BACKGROUND: Weight loss is a cornerstone of obesity treatment and diabetes mellitus type 2 (T2D) prevention, but its implementation in clinical practice is limited by its perceived burden and variability in response. Personalizing interventions to increase their success rate is an unmet clinical need. OBJECTIVE: Identification of predictive factors associated with successful weight loss after sequential exercise in women with obesity. METHODS: The study will consist of a 2-stage analytical approach, including a predictive validation study and a 2:1 randomized cross-over controlled trial. Women aged 25-45 years with obesity (BMI>30) will be included in the study. The intervention will consist of a progressive protocol of aerobic exercise on a treadmill and a bicycle ergometer. We will measure weight loss in terms of fat mass (FM) and fat-free mass (FFM), metabolic flexibility (MetFlex) as ΔRQ (change in respiratory quotient (VCO2/VO2) between basal and insulin-stimulated state during glucose clamp), insulin sensitivity, glucose tolerance, hemoglobin A1c, microbiome composition, and metabolomic signatures. RESULTS: Recruitment for the trial began in January 2024. A total of 12 participants were enrolled and randomized. Among them 6 participants have completed the first phase of the A-arm and 6 participants have completed the control period of the B-arm and their intervention is ongoing. Recruitment is ongoing. We expect the preliminary data from this study to be completed in 2026. CONCLUSIONS: This intervention will investigate whether whole body and gut MetFlex can be further explored and used as ex ante predictors of successful weight loss following exercise intervention, providing proof of concept and paving the way for personalized lifestyle interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT06329349; https://clinicaltrials.gov/study/NCT06329349. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/67570.

1st Faculty of Medicine Institute of Clinical and Experimental Medicine Prague Czech Republic

Clinical Research Department Kralovske Vinohrady University Hospital and 3rd Faculty of Medicine Charles University Prague Czech Republic

Department of Pathophysiology Centre for Research on Diabetes Metabolism and Nutrition 3rd Faculty of Medicine Charles University Prague Czech Republic

Faculty of Physical Education and Sport Charles University Prague Czech Republic

See more in PubMed

Sun Y, You W, Almeida F, Estabrooks P, Davy B. The effectiveness and cost of lifestyle interventions including nutrition education for diabetes prevention: a systematic review and meta-analysis. J Acad Nutr Diet. 2017;117(3):404–421.e36. doi: 10.1016/j.jand.2016.11.016. S2212-2672(16)31451-4 PubMed DOI PMC

American Diabetes Association Professional Practice Committee 8. Obesity and weight management for the prevention and treatment of type 2 diabetes: standards of care in diabetes-2024. Diabetes Care. 2024;47(Suppl 1):S145–S157. doi: 10.2337/dc24-S008.153942 PubMed DOI PMC

Thompson D, Karpe F, Lafontan M, Frayn K. Physical activity and exercise in the regulation of human adipose tissue physiology. Physiol Rev. 2012;92(1):157–191. doi: 10.1152/physrev.00012.2011. 92/1/157 PubMed DOI

Rossmeislová L, Malisová L, Kracmerová J, Tencerová M, Kovácová Z, Koc M, Siklová-Vítková M, Viquerie N, Langin D, Stich V. Weight loss improves the adipogenic capacity of human preadipocytes and modulates their secretory profile. Diabetes. 2013;62(6):1990–1995. doi: 10.2337/db12-0986. db12-0986 PubMed DOI PMC

King NA, Hopkins M, Caudwell P, Stubbs RJ, Blundell JE. Individual variability following 12 weeks of supervised exercise: identification and characterization of compensation for exercise-induced weight loss. Int J Obes (Lond) 2008;32(1):177–184. doi: 10.1038/sj.ijo.0803712.0803712 PubMed DOI

Sáez de Asteasu ML, Martínez-Velilla N, Zambom-Ferraresi F, Casas-Herrero Á, Cadore EL, Ramirez-Velez R, Izquierdo M. Inter-individual variability in response to exercise intervention or usual care in hospitalized older adults. J Cachexia Sarcopenia Muscle. 2019;10(6):1266–1275. doi: 10.1002/jcsm.12481. PubMed DOI PMC

Cifuentes L, Ghusn W, Feris F, Campos A, Sacoto D, De la Rosa A, McRae A, Rieck T, Mansfield S, Ewoldt J, Friend J, Grothe K, Lennon RJ, Hurtado MD, Clark MM, Camilleri M, Hensrud DD, Acosta A. Phenotype tailored lifestyle intervention on weight loss and cardiometabolic risk factors in adults with obesity: a single-centre, non-randomised, proof-of-concept study. EClinicalMedicine. 2023;58:101923. doi: 10.1016/j.eclinm.2023.101923. S2589-5370(23)00100-1 PubMed DOI PMC

