Practical measurement of body composition using bioelectrical impedance, air displacement plethysmography and ultrasound in stable outpatients with short bowel syndrome receiving home parenteral nutrition: comparison of agreement between the methods.

BACKGROUND: People diagnosed with intestinal failure (IF) as a result of short bowel syndrome are dependent on home parenteral nutrition (HPN). Measuring nutritional status is essential for monitoring treatment. The present study aimed to determine the agreement and feasibility of three methods bioelectrical impedance analysis (BIA), ultrasound and air displacement plethysmography (ADP) for measuring body composition in people receiving HPN. METHODS: Body composition data were collected from patients attending an IF clinic. RESULTS: There were 50 participants recruited and data were collected for BIA (n = 46), ultrasound (n = 49) and ADP (n = 9). Numbers for ADP were much lower because of a lack of participant uptake. Fat-free mass (FFM) measured by BIA and ultrasound in comparison to ADP was found to have good intraclass correlation (ICC) 0.791 (95% confidence interval (CI) CI  -0.21 to 0.96) and a moderate ICC 0.659 [95% (CI) -0.27 to 0.92], respectively. Fat mass (FM) measured by both BIA and ultrasound in comparison to ADP was found to have moderate ICC 0.660 (95% CI -0.28 to 0.92) and poor ICC -0.005 (95% CI -0.73 to 0.65), respectively. CONCLUSIONS: Compared to ADP, BIA indicated moderate to good agreement for measuring body composition, whereas ultrasound indicated far less agreement, particularly when measuring FM. The lack of uptake of ADP suggests that participants found the Bodpod (COSMED Srl, Shepperton, UK) unfavourable. Considering that ultrasound has limited agreement and ADP was not the preferred option for participants, BIA shows some potential. However, the difference between ADP and BIA was larger for FM compared to FFM, which needs to be considered in the clinical setting.

Delay in estrogen commencement is associated with lower bone mineral density in Turner syndrome.

OBJECTIVE: Turner syndrome (TS) is associated with hypogonadism, osteoporosis and fractures. We investigated the prevalence and risk factors for low bone density and fractures in a TS cohort. METHODS: We included 76 TS patients (median age 28.5 years) attending a tertiary hospital between 1998 and 2015 who underwent dual-energy X-ray absorptiometry. Spine and femoral neck (FN) areal bone mineral density (aBMD) were compared with those of a control group. To adjust for smaller bone size, bone mineral apparent density (BMAD) was calculated. RESULTS: Primary amenorrhea was common (83%) in the TS cohort; the median age of pubertal induction was 15 years (range 11-30 years), and non-continuous estrogen therapy (ET) recorded in 40%. Almost one-third of TS patients reported fractures. TS patients had lower median spinal aBMD (1.026 g/cm2 vs. 1.221 g/cm2) and BMAD (0.156 g/cm3 vs. 0.161 g/cm3) than controls, and lower median FN aBMD (0.850 g/cm2 vs. 1.026 g/cm2) (all p < 0.01). More women with TS had spinal Z-score < -2.0 compared to controls (26.0% vs. 3.6%, p = 0.001). Spine and FN aBMD, BMAD and Z-scores were inversely associated with age commencing ET or years of estrogen deficiency. CONCLUSIONS: Delay in ET commencement was an independent risk factor for the lower bone density observed in women with TS. Early pubertal induction and ET compliance are important targets to optimize aBMD.

Patients with inflammatory bowel disease and their treating clinicians have different views regarding diet.

