabolism. Results After 18 weeks of diet, sedentary rats developed characteristic features of early-stage diabetic cardiomyopathy, accompanied by impaired systolic function and increased interstitial myocardial fibrosis. Conversely, high volumes of moderate-intensity exercise training partially prevented pathological cardiac remodelling by improving cardiac metabolic regulation, reducing oxidative stress, and enhancing both cardiac stress-responses and systemic metabolic control. Lower volumes of exercise training primarily reduced oxidative stress and inflammation, resulting in only modest cardioprotective effects and limited preservation of cardiac function. By contrast, high-volume exercise training elicited more pronounced cardioprotective effects, reflected by a significantly higher ejection fraction (p < 0.006), cardiac output (p < 0.002), and stroke volume index (p < 0.006) relative to sedentary controls. Conclusion The progression of diabetic cardiomyopathy is strongly modulated by the volume of exercise. High-volume moderate-intensity exercise training confers superior cardioprotection compared with low-volume training, underscoring the importance of incorporating sufficient exercise volume into evidence-based exercise prescriptions for individuals with type 2 diabetes. diabetes cardiomyopathy aerobic training exercise volume preclinical study Full Text Additional Declarations No competing interests reported. Supplementary Files SupplementalfiguresFinal.docx Cite Share Download PDF Status: Published Journal Publication published 01 May, 2026 Read the published version in Cardiovascular Diabetology – Endocrinology Reports → Version 1 posted Editorial decision: Revision requested 03 Mar, 2026 Reviews received at journal 03 Mar, 2026 Reviewers agreed at journal 01 Mar, 2026 Reviews received at journal 28 Feb, 2026 Reviewers agreed at journal 24 Feb, 2026 Reviewers agreed at journal 24 Feb, 2026 Reviewers invited by journal 24 Feb, 2026 Editor assigned by journal 10 Jan, 2026 Submission checks completed at journal 10 Jan, 2026 First submitted to journal 09 Jan, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8434440","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":596608516,"identity":"aae0afa8-8f9c-4848-ac91-7764eb7cd018","order_by":0,"name":"Rob Simons","email":"","orcid":"","institution":"Hasselt University","correspondingAuthor":false,"prefix":"","firstName":"Rob","middleName":"","lastName":"Simons","suffix":""},{"id":596608519,"identity":"4aef04b2-21c6-4fc0-823c-7840758810dc","order_by":1,"name":"Ileana Bonilauri","email":"","orcid":"","institution":"University of 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Cardiomyopathy","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":false,"email":"","identity":"cardiovascular-diabetology-endocrinology-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"","title":"Cardiovascular Diabetology – Endocrinology Reports","twitterHandle":"","acdcEnabled":false,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"Unsupported Journal","inReviewEnabled":false,"inReviewRevisionsEnabled":false},"keywords":"diabetes, cardiomyopathy, aerobic training, exercise volume, preclinical study","lastPublishedDoi":"10.21203/rs.3.rs-8434440/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8434440/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eCardiomyopathy is a major complication of type 2 diabetes, whose prevalence continues to rise globally. Although major cardiology and endocrinology societies endorse exercise training to reduce cardiovascular risk, the optimal exercise training modality, and specifically the role of exercise volume, in preventing diabetic cardiomyopathy remains unclear.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eMale Sprague Dawley rats were fed a high-sugar diet to induce type 2 diabetes. At diet onset, animals were assigned to high-volume (HVE, N\u0026thinsp;=\u0026thinsp;7) or low-volume (LVE, N\u0026thinsp;=\u0026thinsp;8) moderate-intensity treadmill training, performed five days per week for 18 weeks. Sedentary rats served as controls (N\u0026thinsp;=\u0026thinsp;6). Cardiac function was assessed using conventional echocardiography, strain imaging, and invasive hemodynamics. Plasma analyses were used to identify systemic metabolic status, and \u003cem\u003eex vivo\u003c/em\u003e techniques quantified left ventricular cardiac fibrosis, oxidative stress, hypertrophy, inflammation, and metabolism.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAfter 18 weeks of diet, sedentary rats developed characteristic features of early-stage diabetic cardiomyopathy, accompanied by impaired systolic function and increased interstitial myocardial fibrosis. Conversely, high volumes of moderate-intensity exercise training partially prevented pathological cardiac remodelling by improving cardiac metabolic regulation, reducing oxidative stress, and enhancing both cardiac stress-responses and systemic metabolic control. Lower volumes of exercise training primarily reduced oxidative stress and inflammation, resulting in only modest cardioprotective effects and limited preservation of cardiac function. By contrast, high-volume exercise training elicited more pronounced cardioprotective effects, reflected by a significantly higher ejection fraction (p\u0026thinsp;\u0026lt;\u0026thinsp;0.006), cardiac output (p\u0026thinsp;\u0026lt;\u0026thinsp;0.002), and stroke volume index (p\u0026thinsp;\u0026lt;\u0026thinsp;0.006) relative to sedentary controls.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThe progression of diabetic cardiomyopathy is strongly modulated by the volume of exercise. High-volume moderate-intensity exercise training confers superior cardioprotection compared with low-volume training, underscoring the importance of incorporating sufficient exercise volume into evidence-based exercise prescriptions for individuals with type 2 diabetes.\u003c/p\u003e","manuscriptTitle":"Exercise Volume Modulates Cardiac Protection in a Type 2 Diabetic Rat Model: Differential Effects of High- and Low-Volume Moderate-Intensity Endurance Exercise Training on Diabetic Cardiomyopathy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-26 19:09:36","doi":"10.21203/rs.3.rs-8434440/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-03-03T19:56:42+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-03T17:01:43+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"159262830308011427785686101584007840805","date":"2026-03-01T19:38:16+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-28T09:52:51+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"90819620877038716459963988408218624977","date":"2026-02-25T02:09:29+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"289624661567367141384146186516955122139","date":"2026-02-24T17:01:22+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-24T15:39:09+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-10T17:38:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-10T11:39:55+00:00","index":"","fulltext":""},{"type":"submitted","content":"Cardiovascular Diabetology – Endocrinology Reports","date":"2026-01-09T11:54:21+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":false,"email":"","identity":"cardiovascular-diabetology-endocrinology-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"","title":"Cardiovascular Diabetology – Endocrinology Reports","twitterHandle":"","acdcEnabled":false,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"Unsupported Journal","inReviewEnabled":false,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"954a1005-529a-432a-8491-13e89a8b4d61","owner":[],"postedDate":"February 26th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-05-04T16:03:13+00:00","versionOfRecord":{"articleIdentity":"rs-8434440","link":"https://doi.org/10.1186/s40842-026-00288-2","journal":{"identity":"cardiovascular-diabetology-endocrinology-reports","isVorOnly":false,"title":"Cardiovascular Diabetology – Endocrinology Reports"},"publishedOn":"2026-05-01 15:57:35","publishedOnDateReadable":"May 1st, 2026"},"versionCreatedAt":"2026-02-26 19:09:36","video":"","vorDoi":"10.1186/s40842-026-00288-2","vorDoiUrl":"https://doi.org/10.1186/s40842-026-00288-2","workflowStages":[]},"version":"v1","identity":"rs-8434440","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8434440","identity":"rs-8434440","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}