Luke A. Prendergast

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.

One-year weight maintenance after significant weight loss in healthy overweight and obese subjects: does diet composition matter?

BACKGROUND For many people, maintenance of weight loss is elusive. Whereas high-protein (HP) diets have been found to be superior to high-carbohydrate (HC) diets for weight loss in the short term, their benefits long term are unclear, particularly for weight maintenance. Furthermore, the literature lacks consensus on the long-term effects of an HP diet on cardiovascular disease risk factors. OBJECTIVE The objective was to investigate whether macronutrient dietary composition plays a role in weight maintenance and in improvement of cardiovascular disease risk factors. DESIGN The study comprised 2 phases. Phase 1 featured a very-low-energy diet for 3 mo. In phase 2, the subjects were randomly assigned to an HP or an HC diet for 12 mo. The diets were isocaloric, tightly controlled, and individually prescribed for weight maintenance. The subjects were overweight or obese but otherwise healthy men and women. RESULTS The subjects lost an average of 16.5 kg during phase 1 and maintained a mean (+/-SEM) weight loss of 14.5 +/- 1.2 kg (P < 0.001) during phase 2; no significant differences between groups were observed. By the end of the study, reductions in systolic blood pressure were 14.3 +/- 2.4 mm Hg for the HP group and 7.7 +/- 2.2 mm Hg for the HC group (P < 0.045). Forty-seven percent of the 180 subjects who began the study completed both phases. CONCLUSIONS The results indicate that the protein or carbohydrate content of the diet has no effect on successful weight-loss maintenance. A general linear model analysis indicated that dietary treatment (HP or HC) was a significant factor in systolic blood pressure change and in favor of the HP diet. This trial was registered at www.clinicaltrials.gov as NCT 00625236.

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.

Moderate-intensity exercise reduces fatigue and improves mobility in cancer survivors: a systematic review and meta-regression

QUESTION Is there a dose-response effect of exercise on inflammation, fatigue and activity in cancer survivors? DESIGN Systematic review with meta-regression analysis of randomised trials. PARTICIPANTS Adults diagnosed with cancer, regardless of specific diagnosis or treatment. INTERVENTION Exercise interventions including aerobic and/or resistance as a key component. OUTCOME MEASURES The primary outcome measures were markers of inflammation (including C-reactive protein and interleukins) and various measures of fatigue. The secondary outcomes were: measures of activity, as defined by the World Health Organizations International Classification of Functioning, Disability and Health, including activities of daily living and measures of functional mobility (eg, 6-minute walk test, timed sit-to-stand and stair-climb tests). Risk of bias was evaluated using the PEDro scale, and overall quality of evidence was assessed using the Grades of Research, Assessment, Development and Evaluation (GRADE) approach. RESULTS Forty-two trials involving 3816 participants were included. There was very low-quality to moderate-quality evidence that exercise results in significant reductions in fatigue (SMD 0.32, 95% CI 0.13 to 0.52) and increased walking endurance (SMD 0.77, 95% CI 0.26 to 1.28). A significant negative association was found between aerobic exercise intensity and fatigue reduction. A peak effect was found for moderate-intensity aerobic exercise for improving walking endurance. No dose-response relationship was found between exercise and markers of inflammation or exercise duration and outcomes. Rates of adherence were typically high and few adverse events were reported. CONCLUSIONS Exercise is safe, reduces fatigue and increases endurance in cancer survivors. The results support the recommendation of prescribing moderate-intensity aerobic exercise to reduce fatigue and improve activity in people with cancer. REVIEW REGISTRATION PROSPERO CRD42015019164.

A note on sensitivity of principal component subspaces and the efficient detection of influential observations in high dimensions

In this paper we introduce an influence measure based on second order expansion of the RV and GCD measures for the comparison between unperturbed and perturbed eigenvectors of a symmetric matrix estimator. Example estimators are considered to highlight how this measure compliments recent influence analysis. Importantly, we also show how a sample based version of this measure can be used to accurately and efficiently detect influential observations in practice.

Less fat reduction per unit weight loss in type 2 diabetic compared with nondiabetic obese individuals completing a very-low-calorie diet program

The objective was to compare weight loss and change in body composition in obese subjects with and without type 2 diabetes mellitus during a very-low-calorie diet (VLCD) program. Seventy weight-matched subjects with diabetes or normal fasting glucose (controls) participated in a 24-week VLCD study. Primary end points were changes in anthropometry, body composition, and fasting plasma insulin and β-hydroxybutyrate concentrations. Fifty-one subjects (24 with diabetes) completed the study. No difference in weight loss between the 2 groups at 24 weeks was found by intention-to-treat analysis. Both groups completing the study per protocol had near-identical weight change during the program, with similar weight loss at 24 weeks (diabetes: 8.5 ± 1.3 kg vs control: 9.4 ± 1.2 kg, P = .64). Change in fat mass index correlated with change in body mass index (BMI) in both groups (diabetes: r = 0.878, control: r = 0.920, both P < .001); but change in fat mass index per unit change in BMI was less in the diabetic group compared with controls (0.574 vs 0.905 decrease, P = .003), which persisted after adjusting for age, sex, and baseline BMI (P = .008). Insulin concentrations remained higher and peak β-hydroxybutyrate concentrations were lower in the diabetic compared with the control group. While following a 24-week VLCD program, obese subjects with and without diabetes achieved comparable weight loss; but the decrease in adiposity per unit weight loss was attenuated in diabetic subjects. Hyperinsulinemia may have inhibited lipolysis in the diabetic group; however, further investigation into other factors is needed.