BACKGROUND: Diet and body composition play unclear roles in the pathogenesis, activity and symptoms of inflammatory bowel disease (IBD). Evidence-based guidance regarding dietary modification in IBD is lacking. We aimed to determine the attitudes of IBD patients and clinicians to diet. METHODS: The present cross-sectional study comprised an online questionnaire distributed to members of a national IBD patient organisation, assessing demographics, anthropometry, disease phenotype and dietary beliefs. Dietitians, gastroenterologists and surgeons were targeted for a similar questionnaire as a result of membership of national professional bodies. RESULTS: Nine hundred and twenty-eight patients (72.2% female; mean age 39.5 years; age range 5-91 years) responded. Two-thirds of the patients had Crohn's disease. The mean reported body mass index was 24.9 kg m-2 and was significantly skewed to the right. Patients who had taken >10 courses of steroids were had a greater probability of being overweight or obese, independent of disease complications. Most patients (71%) assumed that their diet affected their IBD; 61% considered their IBD specialist disregarded the importance of diet. Of the 136 clinicians who responded, the majority felt that diet was a factor in symptoms and intestinal microbiota. More gastroenterologists (44%) than dietitians (17%) considered that diet had a role in the pathogenesis of IBD (P = 0.003). Twenty-six percent of patients reported receiving dietary advice from their IBD specialist, whereas 98% of gastroenterologists reported advice provision. Patients received diverse advice. Half of the patients followed recommendations provided by a clinician. CONCLUSIONS: The present study demonstrates that IBD patients consider diet to be important in their disease. IBD clinicians from different disciplines have diverse views of the role of diet. Advice given to patients is heterogeneous, often perceived as inadequate and poorly followed.

Vastus medialis fat infiltration - a modifiable determinant of knee cartilage loss.

BACKGROUND: There is growing interest in the role of intramuscular fat and how it may influence clinical outcomes. Vastus medialis (VM) is a functionally important quadriceps muscle that helps to stabilise the knee joint. This longitudinal study examined the determinants of VM fat infiltration and whether VM fat infiltration influenced knee cartilage volume. METHODS: 250 participants without any diagnosed arthropathy were assessed at baseline between 2005 and 2008, and 197 participants at follow-up between 2008 and 2010. Ambulatory and sporting activity were assessed and magnetic resonance imaging (MRI) was used to determine knee cartilage volume and VM fat infiltration. RESULTS: Age, female gender, BMI and weight were positively associated with baseline VM fat infiltration (P ≤ 0.03), while ambulatory and sporting activity were negatively associated with VM fat infiltration (P ≤ 0.05). After adjusting for confounders, a reduction in VM fat infiltration was associated with a reduced annual loss of medial tibial (ß = -10 mm(3); 95% CI -19 to 0 mm(3); P = 0.04) and patella (ß = -18 mm(3); 95% CI -36 to 0 mm(3); P = 0.04) cartilage volume. CONCLUSION: This community-based study of healthy adults has shown that VM fat infiltration can be modified by lifestyle factors including weight loss and exercise, and reducing fat infiltration in VM has beneficial effect on knee cartilage preservation. The findings suggest that modifying VM fat infiltration via lifestyle interventions may have the potential to reduce the risk of knee OA.

Clinical selection criteria can predict futile intervention in patients referred for percutaneous endoscopic gastrostomy insertion.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) placement is performed in a patient group with high mortality in the short and medium term. For a significant proportion of patients, the procedure provides no increase in survival. There are no standardised assessment tools available to determine the clinical appropriateness of PEG placement, nor any to predict clinical outcome. AIM: The study aims to determine whether clinical assessment, by a trained dietitian, of the appropriateness of PEG placement is predictive of mortality in the short and medium terms. METHODS: A prospective audit was undertaken of all requests for PEG placement at a single large, publicly funded Australian tertiary hospital. The clinical appropriateness of each request was assessed by a trained dietitian, and data on age, sex, reason for referral, comorbidities and satisfaction of assessment criteria were collected, and patient outcome and survival were compared for all patients according to whether a PEG was inserted or not. Main outcome measures were mortality at 30 and 150 days after referral. RESULTS: During the period 2005-2008, 198 patients were referred for PEG; 94 were assessed as appropriate referrals, 104 as inappropriate. Eighty-four patients who underwent gastrostomy, after being assessed as appropriate, had significantly reduced mortality at 30 days (96.4% vs 74.6%, P < 0.0001) and 150 days (82.1% vs 57.9%, P = 0.0001) compared with all other patients. Patients who received PEG despite contrary advice had no significant survival advantage, at 30 days or 150 days, over patients who did not receive PEG. CONCLUSION: The application of selection criteria by trained assessors improves patient selection for PEG insertion and predicts mortality at early and later time points, by identifying patients unlikely to benefit from PEG. The group of patients who received a gastrostomy despite an adverse assessment had no mortality benefit - in these patients, the procedure may have been futile.

