Physical activity is associated with improved glycemic control but not with IL-6–glycemic interactions in type 2 diabetes: a cross-sectional study

Background Interleukin-6 (IL-6) exhibits both pro-inflammatory and exercise-induced myokine properties in type 2 diabetes mellitus (T2DM). Whether physical activity modifies the relationship between IL-6 and glycemic control remains unclear. Aim To examine the associations of physical activity and circulating IL-6 with glycemic and metabolic markers in individuals with T2DM, and to test for interaction effects. Methods A cross-sectional study with 185 T2DM participants (98 active, 87 sedentary) assessed circulating IL-6 levels alongside various glycemic and lipid markers. Multivariable regression with IL-6 × activity interaction terms was performed to test for effect modification. Results Circulating IL-6 levels did not differ significantly between active and sedentary participants. Physical activity was associated with significantly lower HbA1c, fasting glucose, HOMA-IR, and fructosamine levels. In unadjusted analyses, IL-6 showed inverse correlations with glycemic markers in active individuals but not in sedentary participants. However, in multivariable models, IL-6 was not independently associated with glycemic outcomes, and no significant IL-6 × activity interaction effects were observed. Conclusions Physical activity is associated with improved glycemic control in T2DM, whereas circulating IL-6 is not independently associated with metabolic outcomes and does not demonstrate activity-dependent interaction effects. Observed differences in unadjusted correlations should therefore be interpreted cautiously. These findings highlight the importance of accounting for confounding and interaction testing when evaluating cytokine–metabolic relationships. These findings are observational and hypothesis-generating and warrant confirmation in longitudinal studies.

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