Priya Sumithran

The defence of body weight: a physiological basis for weight regain after weight loss.

Although weight loss can usually be achieved by restricting food intake, the majority of dieters regain weight over the long-term. In the hypothalamus, hormonal signals from the gastrointestinal tract, adipose tissue and other peripheral sites are integrated to influence appetite and energy expenditure. Diet-induced weight loss is accompanied by several physiological changes which encourage weight regain, including alterations in energy expenditure, substrate metabolism and hormone pathways involved in appetite regulation, many of which persist beyond the initial weight loss period. Safe effective long-term strategies to overcome these physiological changes are needed to help facilitate maintenance of weight loss. The present review, which focuses on data from human studies, begins with an outline of body weight regulation to provide the context for the subsequent discussion of short- and long-term physiological changes which accompany diet-induced weight loss.

The effect of rate of weight loss on long-term weight management: a randomised controlled trial

BACKGROUND Guidelines recommend gradual weight loss for the treatment of obesity, indicative of a widely held opinion that weight lost rapidly is more quickly regained. We aimed to investigate the effect of the rate of weight loss on the rate of regain in obese people. METHODS For this two phase, randomised, non-masked, dietary intervention trial in a Melbourne metropolitan hospital, we enrolled 204 participants (51 men and 153 women) aged 18–70 years with a BMI between 30 and 45 kg/m2. During phase 1, we randomly assigned (1:1) participants with a block design (block sizes of 2, 4, and 6) to account for sex, age, and BMI, to either a 12-week rapid weight loss or a 36-week gradual programme, both aimed at 15% weight loss. We placed participants who lost 12·5% or more weight during phase 1 on a weight maintenance diet for 144 weeks (phase 2). The primary outcome was mean weight loss maintained at week 144 of phase 2. We investigated the primary outcome by both completers only and intention-to-treat analyses. This study is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12611000190909. FINDINGS 200 participants were randomly assigned to the gradual weight loss (n=103) or rapid weight loss (n=97) programme between Aug 8, 2008, and March 9, 2010. After phase 1, 51 (50%) participants in the gradual weight loss group and 76 (81%) in the rapid weight loss group achieved 12·5% or more weight loss in the allocated time and started phase 2. At the end of phase 2, both gradual weight loss and rapid weight loss participants who completed the study (n=43 in gradual weight loss and n=61 in rapid weight loss) had regained most of their lost weight (gradual weight loss 71·2% regain, 95% CI 58·1–84·3 vs rapid weight loss 70·5%, 57·8–83·2). Intention-to-treat analysis showed similar results (gradual weight loss 76·3% regain, 95% CI 65·2–87·4 vs rapid weight loss 76·3%, 65·8–86·8). In phase 1, one participant in the rapid weight loss group developed cholecystitis, requiring cholecystectomy. In phase 2, two participants in the rapid weight loss group developed cancer. INTERPRETATION The rate of weight loss does not affect the proportion of weight regained within 144 weeks. These findings are not consistent with present dietary guidelines which recommend gradual over rapid weight loss, based on the belief that rapid weight loss is more quickly regained. FUNDING The Australian National Health and Medical Research Council and the Sir Edward Dunlop Medical Research Foundation.