The effect of gonadal status on body composition and bone mineral density in transfusion-dependent thalassemia.

UNLABELLED: Patients with transfusion-dependent thalassemia have abnormal growth, hormonal deficits, and increased bone loss. We investigated the relationship between skeletal muscle mass, fat mass, and bone mineral density in adult subjects with transfusion-dependent thalassemia based on their gonadal status. Our findings show that hypogonadism attenuates the strength of the muscle-bone relationship in males but strengthens the positive correlation of skeletal muscle mass and fat mass in female subjects. INTRODUCTION: Transfusion-dependent thalassemia is associated with a high prevalence of fractures. Multiple hormonal complications, in particular hypogonadism, can lead to changes in body composition and bone mineral density (BMD). We investigated for the first time the relationship between skeletal muscle mass (SMM), fat mass, and BMD in adult subjects with transfusion-dependent thalassemia based on their gonadal status. METHODS: A retrospective cohort study of 186 adults with transfusion-dependent thalassemia was analyzed. Body composition and BMD were measured using dual energy X-ray absorptiometry. The association between skeletal muscle, fat, and BMD was investigated through uni-, multi-, and stepwise regression analyses after adjusting for multicollinearity. SMM was derived using the formula, SMM = 1.19 × ALST-1.65, where ALST is equivalent to the sum of both arm and leg lean tissue mass. RESULTS: There were 186 subjects, males (43.5 %) and females (56.5 %), with a median age of 36.5. Hypogonadism was reported in 44.4 % of males and 44.7 % of females. SMM and BMD were positively correlated and strongest in eugonadal males (0.36 ≤ R (2) ≤ 0.59), but the association was attenuated in hypogonadal males. SMM (0.27 ≤ R (2) ≤ 0.69) and total fat mass (0.26 ≤ R (2) ≤ 0.55) were positively correlated with BMD in hypogonadal females, but the correlation was less pronounced in eugonadal females. Leg lean tissue mass and arm lean tissue mass in males and females, respectively, were most highly correlated to BMD in the stepwise regression analysis. CONCLUSION: Hypogonadism attenuates the strength of the muscle-bone relationship in males but strengthens the positive correlation of skeletal muscle mass and fat mass in female subjects. This study supports the notion that exercise is important for maintaining BMD and the need to optimize treatment of hypogonadism in patients with transfusion-dependent thalassemia.

Thalassemia bone disease: the association between nephrolithiasis, bone mineral density and fractures.

UNLABELLED: Thalassemia bone disease is well described, but the prevalence of nephrolithiasis has not been characterized. The association between nephrolithiasis, reduced bone density, and increased fractures has been demonstrated through this retrospective study of 166 participants with transfusion-dependent thalassemia. The findings support the need for increased vigilance of kidney and bone disease in this cohort. INTRODUCTION: Previous studies have revealed that thalassemia is associated with reduced bone mineral density (BMD) and fractures. Many causes are implicated including hypogonadism, growth hormone deficiency, marrow expansion, and iron overload. Nephrolithiasis is associated with reduced BMD and increased fractures in the general population. However, the prevalence of nephrolithiasis and its association with bone density and fractures have not been characterized in thalassemia. METHODS: We have addressed this question by performing a retrospective cohort study of 166 participants with transfusion-dependent thalassemia who had undergone dual-energy X-ray absorptiometry between 2009 and 2011. Logistic regression modeling was used to adjust for potential confounders. RESULTS: We found a high prevalence of kidney stones (18.1 %) which was greater in males compared to females (28.7 vs 9.7 %, respectively). Renal stones were associated with reduced femoral neck Z-score and fractures in men after adjusting for potential confounders. These results indicate that nephrolithiasis is highly prevalent in patients with transfusion-dependent thalassemia and is significantly associated with reduced BMD and increased fractures. CONCLUSIONS: The findings from this study strongly support the need for ongoing surveillance of BMD, fractures, and nephrolithiasis in the management of transfusion-dependent thalassemia.

Effect of exercise training on insulin sensitivity, mitochondria and computed tomography muscle attenuation in overweight women with and without polycystic ovary syndrome.

