Effect of interleukin 6 blockers on body composition, adipocytokines and insulin-like growth factor 1 in patients with rheumatoid arthritis

Rheumatoid arthritis (RA) is characterised by functional disability and inflammation. This review explores the beneficial effects of exercise on function and cardiovascular disease risk in RA and explores the possibility that some of these beneficial effects may be moderated via exercise-induced improvements in body composition.

Editor's evaluation: The effects of caloric restriction on adipose tissue and metabolic health are sex- and age-dependent

Both baseline cardiorespiratory fitness and adiposity predict the risk of cancer mortality. However, the effects of changes in these two factors over time have not been evaluated thoroughly. The aim of this study was to examine the independent and joint associations of changes in cardiorespiratory fitness and body composition on cancer mortality. The cohort consisted of 13,930 men (initially cancer-free) with two or more medical examinations from 1974 to 2002. Cardiorespiratory fitness was assessed by a maximal treadmill exercise test, and body composition was expressed by body mass index (BMI) and percent body fat. Changes in cardiorespiratory fitness and body composition between the baseline and the last examination were classified into loss, stable, and gain groups. There were 386 deaths from cancer during an average of 12.5 yr of follow-up. After adjusting for possible confounders and BMI, change hazard ratios (95% confidence intervals) of cancer mortality were 0.74 (0.57-0.96) for stable fitness and 0.74 (0.56-0.98) for fitness gain. Inverse dose-response relationships were observed between changes in maximal METs and cancer mortality (P for linear trend = 0.05). Neither BMI change nor percent body fat change was associated with cancer mortality after adjusting for possible confounders and maximal METs change. In the joint analyses, men who became less fit had a higher risk of cancer mortality (P for linear trend = 0.03) compared with those who became more fit, regardless of BMI change levels. Being unfit or losing cardiorespiratory fitness over time was found to predict cancer mortality in men. Improving or maintaining adequate levels of cardiorespiratory fitness appears to be important for decreasing cancer mortality in men.

Several investigations that yielded different results in terms of net changes in body composition of weight-losing cancer patients have been reported that employed a variety of methods based on fundamentally different technology. Most of those reports were cross-sectional, whereas to the authors' knowledge there is sparse information available on longitudinal follow-up measurements in relation to other independent methods for the assessment of metabolism and performance. For the current report, the authors evaluated time course changes in body composition (dual-energy X-ray absorptiometry) with measurements of whole body and regional distribution of fat and lean tissue in relation to food and dietary intake, host metabolism (indirect calorimetry), maximum exercise capacity (walking test), and circulating hormones in cancer patients who were receiving palliative care during 4-62 months of follow-up. The entire cohort comprised 311 patients, ages 68 years +/- 3 years who were diagnosed with solid gastrointestinal tumors (84 colorectal tumors, 74 pancreatic tumors, 73 upper gastrointestinal tumors, 51 liver-biliary tumors, 3 breast tumors, 5 melanomas, and 21 other tumor types). Decreased body weight was explained by loss of body fat, preferentially from the trunk, followed by leg tissue and arm tissue, respectively. Lean tissue (fat-free mass) was lost from arm tissue, whereas trunk and leg tissue compartments increased, all concomitant with declines in serum albumin, increased systemic inflammation (C-reactive protein, erythrocyte sedimentation rate), increased serum insulin, and elevated daily caloric intake; whereas serum insulin-like growth factor 1 (IGF-1), resting energy expenditure, and maximum exercise capacity remained unchanged in the same patients. Serum albumin levels (P < 0.001), whole body fat (P < 0.02), and caloric intake (P < 0.001) predicted survival, whereas lean tissue mass did not. Daily intake of fat and carbohydrate was more important for predicting survival than protein intake. Survival also was predicted by serum IGF-1, insulin, leptin, and ghrelin levels (P < 0.02 - P < 0.001). Serum insulin, leptin, and ghrelin (total) levels predicted body fat (P < 0.001), whereas IGF-1 and thyroid hormone levels (T3, free T3) predicted lean tissue mass (P < 0.01). Systemic inflammation primarily explained variation in lean tissue and secondarily explained loss in body fat. Depletion of lean arm tissue was related most to short survival compared with the depletion of lean leg and trunk tissue. The current results demonstrated that body fat was lost more rapidly than lean tissue in progressive cancer cachexia, a phenomenon that was related highly to alterations in the levels of circulating classic hormones and food intake, including both caloric amount and diet composition. The results showed importance in the planning of efficient palliative treatment for cancer patients.

