ArticleJournal of pain research2026
Type 2 Diabetes Mellitus Modifies the Association Between Exercise Therapy and Injury Risk and Long-Term Outcomes in Patients with Knee Osteoarthritis: A Retrospective Cohort Study.
Article in Journal of pain research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Introduction: Structured exercise is a core treatment for knee osteoarthritis (KOA), but whether its associations with musculoskeletal injury, knee arthroplasty utilization, and opioid use differ by type 2 diabetes mellitus (T2DM) status remains uncertain. Methods: This retrospective cohort study used electronic health records from 2014-2024. A 3-month landmark design classified patients as receiving structured exercise therapy or usual care. Propensity score matching yielded 1,329 pairs in the T2DM+KOA cohort and 3,441 pairs in the KOA-only cohort. Injury was analyzed using clustered Cox regression, total knee arthroplasty (TKA) utilization using Fine-Gray models, and opioid-use trajectories using group-based trajectory modeling. Results: Over 3.4 years of follow-up, exercise therapy was not significantly associated with injury in the KOA-only cohort (adjusted HR, 0.93; 95% CI, 0.76-1.13; p = 0.462), but was associated with increased injury risk in the T2DM+KOA cohort (adjusted HR, 1.39; 95% CI, 1.11-1.74; p = 0.004). The Exercise Therapy × T2DM interaction was significant (p = 0.006). Exercise therapy was associated with lower TKA utilization in the KOA-only cohort (adjusted subdistribution HR, 0.79; 95% CI, 0.68-0.92; p = 0.003), but not in the T2DM+KOA cohort (adjusted subdistribution HR, 0.92; 95% CI, 0.76-1.12; p = 0.408). The interaction was significant for the Progressive/Worsening opioid-use trajectory (OR, 1.71; 95% CI, 1.12-2.61; p = 0.014). Among patients with T2DM receiving exercise therapy, exploratory spline analysis showed a nonlinear association between glycated hemoglobin (HbA1c) and injury risk (p for nonlinearity = 0.006). Conclusion: Exercise therapy showed different associations with injury according to T2DM status, but causal treatment-effect modification cannot be inferred. It was associated with lower TKA utilization in the KOA-only cohort, whereas no significant association was observed in the T2DM+KOA cohort. The HbA1c finding was exploratory and requires external validation. Individualized assessment and monitoring warrant evaluation, particularly among patients with poorer glycemic control.
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