Background: Physical inactivity and Type 2 diabetes mellitus (T2DM)–associated inflammatory biomarkers are correlated with poor quality of life (QoL). However, no study has investigated the synergistic effect of physical activity (PA) and lower neutrophil–lymphocyte ratio (NLR) on QoL. Objective: We examined the independent and synergistic effects of PA and inflammatory biomarkers on three domains of QoL in T2DM. Methods: This cross-sectional study included 294 patients with T2DM from community clinics in Indonesia. The 36-item Short Form Survey and a questionnaire about PA engagement were used to measure QoL and metabolic equivalent of task (MET)-hr/week, respectively. Inflammatory biomarkers were measured in fasting blood. Adjusted coefficients β and 95% confidence interval (CI) were estimated using multiple linear regression. The synergistic effect was analyzed using additive interaction for linear regression. Results: Patients with PA ≥ 7.5 MET-hr/week exhibited significantly higher total QoL (β = 8.41, 95% CI = [6.04, 10.78]) and physical component score (PCS; β = 13.90, 95% CI = [10.52, 17.29]) than those with PA < 7.5 MET-hr/week. Patients with NLR < 1.940 had significantly higher total QoL (β = 4.76, 95% CI = [3.41, 6.11]), mental component score (MCS; β = 2.62, 95% CI = [0.75, 4.49]), and PCS (β = 6.89, 95% CI = [4.97, 8.82]) than patients with NLR ≥ 1.940. PA ≥ 7.5 MET-hr/week and NLR < 1.940 exhibited a synergistic effect on total QoL, MCS, and PCS. Conclusions: High PA level and low NLR had a positive synergistic effect on QoL among patients with T2DM.
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