Liraglutide and cardiovascular outcomes in adults with overweight or obesity: A post hoc analysis from SCALE randomized controlled trials.

The cardiovascular safety of liraglutide, a glucagon-like peptide-1 receptor agonist approved for weight management at a dose of 3.0 mg, was evaluated post hoc using data from 5908 participants in 5 randomized, double-blind, placebo-controlled clinical trials. Participants were randomized to liraglutide or a comparator group (placebo or orlistat). The objective was to evaluate whether cardiovascular risk was increased with liraglutide treatment. The primary composite outcome of this time-to-event analysis was the first occurrence of cardiovascular death, nonfatal myocardial infarction or nonfatal stroke. These cardiovascular events were adjudicated prospectively for three of the trials and retrospectively for two trials by an event adjudication committee. The primary outcome was analyzed using a Cox proportional hazards model, stratified by trial. With liraglutide 3.0 mg, 8 participants had positively adjudicated cardiovascular events (1.54 events/1000 person-years) compared to 10 participants in the comparators group (3.65 events/1000 person-years). The hazard ratio for liraglutide 3.0 mg compared to comparators was 0.42 (95% confidence interval, 0.17-1.08). In this analysis, liraglutide 3.0 mg treatment was not associated with excess cardiovascular risk. However, the wide confidence intervals and retrospective adjudication of events in two of the trials are limitations of the analysis.

Changes in body weight and pulse: outcome events in overweight and obese subjects with cardiovascular disease in the SCOUT trial.

BACKGROUND/OBJECTIVES: The Sibutramine Cardiovascular OUTcomes (SCOUT) trial showed a significantly increased relative risk of nonfatal cardiovascular events, but not mortality, in overweight and obese subjects receiving long-term sibutramine treatment with diet and exercise. We examined the relationship between early changes (both increases and decreases) in pulse rate, and the impact of these changes on subsequent cardiovascular outcome events in both the placebo and sibutramine groups. SUBJECTS/METHODS: 9804 males and females, aged ⩾55 years, with a body mass index of 27-45 kg m(-)(2) were included in this current subanalysis of the SCOUT trial. Subjects were required to have a history of cardiovascular disease and/or type 2 diabetes mellitus with at least one cardiovascular risk factor, to assess cardiovascular outcomes. The primary outcome event (POE) was a composite of nonfatal myocardial infarction, nonfatal stroke, resuscitated cardiac arrest or cardiovascular death. Time-to-event analyses of the POE were performed using Cox regression models. RESULTS: During the initial 6-week sibutramine treatment period, the induced pulse rate increase was related to weight change (1.9±7.7 beats per minute (bpm) with weight increase; 1.4±7.3 bpm, 0-5 kg weight loss; 0.6±7.4 bpm, ⩾5 kg weight loss). Throughout the subsequent treatment period, those continuing on sibutramine showed a consistently higher mean pulse rate than the placebo group. There was no difference in POE rates with either an increase or decrease in pulse rate over the lead-in period, or during lead-in baseline to 12 months post randomization. There was also no relationship between pulse rate at lead-in baseline and subsequent cardiovascular events in subjects with or without a cardiac arrhythmia. CONCLUSION: Baseline pulse rate and changes in pulse rate may not be an important modifier nor a clinically useful predictor of outcome in an individual elderly cardiovascular obese subject exposed to weight management.

Cost effectiveness of primary care referral to a commercial provider for weight loss treatment, relative to standard care: a modelled lifetime analysis.

BACKGROUND: Because of the high prevalence of overweight and obesity, there is a need to identify cost-effective approaches for weight loss in primary care and community settings. OBJECTIVE: To evaluate the long-term cost effectiveness of a commercial weight loss programme (Weight Watchers) (CP) compared with standard care (SC), as defined by national guidelines. METHODS: A Markov model was developed to calculate the incremental cost-effectiveness ratio (ICER), expressed as the cost per quality-adjusted life year (QALY) over the lifetime. The probabilities and quality-of-life utilities of outcomes were extrapolated from trial data using estimates from the published literature. A health sector perspective was adopted. RESULTS: Over a patient's lifetime, the CP resulted in an incremental cost saving of AUD 70 per patient, and an incremental 0.03 QALYs gained per patient. As such, the CP was found to be the dominant treatment, being more effective and less costly than SC (95% confidence interval: dominant to 6225 per QALY). Despite the CP delaying the onset of diabetes by ∼10 months, there was no significant difference in the incidence of type 2 diabetes, with the CP achieving <0.1% fewer cases than SC over the lifetime. CONCLUSION: The modelled results suggest that referral to community-based interventions may provide a highly cost-effective approach for those at high risk of weight-related comorbidities.