AIMS/HYPOTHESIS: Polycystic ovary syndrome (PCOS) is an insulin resistant (IR) state. Increased skeletal muscle lipid content and impaired mitochondrial biogenesis have been implicated in the pathogenesis of IR. We investigated whether differences in these variables explain the IR of women affected by PCOS and whether improvements in IR with exercise are reflected by changes in these variables. METHODS: Sixteen PCOS and 13 non-PCOS overweight women were assessed, and eight PCOS and seven non-PCOS women were reassessed after 12 weeks of moderate and vigorous exercise training. Outcomes included insulin sensitivity (glucose infusion rate [GIR]), skeletal muscle gene expression and protein abundance, enzyme activity of selected mitochondrial components, and computed tomography (CT) attenuation-estimated muscle lipid. RESULTS: GIR was lower in women with PCOS versus those without (p = 0.01) and increased with exercise in both groups. Baseline CT muscle attenuation suggested a trend to less muscle lipid in PCOS, which increased with exercise training, with a difference in the change in muscle lipid (p = 0.01, age-corrected), compared with non-PCOS women. GIR correlated with PGC1A gene expression across the whole group; skeletal muscle expression of mitochondrial biogenesis markers was not different between groups at baseline, or after training. Neither lipid changes nor mitochondrial changes correlated with changes in GIR. CONCLUSIONS/INTERPRETATION: Differences in IR in women with and without PCOS were not explained by differences in skeletal muscle lipid or mitochondrial parameters. Improvements in IR with exercise were dissociated from mitochondrial parameters. CT muscle attenuation suggested a differential capacity of PCOS muscle to store lipid compared with non-PCOS. TRIAL REGISTRATION: Clinicaltrials.gov ISRCTN84763265. FUNDING: National Health & Medical Research Council (Grant number 606553), Monash University and The Jean Hailes Foundation.

Increase in visceral and subcutaneous abdominal fat in men with prostate cancer treated with androgen deprivation therapy.

OBJECTIVE: Androgen deprivation therapy (ADT) for prostate cancer is associated with increases in fat mass and risk of type 2 diabetes; however, the relationship between sex steroid deficiency and abdominal fat distribution remains controversial. DESIGN: We conducted a 12-month prospective observational study at a tertiary referral centre. PATIENTS AND MEASUREMENTS: We investigated changes in abdominal fat distribution and insulin resistance in 26 men (70.6±6.8 years) with nonmetastatic prostate cancer during the first year of ADT. RESULTS: Twelve months of ADT increased visceral abdominal fat area by 22% (from 160.8±61.7 to 195.9±69.7 cm(2) ; P<0.01) and subcutaneous abdominal fat area by 13% (from 240.7±107.5 to 271.3±92.8 cm(2) ; P<0.01). Fat mass increased by 14% (+3.4 kg; P<0.001) and lean tissue mass decreased by 3.6% (-1·9 kg; P<0.001). Insulin resistance (HOMA-IR) increased by 12% (2.50±1.12 to 2.79±1.31, P<0.05). There was no change in fasting glucose or glycated haemoglobin levels. Total testosterone (TT) was inversely associated with visceral fat area independent of oestradiol (E2), but E2 was not associated with visceral fat area independent of TT. Visceral fat area, not TT or E2, was independently associated with insulin resistance. CONCLUSIONS: ADT for prostate cancer results in accumulation of both visceral and subcutaneous abdominal fat. Increased visceral fat area appears more closely linked to testosterone than oestradiol deficiency. Increased insulin resistance may arise secondary to visceral fat accumulation, rather than as a direct result of sex steroid deficiency.

Variability in total testosterone levels in ageing men with symptoms of androgen deficiency.

