BACKGROUND: Type 2 Diabetes Mellitus (T2DM) is one of the health issues causing untoward low-grade systemic inflammation. Aerobic Training (AT) and Vitamin D (Vit D) supplementation are among the approaches that improve lipid profile and liver enzymes in T2DM. However, the mechanisms responsible for these improvements are not fully elucidated. OBJECTIVES: This study aimed to evaluate the effects of AT and Vit D supplementation on lipid profile, liver enzymes, Interleukin-6 (IL-6), Interleukin-10 (IL-10), Cluster of differentiation 27 (CD27), Chemokine (C-X-C motif) Ligand 13 (CXCL13), Interferon-Gamma (IFN-gamma) and Transforming Growth Factor-Beta 1 (TGF-beta1) gene expressions in patients with T2DM. METHODS: In this study, 40 male T2DM patients aged 35 to 50 years were randomly selected and assigned into four groups (n = 10 for each); AT + vitamin D supplementation (AT + Vit D), AT + placebo (AT), Vit D supplementation (Vit D), and control + placebo (C). The intervention consisted of 8 weeks of 20 to 40 minutes AT protocol at 60 to 75% HRmax 3 sessions/week and taking 50,000 IU of Vit D supplement once a week. Serum levels of lipid profile and liver enzymes and gene expression of IL-6, IL-10, CD27, CXCL13, IFN-gamma, and TGF-beta1 in Peripheral Blood Mononuclear Cells (PBMCs) were measured. One-way analysis of variance (ANOVA), Tukey's post hoc, and paired sample t-test at P-values less than 0.05 were used to analyze the data using SPSS software. RESULTS: AT + Vit D, AT, and Vit D significantly decreased TC, TG, LDL, AST, ALT, and GGT while increased HDL after 8 weeks in favor of AT + Vit D. Also, gene expressions of IL-6, IL-10, CD27, CXCL13, IFN-gamma, and TGF-beta1 were downregulated significantly in AT + Vit D, AT, and Vit D, while upregulated in C. Furthermore, compared to individual AT or Vit D, AT + Vit D significantly downregulated IL-6 (p = 0.013; p = 0.025), IL-10 (p = 0.012; p = 0.026), CD27 (p = 0.023; p = 0.041), CXCL13 (p = 0.014; p = 0.025), IFN-gamma (p = 0.017; p = 0.026), and TGF-beta1 (p = 0.001; p = 0.028). CONCLUSION: In comparison to individual AT or Vit D, AT + Vit D may enhance lipid profile, and liver enzymes and drive the balance to favor inhibition of inflammation by downregulating gene expression of inflammation-related factors. As a result, AT + Vit D may be considered appropriate therapy for managing T2DM.

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