The challenge of a 2-year follow-up after intervention for weight loss in primary care.

BACKGROUND: Many weight loss programmes show short-term success, but long-term data in larger studies are scarce, especially in community settings. Attrition is common and complicates the interpretation of long-term outcomes. OBJECTIVE: To investigate 2-year outcomes and explore issues of attrition and missing data. SUBJECTS: A total of 772 overweight and obese adults recruited by primary care practices in Australia, Germany and the UK and randomised to a 12-month weight loss intervention delivered in a commercial programme (CP) or in standard care (SC). MEASUREMENT: Weight change from 0-24 and 12-24 months including measured weights only and measured and self-reported weights, using last observation carried forward (LOCF), baseline observation carried forward (BOCF), completers-only and missing-at-random (MAR) analyses. RESULTS: A total of 203 participants completed the 24-month visit. Using measured weights only, there was a trend for greater 24-month weight loss in CP than in SC, but the difference was only statistically significant in the LOCF and BOCF analyses: LOCF: -4.14 vs -1.99 kg, difference adjusted for centre -2.08 kg, P<0.001; BOCF: -1.33 vs -0.74 kg, adjusted difference -0.60 kg, P=0.032; completers: -4.76 vs -2.99 kg, adjusted difference -1.53 kg, P=0.113; missing at random: -3.00 vs -1.94 kg, adjusted difference -1.04 kg, P=0.150. Both groups gained weight from 12-24 months and weight regain was significantly (P<0.001) greater for CP than for SC in all analysis approaches. Inclusion of self-reported weights from a further 138 participants did not change the interpretation of the findings. CONCLUSION: Initial weight loss was poorly maintained during the no-intervention follow-up, but both groups did have lower weight over the 24 months. Attrition was high in both groups, and assumptions about missing data had considerable impact on the magnitude and statistical significance of treatment effects. It is vital that trials on weight loss interventions consider the plausibility of these differences in an analytical approach when interpreting research findings and comparing data between studies.

Changes in body weight and blood pressure: paradoxical outcome events in overweight and obese subjects with cardiovascular disease.

BACKGROUND/OBJECTIVES: The Sibutramine Cardiovascular OUTcomes (SCOUT) trial showed a significantly increased relative risk of nonfatal cardiovascular events, but not mortality, in overweight and obese subjects receiving long-term sibutramine treatment with diet and exercise. We examined the relationship between early changes (both increases and decreases) in body weight and blood pressure, and the impact of these changes on subsequent cardiovascular outcome events. SUBJECTS/METHODS: A total of 9804 male and female subjects, aged 55 years or older, with a body mass index of 27-45 kg m(-2) were included in this current subanalysis of the SCOUT trial. Subjects were required to have a history of cardiovascular disease and/or type 2 diabetes mellitus with at least one cardiovascular risk factor (hypertension, dyslipidemia, current smoking or diabetic nephropathy) to assess cardiovascular outcomes. Post hoc subgroup analyses of weight change (categories) and blood pressure were performed overall and by treatment group (6-week sibutramine followed by randomized placebo or continued sibutramine). The primary outcome event (POE) was a composite of nonfatal myocardial infarction, nonfatal stroke, resuscitated cardiac arrest or cardiovascular death. Time-to-event analyses of the POE were performed using Cox regression models with factors for treatment, subgroups and interactions. RESULTS: During the initial 6-week sibutramine treatment period, systolic blood pressure decreased progressively with increasing weight loss in hypertensive subjects (-8.1±10.5 mm Hg with <5 kg weight loss to -10.8±11.0 mm Hg with ⩾5 kg weight loss). The highest POE incidence occurred mainly in groups with increases in both weight and blood pressure. However, with long-term sibutramine treatment, a markedly lower blood pressure tended to increase POEs. CONCLUSION: Modest weight loss and modest lower blood pressure each reduced the incidence of cardiovascular events, as expected. However, the combination of early marked weight loss and rapid blood pressure reduction seems to be harmful in this obese elderly cardiovascular diseased population.

Association between serum bilirubin and cardiovascular disease in an overweight high risk population from the SCOUT trial.