IntroductionRheumatoid arthritis (RA) is associated with changes in body composition and bone mineral density (BMD). The purpose of the present study was to evaluate whether anti-TNF treatment in early RA has an impact on body composition and BMD besides that which could be achieved by intensive disease-modifying anti-rheumatic drug (DMARD) combination therapy.MethodsForty patients with early RA who failed treatment with methotrexate up to 20 mg/week for 3 months were randomised to addition of sulphasalazine and hydroxychloroquine (treatment A) or addition of infliximab (treatment B). At 3, 12 and 24 months, body composition and BMD were assessed by total-body dual-energy X-ray absorptiometry. At the same time points, leptin, adiponectin, apolipoproteins, insulin-like growth factor-1 (IGF-1) and markers of bone remodelling were analysed. Compliance to treatment was considered in the analyses. Data were analysed with a mixed, linear model.ResultsPatients treated with anti-TNF had a significant increase in fat mass at 2 years, 3.8 (1.6 to 5.9) kg, in contrast to patients in treatment A, 0.4 (-1.5 to 2.2) kg (P = 0.040), despite similar reduction in disease activity. Both treatment strategies prevented loss of muscle mass and bone. Leptin concentrations increased significantly in both groups at 2 years and adiponectin increased significantly at 2 years in treatment A and at 1 year in treatment B. There were no significant changes in apolipoproteins or IGF-1. The markers of bone resorption decreased at 12 months in both treatment groups with no significant difference between the treatment groups.ConclusionsInfliximab therapy increased body fat mass, an effect that was not achieved with the combination of DMARDs, despite a similar reduction in disease activity, and thus seemed to be drug specific. The increase of fat mass was not associated with an exacerbated atherogenic lipid profile. Leptin and adiponectin concentrations increased in both treatment groups. The increase of adiponectin may partially explain the reduced frequency of cardiovascular diseases found when disease activity is reduced in RA.Trial registrationISRCTN39045408.

We determined the effects of conjugated linoleic acid (CLA) supplementation during resistance training. Seventy-six subjects were randomized to receive CLA (5 g.d(-1)) or placebo (PLA) for 7 wk while resistance training 3 d.wk(-1). Seventeen subjects crossed over to the opposite group for an additional 7 wk. Measurements at baseline, 7 wk, and 14 wk (for subjects in the crossover study) included body composition, muscle thickness of the elbow flexors and knee extensors, resting metabolic rate (RMR), bench and leg press strength, knee extension torque, and urinary markers of myofibrillar degradation (3-methylhistidine (3MH) and bone resorption (cross-linked N-telopeptides (Ntx)). After 7 wk the CLA group had greater increases in lean tissue mass (LTM) (+1.4 vs +0.2 kg; P < 0.05), greater losses of fat mass (-0.8 vs +0.4 kg; P < 0.05), and a smaller increase in 3MH (-0.1 vs + 1.3 micromol.kg LTM.d(-1); P < 0.05) compared with PLA. Changes between groups were similar for all other measurements, except for a greater increase in bench press strength for males on CLA (P < 0.05). In the crossover study subjects had minimal changes in body composition, but smaller increases in 3MH (-1.2 vs +2.2 micromol.kg LTM.d(-1); P < 0.01) and NTx (-4.8 vs +7.3 nmol.kg(-1) LTM.d(-1); P < 0.01) while on CLA versus PLA. Supplementation with CLA during resistance training results in relatively small changes in body composition accompanied by a lessening of the catabolic effect of training on muscle protein.

Age-related decrease in resting energy expenditure in sedentary white women: effects of regional differences in lean and fat mass

Acromegaly is associated with changes in body composition. Long-term changes following acromegaly treatment and the impact of different treatments have been less investigated. We performed a retrospective study in 201 patients with acromegaly. Body composition was assessed by dual-energy X-ray absorptiometry. To investigate the specific effects of treatment vs aging, changes in body composition were compared in one group of patients evaluated both at the time of active and controlled disease (active-to-controlled (A>C); n = 31) and in another group of patients evaluated two times while the disease was controlled (controlled-to-controlled (C>C); n = 32). In the whole cohort, insulin-like growth factor I (IGF-I) was correlated with fat (r = -0.369; P < 0.001) and lean mass (r = 0.383; P < 0.001). Patients from A>C and C>C groups were comparable for age, sex, BMI and follow-up duration (P = n.s.). Reduction in IGF-I levels was associated with an increase in fat mass and a decrease in lean mass in the A>C group, which was four and eight times more pronounced compared to the C>C group (fat mass: +39 ± 34% vs +10 ± 15%, P < 0.001; lean mass: -8 ± 8% vs -0.2 ± 6%, P < 0.001, respectively). Changes in fat mass were negatively associated with IGF-I (r = -0.450; P = 0.011) and independent of the individual therapy. The daily dose of pegvisomant correlated with fat mass (r = 0.421; P = 0.002) and insulin sensitivity index (r = -0.466; P < 0.001). Treatment of acromegaly strongly impacts body composition until biochemical disease remission, characterized by an increase in fat mass and a decrease in lean mass. These changes are closely associated with the normalization of IGF-I. Thereafter, body composition changes are similar to what is observed with aging.