Ketosis and appetite-mediating nutrients and hormones after weight loss

Background/Objectives:Diet-induced weight loss is accompanied by compensatory changes, which increase appetite and encourage weight regain. There is some evidence that ketogenic diets suppress appetite. The objective is to examine the effect of ketosis on a number of circulating factors involved in appetite regulation, following diet-induced weight loss.Subjects/Methods:Of 50 non-diabetic overweight or obese subjects who began the study, 39 completed an 8-week ketogenic very-low-energy diet (VLED), followed by 2 weeks of reintroduction of foods. Following weight loss, circulating concentrations of glucose, insulin, non-esterified fatty acids (NEFA), β-hydroxybutyrate (BHB), leptin, gastrointestinal hormones and subjective ratings of appetite were compared when subjects were ketotic, and after refeeding.Results:During the ketogenic VLED, subjects lost 13% of initial weight and fasting BHB increased from (mean±s.e.m.) 0.07±0.00 to 0.48±0.07 mmol/l (P<0.001). BHB fell to 0.19±0.03 mmol/l after 2 weeks of refeeding (P<0.001 compared with week 8). When participants were ketotic, the weight loss induced increase in ghrelin was suppressed. Glucose and NEFA were higher, and amylin, leptin and subjective ratings of appetite were lower at week 8 than after refeeding.Conclusions:The circulating concentrations of several hormones and nutrients which influence appetite were altered after weight loss induced by a ketogenic diet, compared with after refeeding. The increase in circulating ghrelin and subjective appetite which accompany dietary weight reduction were mitigated when weight-reduced participants were ketotic.

Review of 3-year outcomes of a very-low-energy diet-based outpatient obesity treatment programme.

Obesity is a complex disorder that requires a multidisciplinary treatment approach. This review evaluated 3‐year outcomes of a very‐low‐energy diet (VLED)‐based programme at a tertiary hospital multidisciplinary weight management clinic. Medical records of all patients who agreed to undertake the VLED programme and who did not undergo bariatric surgery during the 3‐year follow‐up period were examined. Baseline data collection included demographic and anthropometric characteristics, childhood onset of obesity and co‐existing medical conditions. Weight was modelled using a linear mixed effects analysis. Logistic regression analyses were used to model the probability of continuing to attend the clinic and to identify pre‐treatment factors associated with longer duration of attendance. Data from 1109 patients were included. A total of 231 patients (19.2%) were still attending the clinic 3 years after their initial appointment. Mean weight loss among patients who attended the clinic for 3 years was 6.4 kg (3.5%, 95% confidence interval [CI] 2.8, 4.2%). People who were prescribed pharmacotherapy maintained greater weight loss at 3 years (7.7% vs. 2.3% without pharmacotherapy, 95% CI for difference 3.9, 7.0%). People who had an onset of obesity in childhood, who had co‐existing hypertension or coronary artery disease, and who did not currently smoke were more likely to continue to attend the clinic for up to 3 years. In summary, in an outpatient weight management clinic, patients who undertook a VLED‐based programme and continued in follow‐up achieved a clinically significant weight loss at 3 years, particularly if pharmacotherapy was used for weight loss maintenance.

Combination phentermine and topiramate for weight maintenance: the first Australian experience.

Objective: To investigate the safety, tolerability and efficacy of combination phentermine and topiramate therapy for maintenance of weight loss.

Using Automated HbA1c Testing to Detect Diabetes Mellitus in Orthopedic Inpatients and Its Effect on Outcomes

Aims The prevalence of diabetes is rising, and people with diabetes have higher rates of musculoskeletal-related comorbidities. HbA1c testing is a superior option for diabetes diagnosis in the inpatient setting. This study aimed to (i) demonstrate the feasibility of routine HbA1c testing to detect the presence of diabetes mellitus, (ii) to determine the prevalence of diabetes in orthopedic inpatients and (iii) to assess the association between diabetes and hospital outcomes and post-operative complications in orthopedic inpatients. Methods All patients aged ≥54 years admitted to Austin Health between July 2013 and January 2014 had routine automated HbA1c measurements using automated clinical information systems (CERNER). Patients with HbA1c ≥6.5% were diagnosed with diabetes. Baseline demographic and clinical data were obtained from hospital records. Results Of the 416 orthopedic inpatients included in this study, 22% (n = 93) were known to have diabetes, 4% (n = 15) had previously unrecognized diabetes and 74% (n = 308) did not have diabetes. Patients with diabetes had significantly higher Charlson comorbidity scores compared to patients without diabetes (median, IQR; 1 [0,2] vs 0 [0,0], p<0.001). After adjusting for age, gender, comorbidity score and estimated glomerular filtration rate, no significant differences in the length of stay (IRR = 0.92; 95%CI: 0.79–1.07; p = 0.280), rates of intensive care unit admission (OR = 1.04; 95%CI: 0.42–2.60, p = 0.934), 6-month mortality (OR = 0.52; 95%CI: 0.17–1.60, p = 0.252), 6-month hospital readmission (OR = 0.93; 95%CI: 0.46–1.87; p = 0.828) or any post-operative complications (OR = 0.98; 95%CI: 0.53–1.80; p = 0.944) were observed between patients with and without diabetes. Conclusions Routine HbA1c measurement using CERNER allows for rapid identification of inpatients admitted with diabetes. More than one in four patients admitted to a tertiary hospital orthopedic ward have diabetes. No statistically significant differences in the rates of hospital outcomes and post-operative complications were identified between patients with and without diabetes.