BACKGROUND AND AIMS: An inverse relationship between (serum) total bilirubin and risk of cardiovascular disease has been reported previously, but longitudinal data on overweight and obese patients are lacking. We have investigated the relationship between total bilirubin and cardiovascular adverse events in a large group of patients with risk factors for cardiovascular disease who were enrolled in a large weight loss trial. METHODS AND RESULTS: Data from the Sibutramine Cardiovascular Outcomes (SCOUT) trial, including almost 10.000 overweight/obese high cardiovascular risk patients, were used. The relationship between total bilirubin level at screening and the primary outcome (i.e. non-fatal myocardial infarction, non-fatal stroke, resuscitated cardiac arrest or cardiovascular death) for the entire study period was investigated using Cox proportional hazards models. The population was divided into four groups based on total bilirubin levels (normal range 5-25 µmol/L). Time-dependent Cox analyses were also performed to adjust for weight loss over time. Initial analyses adjusted for sex, age and treatment allocation showed significantly reduced hazard ratios of 0.80 (95% confidence interval 0.68-0.94), 0.73 (0.62-0.86) and 0.77 (0.65-0.91), for the three higher total bilirubin groups: >8 and ≤10 µmol/L, >10 and ≤13 µmol/L and >13 µmol/L (5-95 interpercentile range for total bilirubin at screening; 6-19 µmol/L), compared to the lowest total bilirubin group ≤8 µmol/L. When adjusting for classical cardiovascular risk factors, estimates increased towards unity. Additional adjustment for indicators of liver function did not alter the results. A time-dependent Cox model, adjusted for weight loss, demonstrated a similar trend. CONCLUSION: Bilirubin was not a risk-factor independent from other traditional cardiovascular risk-factors in our population.

A within-trial cost-effectiveness analysis of primary care referral to a commercial provider for weight loss treatment, relative to standard care--an international randomised controlled trial.

BACKGROUND: Due to the high prevalence of overweight and obesity there is a need to identify cost-effective approaches for weight loss in primary care and community settings. OBJECTIVE: We evaluated the cost effectiveness of two weight loss programmes of 1-year duration, either standard care (SC) as defined by national guidelines, or a commercial provider (Weight Watchers) (CP). DESIGN: This analysis was based on a randomised controlled trial of 772 adults (87% female; age 47.4±12.9 years; body mass index 31.4±2.6 kg m(-2)) recruited by health professionals in primary care in Australia, United Kingdom and Germany. Both a health sector and societal perspective were adopted to calculate the cost per kilogram of weight loss and the ICER, expressed as the cost per quality adjusted life year (QALY). RESULTS: The cost per kilogram of weight loss was USD122, 90 and 180 for the CP in Australia, the United Kingdom and Germany, respectively. For SC the cost was USD138, 151 and 133, respectively. From a health-sector perspective, the ICER for the CP relative to SC was USD18 266, 12 100 and 40 933 for Australia, the United Kingdom and Germany, respectively. Corresponding societal ICER figures were USD31,663, 24,996 and 51,571. CONCLUSION: The CP was a cost-effective approach from a health funder and societal perspective. Despite participants in the CP group attending two to three times more meetings than the SC group, the CP was still cost effective even including these added patient travel costs. This study indicates that it is cost effective for general practitioners (GPs) to refer overweight and obese patients to a CP, which may be better value than expending public funds on GP visits to manage this problem.

Comparability and utility of body composition measurement vs. anthropometric measurement for assessing obesity related health risks in Korean men.

BACKGROUND: Obesity is commonly assessed by body mass index (BMI) of which limitations come from an inability to distinguish body fat mass from lean mass. Several anthropometric measurements, including BMI, waist circumference, waist-to-height ratio and waist-to-hip ratio have been used to predict metabolic syndrome. The purpose of this study was to evaluate the utility of FMI or BF% combined with previous known anthropometric indices to assess the risk of metabolic syndrome in clinical practice. METHODS: In 5534 men visiting a hospital for health check-ups, blood tests, anthropometric measurements and body composition analysis using BIA were performed. Logistic regression analysis was performed to compare the odds ratios for metabolic syndrome and each component of metabolic syndrome among BMI, waist-to-height ratio, waist-to-hip ratio, FMI and BF%. The area under the curve (AUC) of the receiver operating characteristic curve (ROC) for metabolic syndrome was compared between several measurements. The net reclassification improvement with integrated discrimination improvement was used for assessing value of body composition measurement. RESULTS: The adjusted odds ratios of metabolic syndrome was 1.80 (95% CI, 1.71-1.89) for FMI and 1.15 (95% CI, 1.13-1.17) for BF%. Odds ratio of each metabolic component was highest for FMI among several anthropometric and body composition measurements. AUCs using the ROC curve for metabolic syndrome was highest for waist-to-height ratio, 0.823 (95% CI, 0.808-0.837) by National Cholesterol Education Program criteria. FMI caused a mild increase in integrated discrimination improvement when combined with waist-to-height ratio. CONCLUSIONS: Waist-to-height ratio seems to be the best screening tool for evaluating metabolic syndrome in Korean men, and adding FMI could result in a modest increase in integrated discrimination improvement.

