Insulin-like Growth Factor 1 and Adiponectin and Associations with Muscle Deficits, Disease Characteristics, and Treatments in Rheumatoid Arthritis

Abstract

Objective: Rheumatoid arthritis (RA) is associated with low muscle mass and density. The objective of our study was to evaluate associations between 2 serum biomarkers [insulin-like growth factor 1 (IGF-1) and adiponectin] and skeletal muscle in RA.

Methods: Whole-body dual energy X-ray absorptiometry measures of the appendicular lean mass index (ALMI; kg/m(2)) and total fat mass index (kg/m(2)), as well as the peripheral quantitative computed tomography measures of the lower leg muscle and fat cross-sectional area (CSA; cm(2)) and muscle density (an index of fat infiltration) were obtained from 50 participants with RA, ages 18-70 years. Multivariable linear regression analyses evaluated associations between body composition and levels of adiponectin and IGF-1, adjusted for age, sex, and adiposity.

Results: Greater age was associated with higher adiponectin (p = 0.06) and lower IGF-1 (p = 0.004). Eight subjects had IGF-1 levels below the reference range for their age and sex. These subjects had significantly lower ALMI and muscle CSA in multivariable models. Lower IGF-1 levels were associated with greater clinical disease activity and severity, as well as low ALMI, muscle CSA, and muscle density (defined as 1 SD below normative mean). After adjusting for age and sex, greater adiponectin levels were associated with lower BMI (p = 0.02) as well as lower ALMI, and lower muscle CSA, independent of adiposity (p < 0.05). Only greater Health Assessment Questionnaire scores were significantly associated with lower adiponectin levels.

Conclusion: Low IGF-1 and greater adiponectin levels are associated with lower muscle mass in RA. Lower IGF-1 levels were seen in subjects with greater disease activity and severity.

Keywords: ADIPONECTIN; CACHEXIA; LEAN MASS; RHEUMATOID ARTHRITIS.

Figure 1

Serum IGF-1 and log-adjusted adiponectin levels among subjects with low muscle mass and low muscle density defined as age-, sex-, and race-specific Z score < −1 (15.9th percentile), adjusting for age, sex, and adiposity (FMI Z score for ALMI or fat CSA Z score for muscle CSA). IGF-1: insulin-like growth factor 1; FMI: fat mass index; ALMI: appendicular lean mass index; CSA: cross-sectional area.

Figure 2

Serum IGF-1 levels (mean and 95% CI) among subjects with increasing number of disease severity factors (CRP > 0.5 mg/dl, SvdH > 23, HAQ > 0, disease duration > 10 yrs, SJC > 1), adjusted for age and sex. IGF-1: insulin-like growth factor 1; CRP: C-reactive protein; SvdH: Sharp/van der Heijde method; HAQ: Health Assessment Questionnaire; SJC: swollen joint count.