Adding Different Exercise Training Volumes to a Diet-Induced Weight Loss Facilitates Fat Loss and Maintains Fat-Free Mass in a Dose-Depending Fashion in Persons with Newly Diagnosed Type 2 Diabetes: Secondary Findings from the DOSE-EX Multi-Arm, Parallel-Group, Randomized Trial

OBJECTIVE - To assess the dose-response effects of exercise in combination with a diet-induced weight loss on fat mass (FM) percentage (FM%) in persons with diagnosed type 2 diabetes. RESEARCH DESIGN AND METHODS - In this secondary analysis of a four-armed randomized trial (Clinicaltrials.gov [NCT03769883][1]) 82 persons (35% females, mean age and standard deviation (SD) 58.2 (9.8) years) living with type 2 diabetes were randomly allocated to the control group (N=21, CON), diet control (25% energy restriction; N=20, DCON), diet control and exercise three times/week (two sessions of aerobic and one session combining resistance and aerobic training; N=20, MED), or diet control and exercise six times/week (four sessions of aerobic and two sessions combining resistance and aerobic training; N=21, HED) for 16 weeks. The primary outcome was the change in FM percentage points (pp). Secondary outcomes included fat-free mass and visceral adipose tissue volume. RESULTS- Type 2 diabetes duration was 4.0 years (interquartile range 1.9 to 5.5), body weight (SD) 101.4 kg (14.6), FM% (SD) 39.4 (6.7). FMpp decreased compared to standard care -3.5 pp (95% CI -5.6 to -1.4) p=0.002, -6.3 pp (CI -8.4 to -4.1) p<0.001, and -8.0 pp (95% CI -10.2 to -5.8) p<0.001, for DCON, MED, and HED, respectively. The difference between HED and MED was -1.8 pp [95% CI -3.9 to 0.4]; p=0.11). CONCLUSIONS- All interventions were superior in reducing FMpp compared to standard care in a dose-dependent manner. Adding three or six sessions of exercise to a low-calorie diet was superior in reducing FM compared to a low-calorie diet alone. ### Competing Interest Statement TPA owns stocks in NovoNordisk A/S. TPJS owns an academic consulting business (Blazon Scientific) and an endurance and nutrition consulting business (Veohtu). these companies had no control over the research design, data analysis, or publication outcomes of this work. ### Clinical Trial NCT03769883 ### Funding Statement The project was supported by a grant from TrygFonden and Svend Andersen Fonden. The Centre for Physical Activity Research is supported by TrygFonden (grants ID 101390, ID 20045, and ID 125132). Mark Preben Printz Lyngbaek was supported by a research grant from the Danish Diabetes Academy, which is funded by the Novo Nordisk Foundation, grant number NNF17SA0031406. Cody Durrer was supported by the Canadian Institutes of Health Research (MFE-176582). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study, which this study is a secondary analysis of, was approved by the Scientific Ethical Committee of the Capital Region of Denmark (approval number H-18038298). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data are not available for download due to privacy/ethical restrictions under the EU GDPR. Specific requests for access to the trial and unique biological data as well as code may be sent to the corresponding author. Based on the request access may be provided to a named individual in agreement with the rules and regulations of the Danish Data Protection Agency and the National Committee on Health Research Ethics. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT03769883&atom=%2Fmedrxiv%2Fearly%2F2023%2F06%2F06%2F2023.06.04.23290749.atom