Maintaining Weight Loss: an Ongoing Challenge

For most people who have intentionally lost a substantial amount of weight, maintaining that weight loss takes a lot of effort. Despite their intentions to the contrary, the majority of people will eventually regain most, if not all, of the weight that they managed to lose [1]. Why is this so? A recent paper from Fothergill and colleagues [2], reporting long-term data from participants in the televised BBiggest Loser^ weight loss competition, adds to the growing evidence that weight reduction brings about biological adaptations which favour weight regain. This study examined body composition, energy expenditure and biochemical parameters in 14 of the 16 people with severe obesity who had taken part in the Biggest Loser competition 6 years earlier. While housed together, contestants performed 90min of supervised vigorous circuit and/or aerobic training 6 days per week, and additional exercise of up to 3 h per day was encouraged. They were also advised to restrict their dietary energy intake to at least 70% of estimated baseline requirements. Every 7–10 days, one participant was sent home, and all remaining contestants returned home after week 13, to continue their weight loss program unsupervised until the end of the competition at week 30 [3]. At the start of the contest, mean (±SD) weight of the 14 participants was 148.9 ± 40.5 kg (BMI 49.5 ± 10.1 kg/m). Over the 30-week competition, mean weight loss was 58.3 ± 24.9 kg, and 6 years later, a mean of 41.0 ± 31.3 kg had been regained. Measured resting metabolic rate (RMR) fell from 2607 ± 649 kcal/day at baseline to 1996 ± 358 kcal/day by week 30, and despite considerable weight regain 6 years later, the reduction in RMR was sustained (1903 ± 466 kcal/day). The most notable finding of this study was that measured RMR was 275 kcal/day lower than predicted for changes in body composition and age at week 30, and this gap (Bmetabolic adaptation^) increased to 499 kcal/day at 6 years. The degree of metabolic adaptation at 6 years (but not 30 weeks) correlated with percent weight regain [2]. While it could be argued that the extreme intensity of the exercise and diet regimen undertaken by the Biggest Loser contestants makes these findings difficult to extrapolate to less rigorous weight loss interventions, the results are in accordance with other studies in which metabolic adaptation has been documented after more moderate weight loss. A 10 % reduction in body weight due to dietary restriction is accompanied by a reduction in total energy expenditure (TEE) to a level 15 % below that which can be accounted for by alterations in body mass and composition in both lean and obese people [4], and this disproportionate decline in TEE persists for at least 1 year of maintenance of the reduced body weight [5]. In a recent reanalysis of data from their previous inpatient metabolic studies [6], Rosenbaum and Leibel concluded that the decline in TEE with 10 % weight loss reflects roughly equivalent reductions in resting and non-resting energy expenditure, whereas the continuing fall in TEE during a further 10 % (i.e., total 20 %) weight loss is contributed to primarily by changes in non-resting energy expenditure. Several studies have indicated that compensatory changes as a result of diet-induced weight reduction occur not only in energy expenditure but also in circulating concentrations of a * Priya Sumithran priyas@unimelb.edu.au

Routine use of HbA1c amongst inpatients hospitalised with decompensated heart failure and the association of dysglycaemia with outcomes

