The relationship between weight status and metabolic syndrome in patients with rheumatoid arthritis and spondyloarthritis.

OBJECTIVES: To compare the prevalence and correlates of metabolic syndrome (MetS) stratified by body mass index (BMI) categories in rheumatoid arthritis (RA) and spondyloarthritis (SpA). METHODS: The age- and sex-standardized prevalence of MetS was calculated by BMI categories and compared between RA and SpA patients before starting first biologic, and controls. The determinants of metabolic syndrome in patients without obesity were investigated. RESULTS: MetS was observed in 28% of RA (21/75), 22.5% of SpA (18/80), 19% of controls (187/998). The age- and sex-standardized prevalence of MetS was not significantly different between RA 19% (95% CI: 11-27%), SpA 26% (95% CI: 16-36%) and controls 16% (95% CI: 14-18%). When stratified by BMI, the standardized prevalence of MetS was less frequent in obese RA patients (15%, 95% CI: 4-27%) compared to obese controls (48%, 95% CI: 40-55%) or to obese SpA (36%, 95% CI: 26-45%). In normal-weight RA patients, MetS standardized prevalence was 16% (95% CI: 7-25%) compared to 5% (95% CI: 0-11%) in SpA, and 6% (95% CI: 4-8%) in controls. In non-obese SpA, MetS was associated with abdominal obesity, visceral fat mass and cardiovascular risk. In non-obese RA patients with metabolic syndrome, body composition did not differ from metabolically healthy RA patients. CONCLUSIONS: MetS is not uniform among patients with similar BMI. In RA, MetS was less frequent in obese patients, and unlike SpA, was not associated with body fat composition in non-obese patients. Differences between RA and SpA for metabolic health suggest various pathophysiological mechanisms.

Alterations of HDL particle phospholipid composition and role of inflammation in rheumatoid arthritis.

The increased cardiovascular risk in RA (rheumatoid arthritis) cannot be explained by common quantitative circulating lipid parameters. The objective of the study was to characterize the modifications in HDL phosphosphingolipidome in patients with RA to identify qualitative modifications which could better predict the risk for CVD. Nineteen patients with RA were compared to control subjects paired for age, sex, BMI, and criteria of metabolic syndrome. The characterization of total HDL phosphosphingolipidome was performed by LC-MS/MS. RA was associated with an increased HDL content of lysophosphatidylcholine and a decreased content of PC (phosphatidylcholine), respectively, positively and negatively associated with cardiovascular risk. A discriminant molecular signature composed of 18 lipids was obtained in the HDL from RA patients. The detailed analysis of phospholipid species showed that molecules carrying omega-3 FA (fatty acids), notably docosahexaenoic acid (C22:6 n-3), were depleted in HDL isolated from RA patients. By contrast, two PE (phosphatidylethanolamine) species carrying arachidonic acid (C20:4 n-6) were increased in HDL from RA patients. Furthermore, disease activity and severity indexes were associated with altered HDL content of 4 PE and 2 PC species. In conclusion, the composition of HDL phosphosphingolipidome is altered during RA. Identification of a lipidomic signature could therefore represent a promising biomarker for CVD risk. Although a causal link remains to be demonstrated, pharmacological and nutritional interventions targeting the normalization of the FA composition of altered phospholipids could help to fight against RA-related inflammation and CVD risk.

Changes in body composition and metabolic profile during interleukin 6 inhibition in rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by increased mortality associated with cardiometabolic disorders including dyslipidaemia, insulin resistance, and cachectic obesity. Tumour necrosis factor inhibitors and interleukin 6 receptor blocker licensed for the treatment of RA decrease inflammation and could thus improve cardiovascular risk, but their effects on body composition and metabolic profile need to be clarified. We investigated the effects of tocilizumab (TCZ), a humanized anti-interleukin 6 receptor antibody, on body composition and metabolic profile in patients treated for RA. METHODS: Twenty-one active RA patients treated with TCZ were included in a 1 year open follow-up study. Waist circumference, body mass index, blood pressure, lipid profile, fasting glucose, insulin, serum levels of adipokines and pancreatic/gastrointestinal hormones, and body composition (dual-energy X-ray absorptiometry) were measured at baseline and 6 and 12 months of treatment. At baseline, RA patients were compared with 21 non-RA controls matched for age, sex, body mass index, and metabolic syndrome. RESULTS: Compared with controls, body composition was altered in RA with a decrease in total and appendicular lean mass, whereas fat composition was not modified. Among RA patients, 28.6% had a skeletal muscle mass index below the cut-off point for sarcopaenia (4.8% of controls). After 1 year of treatment with TCZ, there was a significant weight gain without changes for fat mass. In contrast, an increase in lean mass was observed with a significant gain in appendicular lean mass and skeletal muscle mass index between 6 and 12 months. Distribution of the fat was modified with a decrease in trunk/peripheral fat ratio and an increase in subcutaneous adipose tissue. No changes for waist circumference, blood pressure, fasting glucose, and atherogenic index were observed. CONCLUSIONS: Despite weight gain during treatment with TCZ, no increase in fat but a modification in fat distribution was observed. In contrast, muscle gain suggests that blocking IL-6 might be efficient in treating sarcopaenia associated with RA.