The aim of this study was to determine the variability in total testosterone (TT) levels in healthy, non-obese ageing men with symptoms of androgen deficiency. Men aged ≥55 years were recruited from the community. Morning TT levels were measured on four occasions in a 12-month period. In all, 96 men aged 62.7 ± 6.8 years were studied. Geometric mean values (95% confidence interval) of TT levels for the cohort at each time point were 14.5 (13.4-15.7), 14.6 (13.5-15.8), 15.5 (14.4-16.8) and 15.0 (13.9-16.2) nmol/L. The maximum intra-individual difference in TT between the four samples was 4.1 nmol/L (interquartile range: 2.9-6.4). Using the average of two baseline TT values reduces the maximum difference to 2.3 nmol/L (1.0-3.8). Only 1 of 25 men with a documented TT <10 nmol/L at baseline had TT levels <10 nmol/L at all subsequent time points. A single TT level is a reliable predictor of repeat measures taken within a 12-month period for a cohort of healthy ageing men with symptoms of androgen deficiency. However, given that the diagnostic criteria for androgen deficiency are, in part, predicated upon serum TT, there is sufficient intra-subject variability to warrant repeat sampling to confirm an initial low TT level. Using an average of two baseline TT values reduces this variability.

Exercise decreases anti-müllerian hormone in anovulatory overweight women with polycystic ovary syndrome: a pilot study.

Polycystic ovary syndrome (PCOS) is a common condition in women associated with menstrual irregularity and anovulation. While obesity worsens and weight loss or exercise improves reproduction function in PCOS, the mechanism for this is unclear. The aim of this study was to examine the effect of exercise on ovarian hormones [anti-Müllerian hormone (AMH)] and menstrual and ovulatory function in women with and without PCOS. Overweight women with (n=7) and without (n=8) PCOS of comparable age, weight and BMI undertook a 12-week intensified endurance exercise training program (1 h 3 times/week) with no structured energy restriction. Primary outcomes were AMH, ovulation (weekly urinary pregnanediol) and menstrual regularity. Secondary outcomes were insulin resistance (euglycemic hyperinsulinemic clamp) and body composition (computed tomography and dual X-ray absorptiometry). Exercise decreased BMI, total and android fat mass and improved insulin sensitivity for all women. AMH was significantly higher in women with PCOS compared to controls before (p<0.001) and after exercise (p=0.001). There was a significant interaction between AMH changes with exercise and PCOS status (p=0.007) such that women without PCOS had no change in AMH (+1.4±5.2 pmol/l, p=0.48) while women with PCOS had a decrease in AMH (- 13.2±11.7 pmol/l, p=0.025). Exercise is associated with improvements in ovarian hormones in women with abnormal ovarian function. This suggests that mechanisms associated with ovarian dysfunction can be improved by exercise in PCOS.

Exercise and insulin resistance in PCOS: muscle insulin signalling and fibrosis.

OBJECTIVE: Mechanisms of insulin resistance in polycystic ovary syndrome (PCOS) remain ill defined, contributing to sub-optimal therapies. Recognising skeletal muscle plays a key role in glucose homeostasis we investigated early insulin signalling, its association with aberrant transforming growth factor ß (TGFß)-regulated tissue fibrosis. We also explored the impact of aerobic exercise on these molecular pathways. METHODS: A secondary analysis from a cross-sectional study was undertaken in women with (n = 30) or without (n = 29) PCOS across lean and overweight BMIs. A subset of participants with (n = 8) or without (n = 8) PCOS who were overweight completed 12 weeks of aerobic exercise training. Muscle was sampled before and 30 min into a euglycaemic-hyperinsulinaemic clamp pre and post training. RESULTS: We found reduced signalling in PCOS of mechanistic target of rapamycin (mTOR). Exercise training augmented but did not completely rescue this signalling defect in women with PCOS. Genes in the TGFß signalling network were upregulated in skeletal muscle in the overweight women with PCOS but were unresponsive to exercise training except for genes encoding LOX, collagen 1 and 3. CONCLUSIONS: We provide new insights into defects in early insulin signalling, tissue fibrosis, and hyperandrogenism in PCOS-specific insulin resistance in lean and overweight women. PCOS-specific insulin signalling defects were isolated to mTOR, while gene expression implicated TGFß ligand regulating a fibrosis in the PCOS-obesity synergy in insulin resistance and altered responses to exercise. Interestingly, there was little evidence for hyperandrogenism as a mechanism for insulin resistance.

