Muscle Pathology in Rheumatoid Arthritis: The Effects of Inflammation and Insulin Resistance

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Muscle Pathology in Rheumatoid Arthritis: The Effects of Inflammation and Insulin Resistance

Investigators found evidence that both aerobic and resistance training lowers insulin resistance, but further studies are needed to determine the specific effects in patients with rheumatoid arthritis.

Patients with rheumatoid arthritis (RA) typically experience reduced physical function early in the course of disease, with physical impairment accelerating over time to a greater degree than what is expected with normal aging.1 Even patients who have achieved low disease activity or remission through treat-to-target strategies have the physical function of healthy individuals 25 years older.2 Compared with the general population, individuals with RA are more sedentary and exercise less frequently.3 Although joint pain, swelling, and deformity have long been regarded as the primary contributors to functional disability in patients with RA,4,5 the downstream effect of inflammation on skeletal muscle has been implicated as another important cause.6

Unfavorable changes in body composition are common in patients with RA and believed to be mediated through metabolic perturbations.7 Rheumatoid cachexia, characterized by a decrease in lean muscle mass and an increase in total fat mass, is present in approximately 67% of individuals with stable RA, while obesity occurs in approximately 80%.2 Greater amounts of total and appendicular fat mass place patients with RA at higher risk for disability, while greater appendicular lean mass predicts lower rates of disability.5 Although there have been conflicting findings, some studies suggest that patients with RA are at an elevated risk for metabolic syndrome, a condition characterized by abdominal obesity, lipid abnormalities, hyperglycemia, and high blood pressure.8

In a recent review, Beatriz Hanaoka, MD, of the University of Alabama at Birmingham, and colleagues, discussed the mechanisms by which inflammation and insulin resistance exert deleterious effects on skeletal muscle homeostasis and function.9 Many of the proinflammatory cytokines implicated in the pathogenesis of RA, including interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, play a role in the loss of muscle mass by accelerating proteasome-dependent proteolysis and inhibiting anabolic and/or anticatabolic signaling.9 Excessive proinflammatory cytokines such as TNF-α can reduce the storage capacity of adipocytes in primary fat depots by suppressing the recruitment and differentiation of new adipocytes, resulting in the deposition of adipocytes in non-adipose tissues, including skeletal muscle.9,10 The infiltration of fat into muscle is associated with impaired physical function and low physical activity levels in patients with RA, an effect not seen in patients with fat accumulation outside the muscle.11 Insulin resistance is highly prevalent in patients with RA and has been associated with the loss of lean muscle mass.3 Factors associated with greater rates of insulin resistance in patients with RA include:

  • rheumatoid factor seropositivity
  • prednisone use
  • greater RA disease activity
  • visceral and thigh intermuscular adiposity
Read on: Muscle Pathology in Rheumatoid Arthritis: The Effects of Inflammation and Insulin Resistance

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