Severity of Autism is Related to Children's Language Processing

Problems in language processing have been associated with autism spectrum disorder (ASD), with some research attributing the problems to overall language skills rather than a diagnosis of ASD. Lexical access was assessed in a looking‐while‐listening task in three groups of 5‐ to 7‐year‐old children; two had high‐functioning ASD (HFA), an ASD severe (ASD‐S) group (n = 16) and an ASD moderate (ASD‐M) group (n = 21). The third group were typically developing (TD) (n = 48). Participants heard sentences of the form “Wheres the x?” and their eye movements to targets (e.g., train), phonological competitors (e.g., tree), and distractors were recorded. Proportions of looking time at target were analyzed within 200 ms intervals. Significant group differences were found between the ASD‐S and TD groups only, at time intervals 1000–1200 and 1200–1400 ms postonset. The TD group was more likely to be fixated on target. These differences were maintained after adjusting for language, verbal and nonverbal IQ, and attention scores. An analysis using parent report of autistic‐like behaviors showed higher scores to be associated with lower proportions of looking time at target, regardless of group. Further analysis showed fixation for the TD group to be significantly faster than for the ASD‐S. In addition, incremental processing was found for all groups. The study findings suggest that severity of autistic behaviors will impact significantly on childrens language processing in real life situations when exposed to syntactically complex material. They also show the value of using online methods for understanding how young children with ASD process language. Autism Res 2014, 7: 687–694.

Translational delivery of Cool Little Kids to prevent child internalising problems: randomised controlled trial

Objective: To determine whether a population-delivered parenting programme assists in preventing internalising problems at school entry for preschool children at-risk with temperamental inhibition. Methods: Design: a randomised controlled trial was used. Setting: the setting was 307 preschool services across eight socioeconomically diverse government areas in Melbourne, Australia. Participants: a total of 545 parents of inhibited 4-year-old children: 498 retained at 1-year follow up. Early intervention: Cool Little Kids parenting group programme was implemented. Primary outcomes: the primary outcomes were child DSM-IV anxiety disorders (assessor blind) and internalising problems. Secondary outcomes: the secondary outcomes were parenting practices and parent mental health. Results: At 1-year follow up (mean (standard deviation) age = 5.8 (0.4) years), there was little difference in anxiety disorders between the intervention and control arms (44.2% vs 50.2%; adjusted odds ratio = 0.86, 95% confidence interval = [0.60, 1.25], p = 0.427). Internalising problems were reduced in the intervention arm (Strengths and Difficulties Questionnaire: abnormal – 24.2% vs 33.0%; adjusted odds ratio = 0.56, 95% confidence interval = [0.35, 0.89], p = 0.014; symptoms – mean (standard deviation) = 2.5 (2.0) vs 2.9 (2.2); adjusted mean difference = –0.47, 95% confidence interval = [–0.81, –0.13], p = 0.006). Parents’ participation in the intervention was modest (29.4% attended most groups, 20.5% used skills most of the time during the year). A priori interaction tests suggested that for children with anxious parents, the intervention reduced anxiety disorders and internalising symptoms after 1 year. Conclusion: Offering Cool Little Kids across the population for inhibited preschoolers does not impact population outcomes after 1 year. Effects may be emerging for inhibited children at highest risk with parent anxiety. Trial outcomes will continue into mid-childhood.

Symptomatic response to testosterone treatment in dieting obese men with low testosterone levels in a randomized, placebo-controlled clinical trial

Background:Obese men commonly have reductions in circulating testosterone and report symptoms consistent with androgen deficiency. We hypothesized that testosterone treatment improves constitutional and sexual symptoms over and above the effects of weight loss alone.Methods:We conducted a pre-specified analysis of a randomized double-blind, placebo-controlled trial at a tertiary referral center. About 100 obese men (body mass index (BMI)⩾30 kg m−2) with a repeated total testosterone level ⩽12 nmol l−1 and a median age of 53 years (interquartile range 47–60) receiving 10 weeks of a very-low-energy diet (VLED) followed by 46 weeks of weight maintenance were randomly assigned at baseline to 56 weeks of intramuscular testosterone undecanoate (n=49, cases) or matching placebo (n=51, controls). Pre-specified outcomes were the between-group differences in Aging Male Symptoms scale (AMS) and international index of erectile function (IIEF-5) questionnaires.Results:Eighty-two men completed the study. At study end, cases showed significant symptomatic improvement in AMS score, compared with controls, and improvement was more marked in men with more severe baseline symptoms (mean adjusted difference (MAD) per unit of change in AMS score −0.34 (95% confidence interval (CI) −0.65, −0.02), P=0.04). This corresponds to improvements of 11% and 20% from baseline scores of 40 and 60, respectively, with higher scores denoting more severe symptoms. Men with erectile dysfunction (IIEF-5⩽20) had improved erectile function with testosterone treatment. Cases and controls lost the same weight after VLED (testosterone −12.0 kg; placebo −13.5 kg, P=0.40) and maintained this at study end (testosterone −11.4 kg; placebo −10.9 kg, P=0.80). The improvement in AMS following VLED was not different between the groups (−0.05 (95% CI −0.28, 0.17), P=0.65).Conclusions:In otherwise healthy obese men with mild to moderate symptoms and modest reductions in testosterone levels, testosterone treatment improved androgen deficiency symptoms over and above the improvement associated with weight loss alone, and more severely symptomatic men achieved a greater benefit.

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.