A low physical activity level is the main determinant of lower-than-normal TEE, and thus energy requirements, in women with RA.

Objective. To determine the effects of rheumatoid arthritis (RA) on whole-body protein metabolism.Methods. We examined protein metabolism and its hormonal and cytokine mediators before and 12 weeks after progressive resistance muscle strength training in 8 healthy young (mean k SD age 25 2 2 years) and 8 healthy elderly (70 rt 5 years) men and women, and in 8 adults with RA (42 2 13 years). An additional 6 healthy elderly subjects (69 k 3 years) served as a swimming-only control group.Results. Subjects with RA had higher rates of protein breakdown than did young or elderly healthy subjects (79.9 f 17.2 versus 60.3 f 5.8 and 63.7 2 12.4 pmoles/gm total body potassium/hour, respectively, P < 0.05), while there was no effect of age per se. Patients treated with methotrexate had normal rates of protein breakdown (P < 0.01 versus RA without methotrexate; P not significant versus healthy young subjects). Increased protein catabolism in RA was no longer evident after strength training. In multiple regression analysis, levels of tumor necrosis factor a (TNFa) (r = 0.47, P = 0.01) and growth hormone (r = -0.51, P = 0.006) were associated with protein breakdown, and plasma glucagon levels were inversely correlated with protein synthesis (r = -0.45, P =0.02). Growth hormone (r = -0.56, P = 0.002) and glucagon (r = 0.45, P = 0.04, levels were associated with protein oxidation.Conclusion. Adults with RA have increased whole-body protein breakdown, which correlates with growth hormone, glucagon, and TNFa production.Despite the many advances in our understanding of the disordered immune response that occurs in rheumatoid arthritis (RA), little information has been available about the effect of inflammation on metabolism and body composition in RA. Previous work from our laboratory has shown that body cell mass and physical activity are significantly reduced, and resting energy expenditure (REE) significantly increased, in patients with RA compared with healthy age-, sex-, race-, and weight-matched controls (1-3). This hypermetabolism of RA (defined as an increase in REE by >lo% above predicted levels) was directly associated with the production of tumor necrosis factor a (TNFa) and interleukin-lp (IL-1p) by peripheral blood mononuclear cells (PBMC) from these patients, which was approximately 2-fold higher than that in the control subjects. We have termed the cytokine-associated loss of lean body mass in RA rheumatoid cachexia, and have proposed that this cachexia is an important contributor to morbidity and mortality in RA, and offers insights into inflammatory mediators of cachexia (4).Understanding the mediators of the decline in body cell and protein mass is important because loss of more than -40% of baseline body cell mass is fatal, as shown in starvation, aging, and in acute illness (5). In

Objective. Patients with rheumatoid arthritis (RA) lose body cell mass (BCM) by unknown mechanisms. Since the loss of BCM in normal aging individuals parallels the characteristic age-related decline in growth hormone (GH) secretion, this study was carried out to determine whether further decreased GH secretion plays a role in the pathogenesis of this loss of BCM in RA patients, termed "rheumatoid cachexia."Methods. GH secretory kinetics were determined by deconvolution analysis in 16 patients with RA and 17 healthy controls matched for age (mean ؎ SD 45.4 ؎ 13.2 years and 47.1 ؎ 14.6 years, respectively), sex, race, and body mass index. Blood samples were obtained every 20 minutes for 24 hours. Body composition was ascertained using total-body potassium (TBK) as a measure of BCM and dual x-ray absorptiometry to determine fat mass.Results. BCM was reduced in patients with RA compared with healthy controls (mean ؎ SD gm TBK 79.5 ؎ 9.5 versus 94.9 ؎ 11.9; P < 0.0005), but there was no difference in fat mass. GH kinetic parameters in patients with RA did not differ from those in controls.Conclusion. These findings suggest that GH kinetics are unaltered in RA patients compared with healthy subjects; thus, GH deficiency does not account for rheumatoid cachexia.