Weight loss with liraglutide, a once-daily human glucagon-like peptide-1 analogue for type 2 diabetes treatment as monotherapy or added to metformin, is primarily as a result of a reduction in fat tissue.

AIM: The effect on body composition of liraglutide, a once-daily human glucagon-like peptide-1 analogue, as monotherapy or added to metformin was examined in patients with type 2 diabetes (T2D). METHODS: These were randomized, double-blind, parallel-group trials of 26 [Liraglutide Effect and Action in Diabetes-2 (LEAD-2)] and 52 weeks (LEAD-3). Patients with T2D, aged 18-80 years, body mass index (BMI) < or =40 kg/m(2) (LEAD-2), < or =45 kg/m(2) (LEAD-3) and HbA1c 7.0-11.0% were included. Patients were randomized to liraglutide 1.8, 1.2 or 0.6 mg/day, placebo or glimepiride 4 mg/day, all combined with metformin 1.5-2 g/day in LEAD-2 and to liraglutide 1.8, 1.2 or glimepiride 8 mg/day in LEAD-3. LEAD-2/3: total lean body tissue, fat tissue and fat percentage were measured. LEAD-2: adipose tissue area and hepatic steatosis were assessed. RESULTS: LEAD-2: fat percentage with liraglutide 1.2 and 1.8 mg/metformin was significantly reduced vs. glimepiride/metformin (p < 0.05) but not vs. placebo. Visceral and subcutaneous adipose tissue areas were reduced from baseline in all liraglutide/metformin arms. Except with liraglutide 0.6 mg/metformin, reductions were significantly different vs. changes seen with glimepiride (p < 0.05) but not with placebo. Liver-to-spleen attenuation ratio increased with liraglutide 1.8 mg/metformin possibly indicating reduced hepatic steatosis. LEAD-3: reductions in fat mass and fat percentage with liraglutide monotherapy were significantly different vs. increases with glimepiride (p < 0.01). CONCLUSION: Liraglutide (monotherapy or added to metformin) significantly reduced fat mass and fat percentage vs. glimepiride in patients with T2D.

Testosterone therapy prevents gain in visceral adipose tissue and loss of skeletal muscle in nonobese aging men.

BACKGROUND: Trials of testosterone therapy in aging men have demonstrated increases in fat-free mass (FFM) and skeletal muscle and decreases in fat mass (FM) but have not reported the impact of baseline body composition. OBJECTIVE: The objective of the study was to determine the effect, in nonobese aging men with symptoms of androgen deficiency and low-normal serum testosterone levels, of testosterone therapy on total and regional body composition and hormonal and metabolic indices. METHODS: Sixty healthy but symptomatic, nonobese men aged 55 yr or older with total testosterone (TT) levels less than 15 nm were randomized to transdermal testosterone patches or placebo for 52 wk. Body composition, by dual-energy x-ray absorptiometry (FM, FFM, skeletal muscle) and magnetic resonance imaging (abdominal sc and visceral adipose tissue, thigh skeletal muscle, and intermuscular fat) and hormonal and metabolic parameters were measured at wk 0 and 52. RESULTS: Serum TT increased by 30% (P = 0.01), and LH decreased by 50% (P < 0.001). Relative to placebo, total body FFM (P = 0.03) and skeletal muscle (P = 0.008) were increased and thigh skeletal muscle loss was prevented (P = 0.045) with testosterone therapy and visceral fat accumulation decreased (P = 0.001) without change in total body or abdominal sc FM; change in visceral fat was correlated with change in TT levels (r2 = 0.36; P = 0.014). There was a trend to increasing total and low-density lipoprotein cholesterol with placebo. CONCLUSION: Testosterone therapy, relative to placebo, selectively lessened visceral fat accumulation without change in total body FM and increased total body FFM and total body and thigh skeletal muscle mass. Further studies are needed to determine the impact of these body compositional changes on markers of metabolic and cardiovascular risk.

Dietary flour supplementation decreases post-menopausal hot flushes: effect of soy and wheat.

