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.