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Impact of interleukin-6 receptor blockade on acute response to exercise on insulin sensitivity and muscle glucose uptake in patients with Rheumatoid Arthritis

Grant number: 20/04877-8
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): August 01, 2021
Effective date (End): July 31, 2023
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal researcher:Bruno Gualano
Grantee:Ítalo Ribeiro Lemes
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Rheumatoid Arthritis (RA) is a chronic inflammatory disease that affects the joints, causing pain, edema, physical disability and poor quality of life. In addition, RA patients are at increased risk of developing cardiovascular disease (CVD) and premature death. The most effective pharmacological treatment is the use of biological agents that inhibit the action of specific substances, such as interleukin 6 (IL-6) and Tumor Necrosis Factors (TNF). Physical exercise is considered a first-line non-pharmacological treatment in RA, improving inflammatory and metabolic profile, functional capacity, fatigue and preventing the onset of CVD. There is evidence that IL-6, when secreted as a result of exercise, brings several benefits. However, there is no study investigating the interaction between biological IL-6 blocking agents and exercise on metabolic responses, such as insulin sensitivity and glucose uptake, in patients with RA. To answer this question, adult women (s 18 years old) diagnosed with RA (n = 30) and healthy (n = 15) controls will be recruited for an acute session of combined exercise (aerobic and resistance). RA patients will be divided into 2 groups, according to the pharmacological treatment (tocilizumab or anti-TNF). The acute responses of insulin sensitivity after an acute session of exercise will be assessed by the hyperinsulinemic euglycemic clamp, and the molecular pathways will be assessed by muscle biopsy and gene and protein expression analysis. Positron Emission Tomography-Magnetic Resonance Imaging (PET/MRI) will be performed to quantify skeletal muscle glucose uptake. Between group comparisons will be performed by repeated measures analysis, with group and time as fixed factors and participants as random factor. If necessary, Tukey post hoc test will be performed. Statistical significance will be set at 5%. (AU)

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