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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 diagnosed with RA and healthy controls will be recruited for an acute session of exercise. 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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| IL-6 blockade | Experimental | RA patients under pharmacological treatment with interleukin-6 blockade. |
|
| Anti-TNF-alpha | Experimental | RA patients under pharmacological treatment with anti-TNF-alpha. |
|
| Healthy controls | Experimental | Healthy participants. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Exercise | Behavioral | Thirty minutes of aerobic exercise in a treadmill. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Insulin sensitivity | Acute effect of exercise on insulin sensitivity assessed by the hyperinsulinemic euglycemic clamp. | 1 hour post-exercise |
| Measure | Description | Time Frame |
|---|---|---|
| Insulin sensitivity-related molecular pathway (Western Blotting) | Insulin sensitivity-related molecular pathway will be assessed by Western Blotting. | Baseline and 4 hours post-exercise |
| Insulin sensitivity-related molecular pathway (RT-PCR) |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Univsersity of Sao Paulo | Recruiting | São Paulo | 05508-030 | Brazil |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41106846 | Derived | Casale AR, Lemes IR, Smaira FI, Astley C, Oliveira-Junior G, de Sa Pinto AL, de Medeiros-Ribeiro AC, Godoy-Santos AL, Lima M, Carneiro CG, Buchpiguel CA, Dantas WS, Axelrod CL, Javvadi P, Ghosh S, Kirwan JP, Roschel H, Gualano B. Interleukin-6 blockade does not impair exercise-induced glucose uptake and insulin sensitivity in rheumatoid arthritis. Am J Physiol Endocrinol Metab. 2025 Dec 1;329(6):E849-E860. doi: 10.1152/ajpendo.00348.2025. Epub 2025 Oct 17. |
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| ID | Term |
|---|---|
| D001172 | Arthritis, Rheumatoid |
| ID | Term |
|---|---|
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
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| ID | Term |
|---|---|
| D015444 | Exercise |
| ID | Term |
|---|---|
| D009043 | Motor Activity |
| D009068 | Movement |
| D009142 | Musculoskeletal Physiological Phenomena |
| D055687 | Musculoskeletal and Neural Physiological Phenomena |
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RA patients will be divided into 2 groups, according to the pharmacological treatment (tocilizumab or anti-TNF). A third group will be composed by healthy controls. 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.
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Insulin sensitivity-related molecular pathway will be assessed by Real-Time Polymerase Chain Reaction (RT-PCR).
| Baseline and 4 hours post-exercise |
| Skeletal muscle glucose uptake | Positron emission tomography-magnetic resonance imaging (PET/MRI) will be performed to quantify skeletal muscle glucose uptake. | 3 hours post-exercise |
| D003240 |
| Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |