Joint associations of diet and physical activity with incident type 2 diabetes and hypertension: an analysis of 144,288 UK Biobank participants.

BACKGROUND: Studies examining the joint associations of lifestyle exposures can reveal novel synergistic and joint effects, but no study has examined the joint association of diet and physical activity (PA) with type 2 diabetes (T2D) and hypertension. The aim of this study is to examine the joint associations of PA and diet with incidence of type T2D and hypertension, as a combined outcome and separately in a large sample of UK adults. METHODS: This prospective cohort study included 144,288 UK Biobank participants aged 40-69. Moderate to vigorous PA (MVPA) was measured using the International Physical Activity Questionnaire and a wrist accelerometer. We categorised PA and diet indicators (diet quality score (DQS) and energy intake (EI)) based on tertiles and derived joint PA and diet variables. Outcome was major cardiometabolic disease incidence (combination of T2D and hypertension). RESULTS: A total of 14,003(7.1%) participants developed T2D, 28,075(19.2%) developed hypertension, and 30,529(21.2%) developed T2D or hypertension over a mean follow-up of 10.9(3.7) years. Participants with middle and high self-reported MVPA levels had lower risk of major cardiometabolic disease regardless of diet, e.g. among high DQS group, hazard ratios in middle and high MVPA group were 0.90 (95%CI:0.86-0.94), and 0.88(95%CI:0.84-0.92), respectively. Participants with jointly high device-measured MVPA and high DQS levels had lower major cardiometabolic disease risk (HR: 0.84, 95%CI:0.71-0.99). The equivalent joint device-measured MVPA and EI exposure analyses showed no clear pattern of associations with the outcomes. CONCLUSION: Higher PA is an important component in cardiometabolic disease prevention across all diet quality and total EI groups. The observed lack of association between diet health outcomes may stem from a lower DQS.

A systematic review with meta-analyses of the relationship between recurrent binge eating and sleep parameters.

BACKGROUND: Sleep problems are known to compound the negative effects of other health issues, such as eating disorders and the associated behavior of binge eating. Previous studies suggested associations between binge eating and sleep problems, but the strength of the relationship is unknown. METHODS: We conducted a systematic review with meta-analyses examining the relationship between binge eating and sleep parameters. We searched for studies in Scopus, PubMed, and PsycInfo. The quality of evidence, including risk of bias, was assessed with adaptations of the Newcastle-Ottawa Scale and the Joanna Briggs Institute Critical Appraisal Checklist for Quasi-Experimental Studies, depending on study design. Data was synthesized as the difference in sleep between people who did or did not have binge eating. RESULTS: Thirty-one reports of studies met our eligibility criteria. Results are presented in 12 meta-analyses. In the 7 reports of studies (with 4448 participants) that assessed poor overall sleep quality, we found poorer overall sleep quality in people with binge eating compared to people without binge eating, with a standardized mean difference of 0.77 (95% confidence interval [CI] 0.61-0.92; P < 0.001), which is a large effect size. In addition, we found evidence that people with binge eating had significantly greater hypersomnia/daytime sleepiness (7 reports of studies with 4370 participants), insomnia (5 reports of studies with 12,733 participants), and difficulty falling asleep (3 reports of studies with 4089 participants) compared to people without binge eating, with moderate effect sizes (standardized mean differences of 0.57-0.66). CONCLUSIONS: People with binge eating exhibit poorer overall sleep quality compared to people without binge eating, and may also exhibit greater hypersomnia/daytime sleepiness, insomnia, and difficulty falling asleep. It is recommended that healthcare professionals routinely screen for poor overall sleep quality when treating people with binge eating-and address sleep difficulties when present.

Researchers in rheumatology should avoid categorization of continuous predictor variables.

BACKGROUND: Rheumatology researchers often categorize continuous predictor variables. We aimed to show how this practice may alter results from observational studies in rheumatology. METHODS: We conducted and compared the results of two analyses of the association between our predictor variable (percentage change in body mass index [BMI] from baseline to four years) and two outcome variable domains of structure and pain in knee and hip osteoarthritis. These two outcome variable domains covered 26 different outcomes for knee and hip combined. In the first analysis (categorical analysis), percentage change in BMI was categorized as ≥ 5% decrease in BMI, < 5% change in BMI, and ≥ 5% increase in BMI, while in the second analysis (continuous analysis), it was left as a continuous variable. In both analyses (categorical and continuous), we used generalized estimating equations with a logistic link function to investigate the association between the percentage change in BMI and the outcomes. RESULTS: For eight of the 26 investigated outcomes (31%), the results from the categorical analyses were different from the results from the continuous analyses. These differences were of three types: 1) for six of these eight outcomes, while the continuous analyses revealed associations in both directions (i.e., a decrease in BMI had one effect, while an increase in BMI had the opposite effect), the categorical analyses showed associations only in one direction of BMI change, not both; 2) for another one of these eight outcomes, the categorical analyses suggested an association with change in BMI, while this association was not shown in the continuous analyses (this is potentially a false positive association); 3) for the last of the eight outcomes, the continuous analyses suggested an association of change in BMI, while this association was not shown in the categorical analyses (this is potentially a false negative association). CONCLUSIONS: Categorization of continuous predictor variables alters the results of analyses and could lead to different conclusions; therefore, researchers in rheumatology should avoid it.

Eating Disorders In weight-related Therapy (EDIT) Collaboration: rationale and study design.

The cornerstone of obesity treatment is behavioural weight management, resulting in significant improvements in cardio-metabolic and psychosocial health. However, there is ongoing concern that dietary interventions used for weight management may precipitate the development of eating disorders. Systematic reviews demonstrate that, while for most participants medically supervised obesity treatment improves risk scores related to eating disorders, a subset of people who undergo obesity treatment may have poor outcomes for eating disorders. This review summarises the background and rationale for the formation of the Eating Disorders In weight-related Therapy (EDIT) Collaboration. The EDIT Collaboration will explore the complex risk factor interactions that precede changes to eating disorder risk following weight management. In this review, we also outline the programme of work and design of studies for the EDIT Collaboration, including expected knowledge gains. The EDIT studies explore risk factors and the interactions between them using individual-level data from international weight management trials. Combining all available data on eating disorder risk from weight management trials will allow sufficient sample size to interrogate our hypothesis: that individuals undertaking weight management interventions will vary in their eating disorder risk profile, on the basis of personal characteristics and intervention strategies available to them. The collaboration includes the integration of health consumers in project development and translation. An important knowledge gain from this project is a comprehensive understanding of the impact of weight management interventions on eating disorder risk.

Is binge eating associated with poor weight loss outcomes in people with a high body weight? A systematic review with meta-analyses.

OBJECTIVES: This systematic review aimed to compare the weight change in people with or without binge eating who underwent various weight loss treatments. METHODS: We searched for studies in PubMed, American Psychological Association, and Embase from inception to January 2022. The studies selected included assessment of binge eating and body weight before and after weight loss treatment in people of any age. The meta-analyses were conducted using Comprehensive Meta-Analysis (CMA). We used Egger's regression test, the funnel plot, and the Trim and Fill test to assess the risk of publication bias. RESULTS: Thirty-four studies were included in the systematic review, with a total of 10.184 participants. The included studies were divided into three categories according to types of weight loss treatments, namely, (1) bariatric surgery; (2) pharmacotherapy isolated or combined with behavioral interventions; and (3) behavioral and/or nutritional interventions. The meta-analyses showed no significant difference in weight loss between people with or without binge eating engaged in weight loss treatments, with an overall effect size of - 0.117 (95% CI - 0.405 to 0.171; P = 0.426). CONCLUSIONS: Our findings showed no difference in weight loss in people with or without pre-treatment binge eating who received various weight loss treatments. Weight loss treatments should not be withheld on the basis that they will not be effective in people with pre-treatment binge eating, albeit their safety and longer term impacts are unclear. LEVEL OF EVIDENCE: Level I, at least one properly designed randomized controlled trials; systematic reviews and meta-analyses; experimental studies.

Weight loss is associated with reduced risk of knee and hip replacement: a survival analysis using Osteoarthritis Initiative data.

OBJECTIVE: To describe the association between body weight change and the risk of knee replacement and hip replacement. DESIGN: Time-to-event survival analysis from a population-based cohort of participants who had or were at risk of clinically significant knee osteoarthritis at baseline. SETTING: Data from the Osteoarthritis Initiative (OAI), which collected data from four clinical centres in the United States. PARTICIPANTS: A total of 8069 knees from 4081 participants, and 8076 hips from 4064 participants (59.3% female) aged 45-79 years, with mean ± SD body mass index (BMI) of 28.7 ± 4.8 kg/m2, were included in the knee and hip analyses, respectively. EXPOSURE: Body weight change from baseline as a percentage of baseline at repeated follow-up visits over 8 years. MAIN OUTCOME MEASURE: Incidence of primary knee or hip replacement during 8-year follow-up. RESULTS: Body weight change had a small, positive, linear association with the risk of knee replacement (adjusted hazard ratio [HR] 1.02; 95% confidence interval [CI] 1.00-1.04). Body weight change was also positively and linearly associated with the risk of hip replacement in hips that were persistently painful at baseline (adjusted HR 1.03; 95% CI 1.01-1.05), but not in hips that were not persistently painful at baseline. There were no significant interactions between body weight change and baseline BMI in the association with knee or hip replacement. CONCLUSIONS: In people with or at risk of clinically significant knee osteoarthritis, every 1% weight loss was associated with a 2% reduced risk of knee replacement and - in those people who also had one or more persistently painful hips - a 3% reduced risk of hip replacement, regardless of baseline BMI. Public health strategies that incorporate weight loss interventions have the potential to reduce the burden of knee and hip replacement surgery.

Physical and mental health outcomes of an integrated cognitive behavioural and weight management therapy for people with an eating disorder characterized by binge eating and a high body mass index: a randomized controlled trial.

BACKGROUND: Bulimia nervosa (BN) and binge eating disorder (BED) are eating disorders (EDs) characterized by recurrent binge eating. They are associated with medical complications, impaired adaptive function and often a high BMI, for which a multidisciplinary treatment approach may be needed. This study explored the efficacy of a novel intervention integrating Cognitive Behavioural Therapy- Enhanced (CBT-E) and weight management for people with recurrent binge eating episodes and high BMI with respect to physical, psychopathological and quality of life outcomes. METHODS: Ninety-eight adults diagnosed with BN, BED, or Other Specified/Unspecified Feeding or Eating Disorder (OSFED/UFED) and BMI ≥ 27 to <40 kg/m2 were randomized to a multidisciplinary approach, the Healthy APproach to weIght management and Food in Eating Disorders (HAPIFED) or to CBT-E. Metabolic parameters, health-related quality of life, general psychological and ED symptoms and ED diagnostic status outcomes are reported. Data were analyzed with mixed effects models adopting multiple imputed datasets where data were missing. RESULTS: Both HAPIFED and CBT-E showed statistical significance for the time effect, with reduction in stress (p < 0.001), improvement in mental health-related quality of life (p = 0.032), reduction in binge eating severity (p < 0.001), and also in global ED symptoms scores (p < 0.001), with the significant changes found at end of treatment and sustained at 12-month follow-up. However, no statistical significance was found for differences between the interventions in any of the outcomes measured. Despite a high BMI, most participants (> 75%) had blood test results for glucose, insulin, triglycerides and cholesterol within the normal range, and 52% were within the normal range for the physical component of quality of life at baseline with no change during the trial period. CONCLUSION: Integrating weight and ED management resulted in comparable outcomes to ED therapy alone. Although adding weight management to an ED intervention had no adverse effects on psychological outcomes, it also had no beneficial effect on metabolic outcomes. Therefore, more intense weight management strategies may be required where indicated to improve metabolic outcomes. Safety will need to be concurrently investigated. TRIAL REGISTRATION: US National Institutes of Health clinical trial registration number NCT02464345 , date of registration 08/06/2015. Changes to the present paper from the published protocol paper (Trials 18:578, 2015) and as reported in the Trial registration (clinicaltrials.gov) are reported in Supplementary File 1.

Efficacy of dietary supplements containing isolated organic compounds for weight loss: a systematic review and meta-analysis of randomised placebo-controlled trials.

