Exercise-responsive endocrine-metabolic mediators in diabetes and cardiometabolic disorders: a systematic scoping...

Exercise-responsive endocrine-metabolic mediators may contribute to the systemic cardiometabolic adaptations induced by physical activity, but the literature spans diverse mediator classes, exercise paradigms, disease contexts, and experimental models. We conducted a systematic scoping review and evidence map to characterize the structure of this evidence and the biological relations examined across the field.

PubMed/MEDLINE, Web of Science Core Collection, and Scopus were searched from database inception through 7 August 2026. Titles and abstracts, followed by full texts, were independently assessed by two reviewers, with third-reviewer adjudication where required. Eligible primary reports underwent a separate round of independent full-text data charting using a relational framework linking reports, exercise contrasts, and mediator evidence. Cardiometabolic contexts and outcome domains were coded using multi-label rules, synonymous mediator terminology was harmonized, and companion publications were linked before study-level synthesis. Six potentially co-occurring evidence relations were mapped: exercise responsiveness, cardiometabolic association, source/secretion evidence, receptor/pathway evidence, functional perturbation, and formal mediation.

The searches yielded 3,388 records, of which 1,535 unique records underwent title/abstract screening and 397 reports underwent full-text assessment. The final primary evidence map comprised 365 reports representing 363 underlying studies, 413 exercise contrasts, 776 mediator-evidence observations, and 103 harmonized named mediators. Obesity/overweight was represented in 78.0% of studies. Among the 308 studies contributing named mediators, adipokines were represented in 58.4%, cytokines/chemokines in 32.1%, and myokines in 25.6%. Adiponectin, leptin, IL-6, and irisin were the most frequently represented named mediators. Exercise-responsive evidence and cardiometabolic associations were identified in 90.9% and 87.0% of contributing studies, respectively, whereas source/secretion evidence (18.5%), receptor/pathway evidence (9.7%), functional perturbation (11.4%), and formal mediation (0.3%) were less frequently represented. Chronic training accounted for 81.6% of exercise contrasts and aerobic/endurance exercise for 63.4%.

Exercise-responsive mediator research in cardiometabolic disease comprises a concentrated group of recurrent adipokines, cytokines, and myokines alongside a broad, sparsely studied mediator landscape. Exercise-responsive evidence and cardiometabolic associations were frequently represented, whereas direct investigation of tissue source, downstream pathways, functional perturbation, and formal mediation was less common. Studies integrating well-characterized exercise exposures with serial mediator assessment, source validation, and mechanistic testing may help define how exercise-responsive signaling contributes to cardiometabolic adaptation.