In a nationally representative US sample, higher physical activity levels were associated with lower insulin resistance, and systemic inflammation (measured by the systemic immune-inflammation index) accounted for a small proportion of this relationship.
Total physical activity was inversely associated with insulin resistance after multivariable adjustment.
The association between physical activity and insulin resistance was nonlinear, with a clear inverse relationship at low-to-moderate PA levels that became less certain at higher levels.
The systemic immune-inflammation index (SII) partially mediated the association between physical activity and insulin resistance.
Sensitivity analysis using multiple imputation for missing covariates showed a consistent inverse association between physical activity and insulin resistance.
The study used a cross-sectional design with data from six NHANES cycles spanning 2005 to 2016.
This research suggests that people who are more physically active tend to have lower insulin resistance, which is a condition where the body's cells don't respond well to insulin and is a key risk factor for type 2 diabetes and metabolic disease. Using data from over 9,000 U.S. adults collected between 2005 and 2016, the researchers found that the more physical activity people reported, the lower their insulin resistance tended to be. However, this benefit appeared most pronounced at low-to-moderate activity levels, with less clear benefit beyond roughly 1,922 metabolic equivalent minutes per week (a moderate-to-high level of weekly activity). The study also investigated whether systemic inflammation might explain part of why physical activity reduces insulin resistance. Using a measure called the systemic immune-inflammation index (SII), the researchers found that inflammation does partially mediate this relationship — meaning some of the benefit of physical activity on insulin resistance appears to work through reducing inflammation. However, this inflammatory pathway accounted for only a small portion of the total association, indicating that other mechanisms are also at play. This research suggests that encouraging physical activity — even at modest levels — may be a meaningful strategy for reducing insulin resistance and potentially lowering the risk of metabolic disorders like type 2 diabetes. The finding that benefits may plateau or become less certain at very high activity levels could be relevant for designing exercise recommendations, though the cross-sectional design of the study means causality cannot be definitively established.
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Upload Your LabsWang H, Jia Z. (2026). Association of physical activity with insulin resistance: A cross-sectional mediation analysis of the systemic immune-inflammation index in NHANES.. Medicine. https://doi.org/10.1097/MD.0000000000050465