Chen S, Dai Y, Ma X, Peng H, Wang D, Wang Y. Personalized optimal nutrition lifestyle for self obesity management using metaalgorithms. Sci Rep. 2022;12(1):12387. doi: 10.1038/s41598-022-16260-w. 10.1038/s41598-022-16260-w PubMed DOI PMC

Palmer BF, Clegg DJ. Metabolic flexibility and its impact on health outcomes. Mayo Clin Proc. 2022;97(4):761–776. doi: 10.1016/j.mayocp.2022.01.012. S0025-6196(22)00042-8 PubMed DOI

Bergouignan A, Antoun E, Momken I, Schoeller DA, Gauquelin-Koch G, Simon C, Blanc S. Effect of contrasted levels of habitual physical activity on metabolic flexibility. J Appl Physiol (1985) 2013;114(3):371–379. doi: 10.1152/japplphysiol.00458.2012. japplphysiol.00458.2012 PubMed DOI

Huffman KM, Redman LM, Landerman LR, Pieper CF, Stevens RD, Muehlbauer MJ, Wenner BR, Bain JR, Kraus VB, Newgard CB, Ravussin E, Kraus WE. Caloric restriction alters the metabolic response to a mixed-meal: results from a randomized, controlled trial. PLoS One. 2012;7(4):e28190. doi: 10.1371/journal.pone.0028190. PONE-D-11-13098 PubMed DOI PMC

Maruvada P, Leone V, Kaplan LM, Chang EB. The human microbiome and obesity: moving beyond associations. Cell Host Microbe. 2017;22(5):589–599. doi: 10.1016/j.chom.2017.10.005. S1931-3128(17)30440-7 PubMed DOI

Liu Y, Wang Y, Ni Y, Cheung CKY, Lam KSL, Wang Y, Xia Z, Ye D, Guo J, Tse MA, Panagiotou G, Xu A. Gut microbiome fermentation determines the efficacy of exercise for diabetes prevention. Cell Metab. 2020;31(1):77–91.e5. doi: 10.1016/j.cmet.2019.11.001. S1550-4131(19)30608-4 PubMed DOI

Hughes RL, Holscher HD. Fueling gut microbes: a review of the interaction between diet, exercise, and the gut microbiota in athletes. Adv Nutr. 2021;12(6):2190–2215. doi: 10.1093/advances/nmab077. S2161-8313(22)00500-2 PubMed DOI PMC

Riedl RA, Atkinson SN, Burnett CML, Grobe JL, Kirby JR. The gut microbiome, energy homeostasis, and implications for hypertension. Curr Hypertens Rep. 2017;19(4):27. doi: 10.1007/s11906-017-0721-6. 10.1007/s11906-017-0721-6 PubMed DOI PMC

From the American Association of Neurological Surgeons (AANS)‚ American Society of Neuroradiology (ASNR)‚ CardiovascularInterventional Radiology Society of Europe (CIRSE)‚ Canadian Interventional Radiology Association (CIRA)‚ Congress of Neurological Surgeons (CNS)‚ European Society of Minimally Invasive Neurological Therapy (ESMINT)‚ European Society of Neuroradiology (ESNR)‚ European Stroke Organization (ESO)‚ Society for Cardiovascular AngiographyInterventions (SCAI)‚ Society of Interventional Radiology (SIR)‚ Society of NeuroInterventional Surgery (SNIS)‚World Stroke Organization (WSO) Sacks D, Baxter B, Campbell BCV, Carpenter JS, Cognard C, Dippel D, Eesa M, Fischer U, Hausegger K, Hirsch JA, Shazam Hussain M, Jansen O, Jayaraman MV, Khalessi AA, Kluck BW, Lavine S, Meyers PM, Ramee S, Rüfenacht DA, Schirmer CM, Vorwerk D. Multisociety consensus quality improvement revised consensus statement for endovascular therapy of acute ischemic stroke. Int J Stroke. 2018;13(6):612–632. doi: 10.1177/1747493018778713. PubMed DOI

Oppert J, Bellicha A, van Baak MA, Battista F, Beaulieu K, Blundell JE, Carraça EV, Encantado J, Ermolao A, Pramono A, Farpour-Lambert N, Woodward E, Dicker D, Busetto L. Exercise training in the management of overweight and obesity in adults: synthesis of the evidence and recommendations from the European Association for the Study of Obesity Physical Activity Working Group. Obes Rev. 2021;22(Suppl 4):e13273. doi: 10.1111/obr.13273. PubMed DOI PMC

Donnelly JE, Honas JJ, Smith BK, Mayo MS, Gibson CA, Sullivan DK, Lee J, Herrmann SD, Lambourne K, Washburn RA. Aerobic exercise alone results in clinically significant weight loss for men and women: midwest exercise trial 2. Obesity (Silver Spring) 2013;21(3):E219–E228. doi: 10.1002/oby.20145. PubMed DOI PMC

