Concurrent alteration in inflammatory biomarker gene expression and oxidative stress: how aerobic training and vitamin D improve T2DM

Abstract

Background Vitamin D (Vit D) supplementation and Aerobic Training (AT) exert several beneficial effects such as antioxidant and anti-inflammatory actions. The literature on the effects of AT and Vit D supplementation on the oxidative stress biomarkers and gene expression of inflammatory cytokines in patients with Type 2 Diabetes Mellitus (T2DM) is limited. The present study aimed to examine the effects of AT and Vit D supplementation on inflammation and oxidative stress signaling pathways in T2DM patients. Materials and methods In this single-blinded, randomized, placebo-controlled trial, 48 men with T2DM (aged 35–50 years with Body Mass Index (BMI) of 25–30 kg/m2) were randomly allocated into four groups: AT+Vit D (n = 10); AT + placebo (AT; n = 10); Vit D (n = 10), and Control + placebo (C; n = 10). The eight-week AT program was executed for 20–40 min/day, at 60–75% of heart rate maximum (HRmax), for 3 days/wks. The Vit D group received 50,000 IU of Vit D supplement capsules per week for 8 weeks. The serum levels of oxidative stress biomarkers and gene expression of inflammatory cytokines in the Peripheral Blood Mononuclear Cells (PBMCs) were evaluated using the RT-PCR method. To analyze the data, paired t-tests and one-way analysis of variance and Tukey’s post hoc test were used at the significance level of P < 0.05. Results The result shows that serum 25-OH-Vit D, total nitrite, Total Glutathione (GSH), Total Antioxidant Capacity (TAC), Superoxide Dismutase (SOD), Catalase (CAT), and Glutathione Peroxidase (GPX) increased; and insulin, Fasting Blood Glucose (FBG), Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), High Sensitivity C-Reactive Protein (hs-CRP), Malondialdehyde (MDA), glycated albumin, and Urinary 8-hydroxydeoxyguanine (8-OHdG) decreased significantly in all groups after 8 weeks, except for C. In addition, results of RT-PCR showed that AT+Vit D, Vit D, and AT significantly downregulated the gene expression of Tumor Necrosis Factor-Alpha (TNF-α), Interleukin-1 Beta (IL-1β), Mitogen-Activated Protein Kinases 1 (MAPK1), Nuclear Factor Kappa B (NF-κB) 1 (p50). It also upregulated Interleukin-4 (IL-4) gene expression, Peroxisome Proliferator-Activated Receptor Gamma (PPAR-γ) in T2DM patients compared to the C. Conclusion Additionally, the AT+Vit D group showed significantly lower insulin, FBG, HOMA-IR, hs-CRP, MDA, glycated albumin, urinary 8-OHdG, IL-1β, TNF-α, MAPK1, and NF-κB1 (p50) levels and significantly higher serum 25-OH-Vit D, total nitrite, GSH, TAC, CAT, SOD, GPX, IL-4, and PPAR-γ levels compared to the AT and Vit D groups. In T2DM patients, 8 weeks of AT+Vit D had a more significant impact on certain gene expressions related to inflammation and oxidative stress than Vit D or AT alone.

Role of vitamin d in patients with type 2 diabetes mellitus

“…En cuanto a la información sobre el rol de la vitamina D en pacientes con diabetes mellitus tipo 2 (Tabla 1), la mayoría de artículos se relacionaba con la diabetes mellitus tipo 2, pero también hacía más relación a los otros diferentes tipos de diabetes como la diabetes tipo 1 o sus complicaciones como neuropatía diabética, pie diabético o relacionadas al sistema cardiovascular. (11,13,14,16,17,19,23,24,25,26,27) Las características fundamentales del diseño y resultados de los estudios sobre el rol de la vitamina D en pacientes diabéticos tipo II se muestra en la Tabla 2.…”

“…HOMA IR -0,81 -0,06 HOMA-B: 0,01 5 Li et al (35) 2018 Hoseini et al (17) , observaron que la actividad física, es un indicador para reducir biomarcadores inflamatorios y proteínas, pero que pueden ser reforzadas para algún proceso inflamatorio a largo plazo. Además, concluyeron que al realizar ejercicios aeróbicos y mantener una suplementación de vitamina D, la relación cintura-cadera (WHR), el índice de masa corporal (IMC), el peso corporal (BW) y el porcentaje de grasa corporal (BFP), disminuyeron sus valores, pero si solo se hace administración del placebo, no hay ningún cambio.…”

“…Además, concluyeron que al realizar ejercicios aeróbicos y mantener una suplementación de vitamina D, la relación cintura-cadera (WHR), el índice de masa corporal (IMC), el peso corporal (BW) y el porcentaje de grasa corporal (BFP), disminuyeron sus valores, pero si solo se hace administración del placebo, no hay ningún cambio. (17) Mientras que la glucosa en ayunas, HOMA-IR, proteína C reactiva de alta sensibilidad (hs-CRP), albumina glicosilada, también ayuda a la disminución de sus valores; pero en cambio el glutatión hay un incremento. También se aprecia una disminución de interleucina 1 beta (destruye las células pancreáticas en DM2), factor de necrosis tumoral; mientras que interleucina 4 aumento, indicando que el ejercicio puede reforzar a largo plazo estos antiinflamatorios.…”

The Influence of Lifestyle and Treatment on Oxidative Stress and Inflammation in Diabetes

“…It has also been shown that intensified activity-interval + strength training is required to reduce insulin intake in patients with T1DM [ 45 ]. A study by Hoseini et al [ 46 ] examined the effects of aerobic training on markers of oxidative stress and inflammation in patients with t2 diabetes. They found that an eight week intervention in the form of AT activity positively influenced glycemic control, most likely through a mechanism of increased antioxidant defense and decreased inflammatory markers (IL-1β, hs-CRP, TNF-α, interferon-γ (IFN-γ)), and increased the production of anti-inflammatory cytokines (increase in IL-4).…”

“…They found that an eight week intervention in the form of AT activity positively influenced glycemic control, most likely through a mechanism of increased antioxidant defense and decreased inflammatory markers (IL-1β, hs-CRP, TNF-α, interferon-γ (IFN-γ)), and increased the production of anti-inflammatory cytokines (increase in IL-4). Due to the small number of participants, conclusions should be made cautiously; however, it seems that physical activity, particularly when combined with vitamin D supplementation, is able to reduce biomarkers of oxidative stress and inflammation in patients with T2DM [ 46 ].…”