A single blinded, phase IV, adaptive randomised control trial to evaluate the safety of coadministration of seasonal influenza and COVID-19 vaccines (The FluVID study).

OBJECTIVES: We evaluated the frequency of moderate and severe adverse events following coadministration of seasonal influenza vaccine (SIV) versus placebo with COVID-19 vaccines among adults to support practice guidelines. METHODS: FluVID is a participant-blinded, phase IV, randomised control trial. On the same day as the participant's scheduled COVID-19 vaccine, participants were randomised to receive SIV or saline placebo; those assigned placebo at visit one then received SIV a week later, and vice versa. Self-reported adverse events were collected daily for seven days following each visit. The primary endpoint was any solicited adverse event of at least moderate severity occurring up to seven days following receipt of SIV or placebo. This was modelled using a Bayesian logistic regression model. Analyses were performed by COVID-19 vaccine type and dose number. RESULTS: Overall, 248 participants were enrolled; of these, 195 had received BNT162b2 and 53 had received mRNA1273 COVID-19 vaccines according to national guidelines. After randomisation, 119 were assigned to receive SIV and 129 were assigned to receive placebo at visit one. Adverse events were most frequently reported as mild (grade 1) in nature. Among 142 BNT162b2 booster dose one and 43 BNT162b2 booster dose two recipients, the posterior median risk difference for moderate/severe adverse events following SIV versus placebo was 13% (95% credible interval [CrI] -0.03 to 0.27) and 13% (95%CrI -0.37 to 0.12), respectively. Among 18 mRNA1273 booster dose one and 35 mRNA1273 booster dose two recipients, the posterior median risk difference of moderate/severe adverse events following influenza vaccine versus placebo was 6% (95%CrI -0.29 to 0.41) and -4% (95%CrI -0.30 to 0.23), respectively. CONCLUSION: Adverse events following SIV and COVID-19 co-administration were generally mild and occurred with similar frequency to events following COVID-19 vaccine alone. We found no evidence to justify routine separation of SIV and COVID-19 vaccine doses. CLINICAL TRIAL REGISTRATION: ACTRN12621001063808.

Relationship between HbA1c levels and risk of cardiovascular adverse outcomes and all-cause mortality in overweight and obese cardiovascular high-risk women and men with type 2 diabetes.

AIMS/HYPOTHESIS: The optimal HbA(1c) concentration for prevention of macrovascular complications and deaths in obese cardiovascular high-risk patients with type 2 diabetes remains to be established and was therefore studied in this post hoc analysis of the Sibutramine Cardiovascular OUTcomes (SCOUT) trial, which enrolled overweight and obese patients with type 2 diabetes and/or cardiovascular disease. METHODS: HRs for meeting the primary endpoint (nonfatal myocardial infarction, nonfatal stroke, resuscitated cardiac arrest or cardiovascular death) and all-cause mortality were analysed using Cox regression models. RESULTS: Of 8,252 patients with type 2 diabetes included in SCOUT, 7,479 had measurements of HbA(1c) available at baseline (i.e. study randomisation). Median age was 62 years (range 51-86 years), median BMI was 34.0 kg/m(2) (24.8-65.1 kg/m(2)) and 44% were women. The median HbA(1c) concentration was 7.2% (3.8-15.9%) (55 mmol/l [18-150 mmol/l]) and median diabetes duration was 7 years (0-57 years). For each 1 percentage point HbA(1c) increase, the adjusted HR for the primary endpoint was 1.17 (95% CI 1.11, 1.23); no differential sex effect was observed (p = 0.12 for interaction). In contrast, the risk of all-cause mortality was found to be greater in women than in men: HR 1.22 (1.10, 1.34) vs 1.12 (1.04, 1.20) for each 1 percentage point HbA(1c) increase (p = 0.02 for interaction). There was no evidence of increased risk associated with HbA(1c) ≤ 6.4% (≤ 46 mmol/l). Glucose-lowering treatment regimens, diabetes duration or a history of cardiovascular disease did not modify the associations. CONCLUSIONS/INTERPRETATION: In overweight, cardiovascular high-risk patients with type 2 diabetes, increasing HbA(1c) concentrations were associated with increasing risks of cardiovascular adverse outcomes and all-cause mortality.