Browning RC, Kram R. Energetic cost and preferred speed of walking in obese vs. normal weight women. Obes Res. 2005;13(5):891–899. doi: 10.1038/oby.2005.103. 13/5/891 PubMed DOI

Williamson DA, Bray GA, Ryan DH. Is 5% weight loss a satisfactory criterion to define clinically significant weight loss? Obesity (Silver Spring) 2015;23(12):2319–2320. doi: 10.1002/oby.21358. PubMed DOI

Reily NM, Pinkus RT, Vartanian LR, Faasse K. Compensatory eating after exercise in everyday life: insights from daily diary studies. PLoS One. 2023;18(3):e0282501. doi: 10.1371/journal.pone.0282501. PONE-D-22-32978 PubMed DOI PMC

Fedewa MV, Hathaway ED, Williams TD, Schmidt MD. Effect of exercise training on non-exercise physical activity: a systematic review and meta-analysis of randomized controlled trials. Sports Med. 2017;47(6):1171–1182. doi: 10.1007/s40279-016-0649-z.10.1007/s40279-016-0649-z PubMed DOI

Vetrovsky T, Omcirk D, Malecek J, Stastny P, Steffl M, Tufano JJ. Morning fatigue and structured exercise interact to affect non-exercise physical activity of fit and healthy older adults. BMC Geriatr. 2021;21(1):179. doi: 10.1186/s12877-021-02131-y. 10.1186/s12877-021-02131-y PubMed DOI PMC

Stechova K, Hlubik J, Pithova P, Cikl P, Lhotska L. Comprehensive analysis of the real lifestyles of T1D patients for the purpose of designing a personalized counselor for prandial insulin dosing. Nutrients. 2019;11(5):1148. doi: 10.3390/nu11051148. nu11051148 PubMed DOI PMC

Rowlands AV, Edwardson CL, Davies MJ, Khunti K, Harrington DM, Yates T. Beyond cut points: accelerometer metrics that capture the physical activity profile. Med Sci Sports Exerc. 2018;50(6):1323–1332. doi: 10.1249/MSS.0000000000001561. PubMed DOI

Chan AW, Tetzlaff JM, Altman DG, Laupacis A, Gøtzsche PC, Krleža-Jerić K, Hróbjartsson A, Mann H, Dickersin K, Berlin JA, Doré CJ, Parulekar WR, Summerskill WSM, Groves T, Schulz KF, Sox HC, Rockhold FW, Rennie D, Moher D. SPIRIT 2013 statement: defining standard protocol items for clinical trials. Ann Intern Med. 2013;158(3):200–207. doi: 10.7326/0003-4819-158-3-201302050-00583. 1556168 PubMed DOI PMC

Brown J, Alwan NA, West J, Brown S, McKinlay CJ, Farrar D, Crowther CA. Lifestyle interventions for the treatment of women with gestational diabetes. Cochrane Database Syst Rev. 2017;5(5):CD011970. doi: 10.1002/14651858.CD011970.pub2. PubMed DOI PMC

Zhang Y, Yang Y, Huang Q, Zhang Q, Li M, Wu Y. The effectiveness of lifestyle interventions for diabetes remission on patients with type 2 diabetes mellitus: a systematic review and meta-analysis. Worldviews Evid Based Nurs. 2023;20(1):64–78. doi: 10.1111/wvn.12608. PubMed DOI

Zucatti KP, Teixeira PP, Wayerbacher LF, Piccoli GF, Correia PE, Fonseca NKO, Moresco KS, Guerra BA, Maduré MG, Farenzena LP, Frankenberg AD, Brietzke E, Halpern B, Franco O, Colpani V, Gerchman F. Long-term effect of lifestyle interventions on the cardiovascular and all-cause mortality of subjects with prediabetes and type 2 diabetes: A systematic review and meta-analysis. Diabetes Care. 2022;45(11):2787–2795. doi: 10.2337/dc22-0642. 147815 PubMed DOI

Schellenberg ES, Dryden DM, Vandermeer B, Ha C, Korownyk C. Lifestyle interventions for patients with and at risk for type 2 diabetes: a systematic review and meta-analysis. Ann Intern Med. 2013;159(8):543–551. doi: 10.7326/0003-4819-159-8-201310150-00007. 1748845 PubMed DOI

da Rocha RB, Silva CS, Cardoso VS. Self-care in adults with type 2 diabetes mellitus: A systematic review. Curr Diabetes Rev. 2020;16(6):598–607. doi: 10.2174/1573399815666190702161849.CDR-EPUB-99351 PubMed DOI

See more in PubMed

ClinicalTrials.gov
NCT06329349