Although the association between adipokines such as adiponectin, leptin, and body composition has been noted, whether they could predict the change of fat mass and lean body mass is unknown. We aimed to examine these associations in patients on peritoneal dialysis (PD) through a prospective cohort study. Body composition (by dual-energy x-ray absorptiometry) including fat mass and lean body mass were examined at baseline and then at year 3. Serum leptin and adiponectin levels were measured. Demographic data, comorbidity, biochemical data, inflammation (high-sensitive C-reactive protein [hs-CRP]) and insulin resistance (homeostatic model assessment [HOMA-IR]) were also examined. At baseline, serum adiponectin levels were significantly inversely correlated with weight, lean body mass index (LBMI), fat mass index (FMI), lean body mass (LBM), and fat mass (FM) in 213 prevalent patients. At year 3, FMI, LBMI, FM, and the percentage of FM (FM%) increased while the percentage of LBM (LBM%) significantly decreased despite unchanged weight and LBM among the remaining 112 patients. After adjustment for demographic data, comorbidities, hs-CRP, HOMA-IR, and daily energy intake (DEI), serum adiponectin at baseline was not associated with increases in LBMI, FMI, and FM, but independently associated with an increase in FM% and a decrease in LBM%. The predictive effect of high-serum adiponectin level on mortality disappeared after adjusting for diabetes and cardiovascular disease. Serum leptin was not associated with any changes in body composition during the follow-up, nor with the mortality in this cohort. A high adiponectin level could predict an increase in FM% and a decrease in LBM% during a 3-year follow-up in PD patients. Serum adiponectin could not independently predict mortality in PD patients.

Revisiting the obesity paradox: lean body mass, fat mass, and mortality in patients with atrial fibrillation

Maternal fat, but not lean, mass is increased among overweight/obese women with excess gestational weight gain