Weight loss in obese people has structure-modifying effects on medial but not on lateral knee articular cartilage.

BACKGROUND: Obesity is an important risk factor for knee osteoarthritis (OA), Weight loss can reduce the symptoms of knee OA. No prospective studies assessing the impact of weight loss on knee cartilage structure and composition have been performed. OBJECTIVES: To assess the impact of weight loss on knee cartilage thickness and composition. METHODS: 111 obese adults were recruited from either laparoscopic adjustable gastric banding or exercise and diet weight loss programmes from two tertiary centres. MRI was performed at baseline and 12-month follow-up to assess cartilage thickness. 78 eligible subjects also underwent delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), an estimate of proteoglycan content. The associations between cartilage outcomes (cartilage thickness and dGEMRIC index) and weight loss were adjusted for age, gender, body mass index (BMI) and presence of clinical knee OA. RESULTS: Mean age was 51.7 ± 11.8 years and mean BMI was 36.6 ± 5.8 kg/m(2); 32% had clinical knee OA. Mean weight loss was 9.3 ± 11.9%. Percentage weight loss was negatively associated with cartilage thickness loss in the medial femoral compartment in multiple regression analysis (ß=0.006, r(2)=0.19, p=0.029). This association was not detected in the lateral compartment (r(2)=0.12, p=0.745). Percentage weight loss was associated with an increase in medial dGEMRIC in multiple regression analysis (ß=3.9, r(2)=0.26; p=0.008) but not the lateral compartment (r(2)=0.14, p=0.34). For every 10% weight loss there was a gain in the medial dGEMRIC index of 39 ms (r(2)=0.28; p=0.014). The lowest weight loss cut-off associated with reduced medial femoral cartilage thickness loss and improved medial dGEMRIC index was 7%. CONCLUSIONS: Weight loss is associated with improvements in the quality (increased proteoglycan content) and quantity (reduced cartilage thickness losses) of medial articular cartilage. This was not observed in the lateral compartment. This could ultimately lead to a reduced need for total joint replacements and is thus a finding with important public health implications.

Maintained intentional weight loss reduces cardiovascular outcomes: results from the Sibutramine Cardiovascular OUTcomes (SCOUT) trial.

AIM: The Sibutramine Cardiovascular OUTcomes trial showed that sibutramine produced greater mean weight loss than placebo but increased cardiovascular morbidity but not mortality. The relationship between 12-month weight loss and subsequent cardiovascular outcomes is explored. METHODS: Overweight/obese subjects (N = 10 744), ≥55 years with cardiovascular disease and/or type 2 diabetes mellitus, received sibutramine plus weight management during a 6-week Lead-in Period before randomization to continue sibutramine (N = 4906) or to receive placebo (N = 4898). The primary endpoint was the time from randomization to first occurrence of a primary outcome event (non-fatal myocardial infarction, non-fatal stroke, resuscitated cardiac arrest or cardiovascular death). RESULTS: For the total population, mean weight change during Lead-in Period (sibutramine) was -2.54 kg. Post-randomization, mean total weight change to Month 12 was -4.18 kg (sibutramine) or -1.87 kg (placebo). Degree of weight loss during Lead-in Period or through Month 12 was associated with a progressive reduction in risk for the total population in primary outcome events and cardiovascular mortality over the 5-year assessment. Although more events occurred in the randomized sibutramine group, on an average, a modest weight loss of approximately 3 kg achieved in the Lead-in Period appeared to offset this increased event rate. Moderate weight loss (3-10 kg) reduced cardiovascular deaths in those with severe, moderate or mild cardiovascular disease. CONCLUSIONS: Modest weight loss over short-term (6 weeks) and longer-term (6-12 months) periods is associated with reduction in subsequent cardiovascular mortality for the following 4-5 years even in those with pre-existing cardiovascular disease. While the sibutramine group experienced more primary outcome events than the placebo group, greater weight loss reduced overall risk of these occurring in both groups.

Coordinated improvement in glucose tolerance, liver steatosis and obesity-associated inflammation by cannabinoid 1 receptor antagonism in fat Aussie mice.

