Effect of high-intensity interval training on muscle remodeling in rheumatoid arthritis compared to prediabetes

Abstract

BackgroundSarcopenic obesity, associated with greater risk of cardiovascular disease (CVD) and mortality in rheumatoid arthritis (RA), may be related to dysregulated muscle remodeling. To determine whether exercise training could improve remodeling, we measured changes in inter-relationships of plasma galectin-3, skeletal muscle cytokines, and muscle myostatin in patients with RA and prediabetes before and after a high-intensity interval training (HIIT) program.MethodsPreviously sedentary persons with either RA (n = 12) or prediabetes (n = 9) completed a 10-week supervised HIIT program. At baseline and after training, participants underwent body composition (Bod Pod®) and cardiopulmonary exercise testing, plasma collection, and vastus lateralis biopsies. Plasma galectin-3, muscle cytokines, muscle interleukin-1 beta (mIL-1β), mIL-6, mIL-8, muscle tumor necrosis factor-alpha (mTNF-α), mIL-10, and muscle myostatin were measured via enzyme-linked immunosorbent assays. An independent cohort of patients with RA (n = 47) and age-, gender-, and body mass index (BMI)-matched non-RA controls (n = 23) were used for additional analyses of galectin-3 inter-relationships.ResultsExercise training did not reduce mean concentration of galectin-3, muscle cytokines, or muscle myostatin in persons with either RA or prediabetes. However, training-induced alterations varied among individuals and were associated with cardiorespiratory fitness and body composition changes. Improved cardiorespiratory fitness (increased absolute peak maximal oxygen consumption, or VO2) correlated with reductions in galectin-3 (r = −0.57, P = 0.05 in RA; r = −0.48, P = 0.23 in prediabetes). Training-induced improvements in body composition were related to reductions in muscle IL-6 and TNF-α (r < −0.60 and P <0.05 for all). However, the association between increased lean mass and decreased muscle IL-6 association was stronger in prediabetes compared with RA (Fisher r-to-z P = 0.0004); in prediabetes but not RA, lean mass increases occurred in conjunction with reductions in muscle myostatin (r = −0.92; P <0.05; Fisher r-to-z P = 0.026). Subjects who received TNF inhibitors (n = 4) or hydroxychloroquine (n = 4) did not improve body composition with exercise training.ConclusionExercise responses in muscle myostatin, cytokines, and body composition were significantly greater in prediabetes than in RA, consistent with impaired muscle remodeling in RA. To maximize physiologic improvements with exercise training in RA, a better understanding is needed of skeletal muscle and physiologic responses to exercise training and their modulation by RA disease–specific features or pharmacologic agents or both.Trial registrationClinicalTrials.gov Identifier: NCT02528344. Registered on August 19, 2015.

Plasma MicroRNAs in Established Rheumatoid Arthritis Relate to Adiposity and Altered Plasma and Skeletal Muscle Cytokine and Metabolic Profiles

“…RA development, severity, and poor treatment responses are tied to obesity (13). Also, RA is associated with sarcopenia, altered skeletal muscle remodeling, and impaired oxidative metabolism (14, 15). While these metabolic impairments in RA are likely driven in part by epigenetic dysregulation (16), it is unclear whether RA-related miRNAs contribute to the RA comorbidities of obesity and altered metabolism.…”

Altered Skeletal Muscle Metabolic Pathways, Age, Systemic Inflammation, and Low Cardiorespiratory Fitness Associate with Improvements in Disease Activity Following High-Intensity Interval Training in Persons with Rheumatoid Arthritis

“…For HIIT RA cohort #2, persons with RA (n = 12) completed clinical assessments and underwent skeletal muscle biopsies before and after a 10-week treadmill walking HIIT program (5,17). Similar to the cross-sectional RA cohort #1, all RA participants satis ed the ACR 1987 RA classi cation criteria (19), had no medication changes for 3 months prior to or during the intervention, and were taking less than or equal to prednisone 5 mg per day.…”

“…In RA, chronic in ammation is strongly linked to impaired muscle function and "rheumatoid cachexia" or sarcopenic obesity (i.e., decreased muscle mass, increased fat mass, and intramuscular adiposity) (15). Further, the RA skeletal muscle molecular pro le is de ned by altered in ammatory cytokines and impairments in satellite cell function and oxidative metabolism (15)(16)(17)(18). Of particular interest to this study, it is unclear how these RA muscle molecular pathways speci cally 1) contribute to and are affected by in ammation and autoimmunity and 2) in uence and predict immune system changes with exercise training.…”

Physical Activity and Prevalence of Rheumatoid Arthritis in Korean Adults with Prediabetes in the 2009-2013 National Health Cohort Study

“…[21][22][23] Physical activity and glycemic control may be beneficial in the inhibition of RA progression as well as in the reduction of its prevalence in patients with prediabetes. 24) However, T. Yates study reported that intensive physical intervention or previous physical activity level did not significantly reduce 2-h post prandial or fasting blood glucose levels 25) in adults with prediabetes and the expression of inflammatory markers 14) in patients with either RA or prediabetes. Therefore, the association between the frequency of physical activity and prevalence of RA in adults with prediabetes is unclear.…”

“…IL-1 inhibitor and IL-10, a natural inhibitor of IL-1β, 11) resulting in decreased disease severity and inflammation in adults with RA, obesity, prediabetes and T2DM. [11][12] Physical activity significantly improved the joint motility, strength and functional ability in patients with either prediabetes or RA via altered pro-inflammatory muscle cytokines [13][14] and reduced the blood glucose levels, further lowering the risk for T2DM. 15) Unfortunately, 71% of adults with RA are unable to maintain normal physical activity, [16][17][18][19] owing to arthritis related barriers to physical activity.…”