Plants contain compounds with oestrogen--like action called phytoestrogens. Soy contains daidzin, a potent phytoestrogen, and wheat flour contains less potent enterolactones. We aimed to show in 58 postmenopausal women (age 54, range 30-70 years) with at least 14 hot flushes per week, that their daily diet supplemented with soy flour (n = 28) could reduce flushes compared with wheat flour (n = 30) over 12 weeks when randomised and double blind. Hot flushes significantly decreased in the soy and wheat flour groups (40% and 25% reduction, respectively < 0.001 for both) with a significant rapid response in the soy flour group in 6 weeks (P < 0.001) that continued. Menopausal symptom score decreased significantly in both groups (P < 0.05). Urinary daidzein excretion confirmed compliance. Vaginal cell maturation, plasma lipids and urinary calcium remained unchanged. Serum FSH decreased and urinary hydroxyproline increased in the wheat flour group.

Body composition, metabolic syndrome and testosterone in ageing men.

The ageing process in men is marked by changes in body composition (loss of fat-free mass (FFM) and skeletal muscle, and gain in fat mass (FM)) and is associated with a decline in serum testosterone. Correlations between these aspects of ageing and the acknowledged role of exogenous testosterone in reversing the loss of FFM and gain in FM seen in adult men with congenital or acquired hypoandrogenism have led to the hypothesis that testosterone therapy in ageing men will result in favourable changes in body composition and may improve metabolic status and/or cardiovascular risk. Data from randomized controlled trials of testosterone therapy in ageing men addressing the endpoints of body composition and components of the metabolic syndrome and cardiovascular risk factors are reviewed, and the impact of the increasing prevalence of obesity on these relationships is considered.

Low muscle mass at initiation of anti-TNF therapy for inflammatory bowel disease is associated with early treatment failure: a retrospective analysis.

BACKGROUND/OBJECTIVES: Delayed treatment failure occurs in a significant proportion of inflammatory bowel disease (IBD) patients treated with tumor necrosis factor-alpha (TNF) antagonists. Identification of predictors of loss of response (LOR) may help to optimize therapy. We sought to determine whether body composition parameters at the commencement of anti-TNF therapy were associated with earlier treatment failure. SUBJECTS/METHODS: A retrospective cohort study was performed on 68 patients who had undergone cross-sectional abdominal imaging coincident with the commencement of anti-TNF drugs. Analysis of the images at the third lumbar vertebra was performed using standard techniques to determine cross-sectional areas of skeletal muscle (SM), visceral adipose tissue, subcutaneous adipose tissue and intermuscular adipose tissue. Treatment failure was defined as: post-induction hospital admission or surgery for IBD, escalation of TNF dose or immunosuppressants for clinical LOR, emergence of a new fistula or Crohn's Disease Activity Index (CDAI) >150. RESULTS: Two-thirds of patients had myopenia. Patients with less than gender-specific median SM area had a median time to failure of 520 (s.d. 135) days compared to 1100 (s.d. 151) days for those with more than median SM area (P=0.036). No difference was found in disease duration, inflammatory markers or CDAI between quartiles of SM area. No relation between outcomes and measures of adipose tissue, weight or body mass index was observed. CONCLUSIONS: Identifying low muscle mass at anti-TNF induction as a risk factor for treatment failure may contribute to a more tailored approach to IBD therapy.

Visceral adiposity predicts post-operative Crohn's disease recurrence.

BACKGROUND: Excessive visceral adipose tissue has been associated with poorer outcomes in patients with inflammatory bowel disease. AIM: To determine whether body composition is associated with outcome in a prospective study of post-operative Crohn's disease patients. METHODS: The POCER study evaluated management strategies for prevention of post-operative Crohn's disease recurrence; subjects were enrolled after resection of all macroscopic Crohn's disease and were randomised to early endoscopy and possible treatment escalation, or standard care. The primary endpoint was endoscopic recurrence at 18 months. 44 subjects with cross-sectional abdominal imaging were studied, and body composition analysis performed using established techniques to measure visceral adipose tissue area, subcutaneous adipose tissue area, and skeletal muscle area. RESULTS: The body composition parameter with the greatest variance was visceral adipose tissue. Regardless of treatment, all subjects with visceral adipose tissue/height2 >1.5 times the gender-specific mean experienced endoscopic recurrence at 18 months (compared to 47%) [relative risk 2.1, 95% CI 1.5-3.0, P = 0.012]. Waist circumference correlated strongly with visceral adipose tissue area (ρ = 0.840, P < 0.001). Low skeletal muscle was prevalent (41% of patients), but did not predict endoscopic recurrence; however, appendicular skeletal muscle indices correlated inversely with faecal calprotectin (ρ = 0.560, P = 0.046). CONCLUSIONS: Visceral adiposity is an independent risk factor for endoscopic recurrence of Crohn's disease after surgery. Sarcopenia correlates with inflammatory biomarkers. Measures of visceral adipose tissue may help to stratify risk in post-operative management strategies.