OBJECTIVE: Fat Aussie mice (foz/foz) are morbidly obese, glucose intolerant and have liver steatosis that develops into steatohepatitis on a high-fat diet. The cannabinoid 1 receptor (CB1) antagonist SR141716 has been shown to improve obesity-associated metabolic complications in humans and rodent models. The aim of this study was to assess the effect of SR141716 in foz/foz mice. DESIGN: Male wildtype (WT) and foz/foz mice were fed a chow or high-fat diet (45% saturated fat). Vehicle or SR141716 (10 mg kg(-1) per day) was administered in jelly once daily for 4 weeks from 4 months of age. RESULTS: Foz/foz mice were obese but had less epididymal adipose tissue mass than fat-fed WT mice despite being significantly heavier. Liver weight was increased by twofold in foz/foz compared with WT mice and showed significant steatogenesis associated with impaired liver function. Foz/foz and fat-fed WT mice were glucose intolerant as determined by oral glucose tolerance test. In chow-fed foz/foz mice, SR141716 reduced body weight, liver weight, reversed hepatosteatosis and glucose intolerance. Subcutaneous white adipose tissue gene expression of the macrophage-specific marker Cd68 reflected the improvements in the metabolic status by SR141716 in these mice. CONCLUSION: The results are consistent with the hypothesis that foz/foz mice have defective lipid metabolism, are unable to adequately store fat in adipose tissue but instead sequester fat ectopically in other metabolic tissues (liver) leading to insulin resistance and hepatic steatosis associated with inflammation. Our findings suggest that SR141716 can improve liver lipid metabolism in foz/foz mice in line with improved insulin sensitivity and adipose tissue inflammation.

Weight and blood pressure response to weight management and sibutramine in diabetic and non-diabetic high-risk patients: an analysis from the 6-week lead-in period of the sibutramine cardiovascular outcomes (SCOUT) trial.

OBJECTIVE: To assess treatment responses to sibutramine and weight management in diabetic patients during the lead-in period of the Sibutramine Cardiovascular OUTcomes (SCOUT) trial. METHODS: SCOUT is an ongoing, prospective, randomized, double-blind, placebo-controlled outcome trial in cardiovascular high-risk overweight/obese patients. A total of 10 742 patients received single-blind sibutramine and individualized weight management during the 6-week lead-in period; 84% had a history of type 2 diabetes mellitus and additional co-morbidities. Post-hoc analyses assessed anthropomorphic and vital sign responses between patients with and without diabetes. RESULTS: Concomitant antidiabetic medication use was reported by 86% of the diabetic patients (approximately 30% required insulin-alone or in combination). Body weight and waist circumference decreased in diabetic patients: median 2.1 kg; 2.0 cm (both men and women); for those on insulin: 1.9 kg; 1.5/2.0 cm (men/women); without insulin: 2.3 kg; 2.0 cm (both men and women); blood pressure (BP) was also reduced (median systolic/diastolic 3.5/1.0 mmHg) with larger reductions in diabetic patients who were hypertensive and/or lost the most weight (>5%). In diabetic patients who entered with BP at target (<130/<85 mmHg) but did not lose weight (N = 245), increases of 3.5/2.0 mmHg were observed. Non-diabetic patients had greater weight losses (2.5 kg) but smaller reductions in BP (systolic/diastolic -2.5/-0.5 mmHg). Pulse rate increases were less in diabetic vs. non-diabetic patients (1.5 vs. 2.0 bpm). CONCLUSION: In these high-risk diabetic patients, sibutramine and lifestyle modifications for 6 weeks resulted in small, but clinically relevant, median reductions in body weight, waist circumference and BP. A small median increase in pulse rate was recorded.

Overview of endocrinopathies associated with ß-thalassaemia major.

BACKGROUND: Thalassaemia major is a common and serious medical problem worldwide that is associated with a range of complications, including effects on multiple endocrine pathways. Minimizing or preventing comorbidities is important for these individuals who need life-long multidisciplinary care and treatment. However, there are limited overviews of the endocrine complications associated with this illness, nor any consensus regarding management guidelines. METHOD: A retrospective cohort analysis of ß-thalassaemia patients attending an ambulatory transfusion clinic at Royal Prince Alfred Hospital was conducted from June 2008. RESULTS: All of our subjects (n=29) had at least one endocrinopathy present with 16 patients (55%) having three or more (≥3) endocrinopathies. Hypogonadism was the most prevalent followed by osteoporosis and growth failure (less than 3rd centile) with a frequency of 16/29 (55%), 14/29 (48%) and 10/29 (35%) patients respectively. Those with more endocrinopathies (≥3) had a longer duration of transfusion therapy when compared with those with fewer endocrinopathies. CONCLUSION: A summary of our clinical guidelines, which have been used to monitor and manage these complications, is presented along with a discussion on the results and pathophysiology of the associated endocrinopathies.