Diabetes is an independent risk factor for development of heart failure and has been associated with poor outcomes in these patients. The prevalence of diabetes continues to rise. Using routine HbA1c measurements on inpatients at a tertiary hospital, we aimed to investigate the prevalence of diabetes amongst patients hospitalised with decompensated heart failure and the association of dysglycaemia with hospital outcomes and mortality. 1191 heart failure admissions were identified and of these, 49% had diabetes (HbA1c ≥ 6.5%) and 34% had pre-diabetes (HbA1c 5.7–6.4%). Using a multivariable analysis adjusting for age, Charlson comorbidity score (excluding diabetes and age) and estimated glomerular filtration rate, diabetes was not associated with length of stay (LOS), Intensive Care Unit (ICU) admission or 28-day readmission. However, diabetes was associated with a lower risk of 6-month mortality. This finding was also supported using HbA1c as a continuous variable. The diabetes group were more likely to have diastolic dysfunction and to be on evidence-based cardiac medications. These observational data are hypothesis generating and possible explanations include that more diabetic patients were on medications that have proven mortality benefit or prevent cardiac remodelling, such as renin-angiotensin system antagonists, which may modulate the severity of heart failure and its consequences.

Clinical Obesity Services in Public Hospitals in Australia: a position statement based on expert consensus: Expert consensus on clinical obesity services

We aimed to describe the current state of specialist obesity services for adults with clinically severe obesity in public hospitals in Australia, and to analyse the gap in resources based on expert consensus. We conducted two surveys to collect information about current and required specialist obesity services and resources using open‐ended questionnaires. Organizational level data were sought from clinician expert representatives of specialist obesity services across Australia in 2017. Fifteen of 16 representatives of current services in New South Wales (n = 8), Queensland (n = 1), Victoria (n = 2), South Australia (n = 3), and the Australian Capital Territory (n = 1) provided data. The composition of services varied substantially between hospitals, and patient access to services and effective treatments were limited by strict entry criteria (e.g. body mass index 40 kg/m2 or higher with specific complication/s), prolonged wait times, geographical location (major cities only) and out‐of‐pocket costs. Of these services, 47% had a multidisciplinary team (MDT), 53% had an exercise physiologist/physiotherapist, 53% had a bariatric surgeon and 33% had pharmacotherapy resources. Key gaps included staffing components of the MDT (psychologist, exercise physiologist/physiotherapist) and access to publicly funded weight loss pharmacotherapy and bariatric surgery. There was consensus on the need for significant improvements in staff, physical infrastructure, access to services, education/training in obesity medicine and targeted research funding. Based on the small number of existing, often under‐resourced specialist obesity services that are located only in a few major cities, the vast majority of Australians with clinically severe obesity cannot access the specialist evidence based treatments needed.

Combining biological and psychosocial baseline variables did not improve prediction of outcome of a very-low-energy diet in a clinic referral population: Combining data did not improve outcome prediction

Consistent, strong predictors of obesity treatment outcomes have not been identified. It has been suggested that broadening the range of predictor variables examined may be valuable. We explored methods to predict outcomes of a very‐low‐energy diet (VLED)‐based programme in a clinically comparable setting, using a wide array of pre‐intervention biological and psychosocial participant data. A total of 61 women and 39 men (mean ± standard deviation [SD] body mass index: 39.8 ± 7.3 kg/m2) underwent an 8‐week VLED and 12‐month follow‐up. At baseline, participants underwent a blood test and assessment of psychological, social and behavioural factors previously associated with treatment outcomes. Logistic regression, linear discriminant analysis, decision trees and random forests were used to model outcomes from baseline variables. Of the 100 participants, 88 completed the VLED and 42 attended the Week 60 visit. Overall prediction rates for weight loss of ≥10% at weeks 8 and 60, and attrition at Week 60, using combined data were between 77.8 and 87.6% for logistic regression, and lower for other methods. When logistic regression analyses included only baseline demographic and anthropometric variables, prediction rates were 76.2–86.1%. In this population, considering a wide range of biological and psychosocial data did not improve outcome prediction compared to simply‐obtained baseline characteristics.