Objectives
In prior reports, individuals with rheumatoid arthritis (RA) exhibited increased insulin resistance. However, these studies were limited by either suboptimal assessment methods for insulin sensitivity or a failure to account for important determinants, adiposity and physical activity. Our objectives were to carefully assess, compare and determine predictors of skeletal muscle insulin sensitivity (SI) in RA, accounting for adiposity and physical activity.
Methods
Thirty-nine individuals with established (seropositive or erosions) and treated RA and 39 age, gender, race, BMI, and physical activity-matched controls underwent a frequently-sampled intravenous glucose tolerance test to determine SI. Inflammation, body composition, and physical activity were assessed with systemic cytokine measurements, CT scans, and accelerometry, respectively. Exclusions were diabetes, cardiovascular disease, medication changes within three months, and prednisone use over 5 mg/d. This investigation was powered to detect a clinically significant, moderate effect size for SI difference.
Results
Despite elevated systemic inflammation (interleukin (IL)-6, IL-18, tumor necrosis factor-alpha; P<0.05 for all), persons with RA were not less insulin sensitive (SI geometric mean (SD): RA 4.0 (2.4) versus Control 4.9 (2.1)*10−5 min−1/[pmol/l]; P=0.39). Except for visceral adiposity being slightly greater in controls (P=0.03), there were no differences in body composition or physical activity. Lower SI was independently associated with increased abdominal and thigh adiposity, but not with cytokines, disease activity, duration, disability, or disease modifying medication use.
Conclusions
In established and treated RA, traditional risk factors, specifically excess adiposity, play more of a role in predicting skeletal muscle insulin sensitivity than systemic inflammation or other disease-related factors.