The use of motivational enhancement strategies for the maintenance of weight loss among obese individuals: a preliminary investigation.

AIM: To investigate the efficacy of motivational enhancement strategies integrated within a standard lifestyle modification program for the maintenance of weight loss and improved psychosocial functioning of obese adults. METHODS: Twenty-two obese adults completed 20 sessions of a motivationally informed cognitive behavioural treatment for weight loss and maintenance. Treatment outcome measures included anthropometrics, obesity-specific quality of life, impulsive eating tendencies, body dissatisfaction, mood disturbance and maladaptive cognitions. RESULTS: At post-treatment, there was a significant decrease in body weight (123.04 +/- 22.06 vs. 116.84 +/- 23.53, p < 0.001) with no significant change by the 12-month follow-up. Patients also reported significant improvements in obesity-related quality of life, impulsive eating tendencies, body dissatisfaction and maladaptive cognitions at post-treatment that were maintained at the 1-year follow-up. CONCLUSIONS: The implementation of motivational enhancement strategies within a cognitive behavioural program results in sustained weight loss that compares favourably to previous lifestyle modification programs.

Blood pressure changes associated with sibutramine and weight management - an analysis from the 6-week lead-in period of the sibutramine cardiovascular outcomes trial (SCOUT).

OBJECTIVE: To explore vital sign changes among patient subgroups during the 6-week lead-in period of the sibutramine cardiovascular outcomes (SCOUT) trial. METHODS: SCOUT is an ongoing, double-blind, randomized, placebo-controlled outcome trial in overweight/obese patients at high risk of a cardiovascular event. During the 6-week lead-in period, 10,742 patients received sibutramine and weight management. Vital sign changes were assessed post hoc by initial blood pressure (mmHg) categorized as normal (<130/<85), high-normal (130 to <140/85 to <90) or hypertensive (>or=140/>or=90); weight change categories (weight gain/no weight change, >0 to 2.5% weight loss, >2.5 to 5% weight loss and >5% weight loss) and current antihypertensive medication class use (none, one, or two or more). To assess the impact of sibutramine on blood pressure and pulse rate, only patients (N = 10,025) who reported no change in the class of antihypertensive medication used and who did not report an increase in antihypertensive medication use were analysed. RESULTS: At entry, approximately 50% of patients were hypertensive and 26% were high-normal. In hypertensive patients, blood pressure changes (mmHg) decreased by median [5th, 95th percentile] of -6.5 systolic [-27.0, 8.0] and -2.0 diastolic [-15.0, 8.0] (p < 0.001). Hypertensive patients with no weight loss or with weight gain had median decreases of -3.5 systolic [-26.0, 10.0] and -1.5 diastolic [-16.0, 9.0] (p < 0.001). Normotensive patients had median increases of 1.5 systolic [-15.0, 19.5] and 1.0 diastolic [-10.5, 13.0] (p < 0.001) attenuated with increasing weight loss. Approximately 43% of patients initially categorized as hypertensive had a lower blood pressure category at end-point. Concomitant antihypertensive medication classes did not affect blood pressure reductions. Pulse rates were uniformly elevated (median 1-4 bpm, p < 0.001) across blood pressure and weight change categories. CONCLUSIONS: In hypertensive patients (>or=140/>or=90), blood pressure decreases were observed during 6-week treatment with sibutramine even when body weight was unchanged. In patients with normal blood pressure (<130/<85), weight loss of >5% induced decreases in systolic blood pressure; otherwise, small increases were observed. Small pulse rate increases were observed regardless of blood pressure or weight change status.

The impact of obesity on the musculoskeletal system.

Obesity is associated with a range of disabling musculoskeletal conditions in adults. As the prevalence of obesity increases, the societal burden of these chronic musculoskeletal conditions, in terms of disability, health-related quality of life, and health-care costs, also increases. Research exploring the nature and strength of the associations between obesity and musculoskeletal conditions is accumulating, providing a better understanding of underlying mechanisms. Weight reduction is important in ameliorating some of the manifestations of musculoskeletal disease and improving function.