Comparison of Australian and international guidelines for grading severity of chronic obstructive pulmonary disease.

AIM: To compare grading of chronic obstructive pulmonary disease (COPD) using Australian guidelines Confirm diagnosis, Optimize function, Prevent deterioration, Develop a self-management plan and manage eXacerbations (COPD-X) versus Global initiative for Obstructive Lung Disease (GOLD) guidelines and to assess whether this is associated with differences in other health domains affected by COPD. Adult outpatients (n = 61) with COPD were studied using lung function measurements, six-minute walk test and body composition assessments. Subjects also completed self-rated dyspnoea scores and health-related quality-of-life scales. For each patient, COPD severity was graded using both COPD-X and GOLD guidelines, and results were collectively analysed. If significant discrepancies were observed, comparisons of other health domains were carried out. After grading severity using COPD-X and GOLD guidelines, significant discrepancies were noted. Of nine subjects with no disease (normal) based on COPD-X, seven were judged to be 'mild' according to GOLD. Similarly, 11 of 12 patients with mild disease (COPD-X) had 'moderate' disease judged by GOLD, and 9 of 23 with moderate severity (COPD-X) had 'severe' COPD using GOLD. Finally, 6 of 17 patients with COPD-X-rated severe disease had 'very severe' disease using the GOLD criteria. Among patients with COPD-X severe disease, those with GOLD discordant (very severe) severity had a poorer quality of life compared with those with GOLD concordant (severe) severity (P = 0.006). Similarly, there was also a trend towards lower six-minute walk test distance and greater subjective dyspnoea in GOLD very severe patients compared with GOLD severe patients. Significant discrepancies in grading of severity exist between Australian and international COPD guidelines. Current Australian guidelines for severity grading may not fully reflect the effect COPD has on other key domains of health.

Musculoskeletal and Endocrine Health in Adults With Cerebral Palsy: New Opportunities for Intervention.

CONTEXT: Cerebral palsy (CP) increases fracture risk through diminished ambulation, nutritional deficiencies, and anticonvulsant medication use. Studies examining bone mineral density (BMD) in adults with CP are limited. OBJECTIVE: To examine the relationship between body composition, BMD, and fractures in adults with CP. The effect of functional, nutritional, and endocrine factors on BMD and body composition is also explored. DESIGN: Retrospective cross-sectional study. SETTING AND PARTICIPANTS: Forty-five adults with CP (mean age, 28.3 ± 11.0 years) who had dual-energy x-ray absorptiometry imaging at a single tertiary hospital between 2005 and 2015. RESULTS: Seventeen (38%) had a past history of fragility fracture; 43% had a Z-score of ≤ -2.0 at the lumbar spine (LS) and 41% at the femoral neck (FN). In nonambulatory patients, every one unit decrease in FN Z-score increased the risk of fracture 3.2-fold (95% confidence interval, 1.07-9.70; P = .044). Stepwise linear regression revealed that the Gross Motor Function Classification System was the best predictor of LS Z-score (R(2) = 0.550; ß = -0.582; P = .002) and FN Z-score (R(2) = 0.428; ß = -0.494; P = .004); 35.7% of the variance in BMD was accounted for by lean tissue mass. Hypogonadism, present in 20% of patients, was associated with reduced lean tissue mass and reduced LS BMD. Lean tissue mass positively correlated with BMD in eugonadal patients, but not in hypogonadal patients. CONCLUSIONS: Low BMD and fractures are common in adults with CP. This is the first study to document hypogonadism in adults with CP with detrimental changes in body composition and BMD.