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/m2) and total fat mass index (kg/m2), as well as the peripheral quantitative computed tomography measures of the lower leg muscle and fat cross-sectional area (CSA; cm2) 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.

Anti-Hepatotoxic and Synergistic Effects of Sesame Oil With Methotrexate in Adjuvant Induced Arthritis

“…This reduction was significantly elevated in treated group with S.O or both doses of MTX. These results were in accordance with Baker et al, (2016) who found lower IGF-1 levels in RA patients with greater disease activity and severity. In the current study, MTX therapy caused deterioration in liver function as there was a significant elevation in liver enzymes and total billirubin serum levels accompanied with significant deplelion in the serum total protein.…”

Mechanisms of IGF-1-Mediated Regulation of Skeletal Muscle Hypertrophy and Atrophy

“…Local overexpression of IGF-1 has successfully rescued muscles in various chronic and experimental muscle atrophy models including Dex injected rats [ 115 ], age-related muscle atrophy [ 113 ], hindlimb suspension [ 156 ], and Ang II infusion in rodents [ 39 , 74 , 76 ], as well as in the mouse models of ALS [ 157 ] and muscular dystrophy [ 158 , 159 , 160 ]. Rheumatoid arthritis (RA) is associated with low muscle mass and density, and skeletal muscle of RA patients have been shown to have lower levels of IGF-1, which were associated with the severity of the disease, low appendicular lean mass, and lower myofiber CSA [ 161 ]. In a rat RA model, both circulating and skeletal muscle IGF-1 were decreased, the animals showed lower muscle mass, and subcutaneous injection of IGF-1 (100 µg/kg; twice daily for 12 days) increased body and hindlimb muscle weight without changing arthritis.…”

Muscle Deficits in Rheumatoid Arthritis Contribute to Inferior Cortical Bone Structure and Trabecular Bone Mineral Density

“…We previously demonstrated associations between adiponectin and evidence of cachexia in RA (40). The novel associations between adiponectin and bone outcomes observed in this RA cohort were independent of body composition.…”