The effects of obesity and non-pharmacological weight loss on vascular and ventricular function and structure.

AIMS: The mechanisms by which obesity confers increased cardiovascular risk and the effects of moderate weight loss on cardiovascular health are incompletely understood. We sought to characterize the preclinical changes in cardiac and vascular health that accompany obesity and the influence of lifestyle modification on these parameters. METHODS: Preclinical markers of vasculopathy in resistance vessels and conduit arteries and left ventricular structure and function were assessed in 39 obese subjects (BMI > 30 kg/m(2)) and 11 healthy weight controls. The influence of serum on cellular adhesion molecule (CAM) expression on human endothelial cells was studied ex vivo in a subgroup of 13 obese and nine healthy weight subjects. These analyses were repeated in all 17 of the obese subjects who complied with 4-9 months of lifestyle modification treatment (six with weight loss >5% and 11 with weight loss <5%). RESULTS: Compared with healthy weight controls, obese subjects had decreased peak hyperaemic forearm blood flow (p = 0.015), increased carotid intima-media thickness (p = 0.009), increased left ventricular wall thickness and volume and evidence of systolic and diastolic dysfunction as assessed using tissue Doppler imaging (S', p = 0.09; E'/A', p = 0.02), and serum from obese subjects increased the intercellular CAM-1 expression on human endothelial cells (p = 0.009). However, arterial endothelial function assessed by flow-mediated dilatation was not altered (p = 0.99). Lifestyle modification treatment resulted in potentially beneficial changes in fibrinogen (p = 0.003), HDL cholesterol (p = 0.05) and soluble vascular CAM-1 (p = 0.06). In subjects with weight loss greater than 5% of body weight, there was also a decrease in low-level inflammation (high-sensitivity C-reactive protein, p = 0.05), lipid peroxidation (thiobarbituric acid-reactive substances, p = 0.05) and triglycerides (p = 0.07). CONCLUSIONS: Obesity is associated with widespread alterations in cardiac and vascular structure and function. Moderate short-term weight loss by lifestyle modification results in some beneficial changes in serum profile; however, these are not accompanied by significant alterations to either cardiac or vascular structure and function.

PROCEED: Prospective Obesity Cohort of Economic Evaluation and Determinants: baseline health and healthcare utilization of the US sample.

AIM: To summarize baseline characteristics, health conditions, resource utilization and resource cost for the US population for the 90-day period preceding enrolment, stratified by body mass index (BMI) and the presence of abdominal obesity (AO). METHODS: PROCEED (Prospective Obesity Cohort of Economic Evaluation and Determinants) is a multinational, prospective cohort of control (BMI 20-24.0 kg/m(2)), overweight (BMI 25-29.9 kg/m(2)) and obese (BMI >or= 30 kg/m(2)) subjects with AO and without AO [non-abdominal obesity (NAO)], defined by waist circumference (WC) >102 and 88 cm for males and females, respectively. Subjects were recruited from an Internet consumer panel. Outcomes were self-reported online. Self-reported anthropometric data were validated. Prevalence of conditions and utilization is presented by BMI class and AO within BMI class. Differences in prevalence and means were evaluated. RESULTS: A total of 1067 overweight [n = 474 (NAO: n = 254 and AO: n = 220)] and obese [n = 493 (NAO: n = 39 and AO: n = 454)] subjects and 100 controls were recruited. Self-reported weight (r = 0.92) and WC (r = 0.87) were correlated with measured assessments. Prevalence of symptoms was significantly higher in groups with higher BMI, as were hypertension (p < 0.0001), diabetes (p < 0.0001) and sleep apnoea (p < 0.0001). Metabolic risk factors increased with the BMI class. Among the overweight class, subjects with AO had significantly more reported respiratory, heart, nervous, skin and reproductive system symptoms. Overweight subjects with AO reported a significantly higher prevalence of diabetes (13%) compared with overweight subjects with NAO (7%, p = 0.04). Mean healthcare cost was significantly higher in the higher BMI classes [control ($456 +/- 937) vs. overweight ($1084 +/- 3531) and obese ($1186 +/- 2808) (p < 0.0001)]. CONCLUSION: An increasing gradient of symptoms, medical conditions, metabolic risk factors and healthcare utilization among those with a greater degree of obesity was observed. The independent effect of AO on health and healthcare utilization deserves further study with a larger sample size.