BACKGROUND/OBJECTIVES: A systematic review with meta-analysis was conducted to synthesise evidence on the efficacy of dietary supplements containing isolated organic compounds for weight loss. SUBJECTS/METHODS: Four electronic databases (Medline, Embase, Web of Science, Cinahl) were searched until December 2019. Sixty-seven randomised placebo-controlled trials of dietary supplements containing isolated organic compounds for weight loss were included. Meta-analyses were conducted for chitosan, glucomannan, conjugated linoleic acid and fructans, comparing mean weight difference post-intervention between participants receiving the dietary supplement or placebo. RESULTS: Statistically significant weight differences compared to placebo were observed for chitosan (-1.84 kg; 95% confidence interval [CI] -2.79, -0.88; p < 0.01), glucomannan (-1.27 kg; 95%CI -2.45, -0.09; p = 0.04), and conjugated linoleic acid (-1.08 kg; 95%CI -1.61, -0.55; p < 0.01). None met our threshold for clinical significance (≥2.5 kg). There was no statistically significant effect on weight for fructans compared to placebo (p = 0.24). For dietary supplements with an inadequate number of trials for meta-analysis, a statistically and borderline clinically significant weight difference compared to placebo was found for modified cellulose, manno-oligosaccharides (in males), blood orange juice extract, and three multiple-ingredient dietary supplements. These were only reported in one trial of each. Thus, more evidence is needed before recommending them for weight loss. CONCLUSIONS: While some dietary supplements containing isolated organic compounds warrant further investigation to determine efficacy and safety, there is currently insufficient evidence to recommend any of these dietary supplements for weight loss.

Does weight loss reduce the incidence of total knee and hip replacement for osteoarthritis?-A prospective cohort study among middle-aged and older adults with overweight or obesity.

OBJECTIVE: This study aims to investigate the association between weight change and total knee or hip replacement (TKR or THR) for OA among middle-aged and older adults with overweight or obesity. METHOD: Weight data were collected in 2006-2009 and in 2010 from the 45 and Up Study-a population-based cohort aged ≥45 years in New South Wales, Australia. Participants were included if they had a baseline body mass index (BMI) ≥ 25 kg/m2 and no history of TKR or THR. Weight change was categorised into four groups: >7.5% loss; >5-7.5% loss; stable (≤5% change) and >5% gain. Hospital admission data were linked to identify TKR and THR for OA, and multivariable Cox regression was used to assess risk of TKR and THR. RESULTS: Of 23,916 participants, 2139 lost >7.5% weight, 1655 lost 5-7.5% weight, and 4430 gained >5% weight. Over 5.2 years, 1009 (4.2%) underwent TKR and 483 (2.0%) THR. Compared to weight-stable, weight loss of >7.5% was associated with reduced risk of TKR after adjusting for age, sex, BMI, socioeconomic and lifestyle factors (hazard ratio 0.69, 95%CI 0.54-0.87), but had no association with THR. Weight loss of 5-7.5% was not associated with altered risk of either TKR or THR. Weight gain was associated with increased risk of THR after adjusting for confounders, but not TKR. CONCLUSION: This study suggests that a weight loss target >7.5% is required to reduce the risk of TKR in adults with overweight or obesity. Weight gain should be avoided as it increases the risk of THR.

Diet Quality following Total Meal Replacement Compared with Food-Based Weight-Loss Diets in Postmenopausal Women with Obesity: A Secondary Analysis of the TEMPO Diet Trial.

BACKGROUND: Severely energy-restricted diets that utilize meal-replacement products are the most effective dietary treatment for obesity. However, there are concerns they may fail to educate individuals on how to adopt a healthy food-based diet after weight loss. OBJECTIVES: The aim of this research was to compare changes in diet quality following total meal replacement compared with food-based weight-loss diets. METHODS: In this secondary analysis of a randomized controlled trial, 79 postmenopausal women aged 45-65 y, with a BMI (in kg/m2) of 30-40, were randomly assigned to either a total meal-replacement diet (energy intake restricted by 65-75% relative to requirements) for 16 wks, followed by a food-based diet (energy intake restricted by 25-35% relative to requirements) until 52 wks, or the food-based diet for the entire 52-wk period. Diet quality was scored at baseline and 52 wks using the Healthy Eating Index for Australian Adults, with score changes compared between groups using an independent t test. RESULTS: Diet quality improved from baseline in both groups, but less so in the total meal-replacement group, with a mean (SD) increase of 3.6 (10.8) points compared with 11.8 (13.9) points in the food-based group, resulting in a mean between-group difference of -8.2 (P = 0.004; 95% CI: -13.8, -2.7) points. This improvement in diet quality within both groups was mostly driven by a reduction in the intake of discretionary foods. Intake remained below the recommendations at 52 wks for 4 of the 5 food groups in both dietary interventions. CONCLUSIONS: In postmenopausal women with obesity, weight-loss interventions that involve either a total meal-replacement diet or a food-based diet both improve diet quality, however, not sufficiently to meet recommendations. This highlights the importance of addressing diet quality as a part of all dietary weight-loss interventions. This trial is registered with the Australia and New Zealand Clinical Trials Registry as 12612000651886.