Because of the improved survival rate, both short term and long term adverse effects of breast cancer treatment have become increasingly important. Body weight and body composition before, during, and after chemotherapy may influence side effects during treatment and survival. The aims of this thesis were to assess among stage I-IIIB breast cancer patients: 1) the association between pre-treatment body composition and dose-limiting toxicities during chemotherapy, 2) potential changes in body weight and body composition during and after chemotherapy compared to changes in age-matched women without cancer in the same time period, and 3) dietary intake during chemotherapy compared to age-matched women without cancer in the same time period. Chapter 2 describes the association between pre-treatment body composition and dose-limiting toxicities during chemotherapy. Data from 172 breast cancer patients who participated in the COBRA-study were analysed. Body composition was measured using a total body Dual Energy X-ray Absorption (DEXA) scan. Information regarding dose-limiting toxicities was abstracted from medical records. A higher BMI (kg/m2) and a higher fat mass (kg and percentage) were associated with an increased risk of dose-limiting toxicity, while lean body mass (kg) was not associated with risk of toxicities. Chapter 3 presents the findings of a meta-analysis on changes in body weight during chemotherapy in breast cancer patients. The meta-analysis showed an overall gain in body weight of 2.7 kg (95% CI: 2.0-3.3) during chemotherapy, with a high degree of heterogeneity (I2= 94.2%). Weight gain in breast cancer patients was more pronounced in papers published before 2000 and studies including cyclophosphamide, methotrexate and 5-fluorouracil as chemotherapy regime. Chapter 4 describes changes in body weight and body composition during and after chemotherapy. Data from 145 patients and 121 women of an age-matched comparison group, participating in the COBRA-study were analysed. Body composition was measured using DEXA-scan at three time points during the study period. For the patient group, these tie points were: before start of chemotherapy, shortly after chemotherapy, and 6 months after chemotherapy. For the comparison group these measurements were conducted over a similar time frame: baseline, 6 months after baseline, and 12 months after baseline. In addition, we identified determinants of changes in body weight and body composition. Shortly after chemotherapy, patients had a significantly higher body weight, BMI, and lean body mass than women in the comparison group, while fat mass was similar. Six months after chemotherapy no differences in body weight or body composition were observed between the patient and comparison group. A younger age, better appetite during chemotherapy, and an ER-receptor negative tumour were associated with greater changes in body weight over time. A younger age and better appetite during chemotherapy were associated with greater changes in fat mass over time, while the only determinant associated with greater changes in lean body mass over time was a better appetite during chemotherapy. Chapter 5 describes the dietary intake and food groups before and during chemotherapy of breast cancer patients compared with women without cancer. In addition we assessed the association between symptoms and energy intake. Data from 117 breast cancer patients and 88 women without breast cancer who participated in the COBRA-study were used. Habitual dietary intake before chemotherapy was assessed using a food frequency questionnaire. Two 24-hr dietary recalls were used to assess actual dietary intake during chemotherapy for patients and within 6 months for the comparison group. Shortly after the 24-hr dietary recall, participants filled out questionnaires about symptoms. Before chemotherapy, dietary intake was similar for both groups. During chemotherapy, breast cancer patients reported significantly lower total energy, total fat, total protein, and alcohol intake than women without cancer, which could be explained by a lower intake of specific food groups. Overall results from this thesis suggest that pre-treatment fat mass is associated with dose-limiting toxicities during chemotherapy. Weight gain during chemotherapy appeared to be more modest than we expected based on literature and changes in body composition during chemotherapy consist mainly of an increase in lean body mass, which is only temporary and returned to baseline within 6 months after chemotherapy. A higher appetite during chemotherapy was associated with changes in body weight and body composition. A younger age at diagnosis was associated with greater changes in body weight and fat mass, but not with changes in lean body mass. In addition, an ER-receptor negative tumour was associated with greater changes in body weight, but not with changes in fat mass or lean body mass. During chemotherapy women with breast cancer have a lower intake of energy, fat, protein and alcohol compared to age-matched women without cancer, which was expressed in a lower intake of specific food groups. The results of this thesis do not suggest that dietary intake is associated with weight gain during chemotherapy.

Body composition and age in african-american and caucasian women: Relationship to plasma leptin levels

Body composition changes with age and sex differences become significant only after puberty. Boys and girls before the age of 8 yr do not differ in fat, lean or bone mineral mass. Hormonal influences during pubertal development determine the physiological adult male and female body composition phenotype. The aim of our study was to evaluate body composition changes due to central precocious puberty (PP) and the specific effects of therapy on these modifications. Sixteen patients (14 girls, 2 boys) were included in the study. They were diagnosed as affected by idiopathic PP according to standard hormonal and clinical criteria; anatomic alterations of hypothalamus-hypophysis region were excluded by MRI. Mean age at diagnosis was 5.9 +/- 1.9 yr. All patients received GnRH analog (Leuprolide or Triptorelin) treatment subcutaneously every 4 weeks for at least 1 yr. Mean period of treatment was 3.4 +/- 1.9 yr. Standard anthropometry and body composition analysis were performed at baseline and every 6-12 months. A group of healthy subjects with normal timing of puberty was matched (for age or for pubertal stage) served as the control group (CA or CP, respectively). Patients with PP showed at baseline a significant increase of BMI and relative body weight; lean and fat compartments were also increased but not significantly. During treatment, the PP group showed increased fat mass compared to CA (p<0.05), while no difference was found between PP and CP. Lean mass was similar to CA but lower than in CP (p<0.05). During treatment a significant increase in lean mass (both as total as well as limb mass) was observed. After stopping treatment there was no difference between PP and CP, except for lower lean mass (p<0.04). When puberty occurs precociously, lean and fat mass are not significantly different from age-matched control subjects. Data collected during treatment confirm a shortening of prepubertal lean mass development and the block of further lean mass development due to puberty itself, while fat mass accumulation continues. The net result of these modifications determines a typical body composition pattern in PP patients, after the end of therapy: lean mass is reduced by a shortening of the prepubertal growing period and by the "menopausal effect" of treatment itself. Fat mass is increased as a consequence of therapy and could lead to future obesity.

BackgroundWeight gain is one of the most feared patient-reported adverse event of glucocorticoids, however the effect of low-dose prednisolone on body weight and composition in RA still has to be...