Integrated weight loss and cognitive behavioural therapy (CBT) for the treatment of recurrent binge eating and high body mass index: a randomized controlled trial.

PURPOSE: The association between binge eating and obesity is increasing. Treatments for disorders of recurrent binge eating comorbid with obesity reduce eating disorder (ED) symptoms, but not weight. This study investigated the efficacy and safety of introducing a weight loss intervention to the treatment of people with disorders of recurrent binge eating and a high body mass index (BMI). METHODS: A single-blind randomized controlled trial selected adults with binge eating disorder or bulimia nervosa and BMI ≥ 27 to < 40 kg/m2. The primary outcome was sustained weight loss at 12-month follow-up. Secondary outcomes included ED symptoms. Mixed effects models analyses were conducted using multiple imputed datasets in the presence of missing data. RESULTS: Ninety-eight participants were randomized to the Health Approach to Weight Management and Food in Eating Disorders (HAPIFED) or to the Cognitive Behavioural Therapy-Enhanced (CBT-E). No between-group differences were found for percentage of participants achieving weight loss or secondary outcomes, except for reduction of purging behaviour, which was greater with HAPIFED (p = 0.016). Binge remission rates specifically at 12-month follow-up favoured HAPIFED (34.0% vs 16.7%; p = 0.049). Overall, significant improvements in the reduction of ED symptoms were seen in both groups and these were sustained at the 12-month follow-up. CONCLUSION: HAPIFED was not superior to CBT-E in promoting clinically significant weight loss and was not significantly different in reducing most ED symptoms. No harm was observed with HAPIFED, in that no worsening of ED symptoms was observed. Further studies should test approaches that target both the management of ED symptoms and the high BMI. LEVEL OF EVIDENCE: Level I, randomized controlled trial TRIAL REGISTRATION: US National Institutes of Health clinical trial registration number NCT02464345, date of registration 1 June 2015.

Effectiveness of herbal medicines for weight loss: A systematic review and meta-analysis of randomized controlled trials.

AIM: To update the available evidence on the efficacy and safety of complementary medicines to assist in weight loss by conducting a systematic review and meta-analysis of herbal medicines for weight loss. METHODS: Four electronic databases (Medline, Embase, CINAHL and Web of Science) were searched from inception until August 2018. A total of 54 randomized placebo-controlled trials of healthy overweight or obese adults were identified. Meta-analyses were conducted for herbal medicines with ≥4 studies available. Weight differences of ≥2.5 kg were considered clinically significant. RESULTS: As a single agent, only Phaseolus vulgaris resulted in a statistically significant weight loss compared to placebo, although this was not considered clinically significant. No effect was seen for Camellia sinensis or Garcinia cambogia. Statistically, but not clinically, significant differences were observed for combination preparations containing C. sinensis, P. vulgaris or Ephedra sinica. Of the herbal medicines trialled in ≤3 randomized controlled trials, statistically and clinically significant weight loss compared to placebo was reported for Irvingia gabonensis, Cissus quadrangularis, and Sphaeranthus indicus combined with Garcinia mangostana, among others, but these findings should be interpreted cautiously because of the small number of studies, generally poor methodological quality, and poor reporting of the herbal medicine interventions. Most herbal medicines appeared safe for consumption over the short duration of the studies (commonly ≤12 weeks). Some warrant further investigation to determine effect size, dosage and long-term safety. CONCLUSION: There is currently insufficient evidence to recommend any of the herbal medicines for weight loss included in the present review.

An investigation of relationships between disordered eating behaviors, weight/shape overvaluation and mood in the general population.

Disordered eating behaviors and cognitions have been extensively examined in samples of individuals with eating disorders, as well as in non-clinical samples. However, such examinations are lacking in the general population. We investigated disordered eating behaviors and cognitions in a community representative sample of 6052 participants in South Australia, aged 15-99 years. Participants were interviewed regarding weight/shape overvaluation, strict dieting, binge eating, purging, low mood and body mass index (BMI). Linear and logistic regression analyses were used to estimate the direct effects between these features. Steiger's Z test was used to compare the difference between the semi-partial associations of low mood and strict dieting with binge eating. Our findings suggest that similar relationships between strict dieting, low mood, purging and binge eating to those shown in the trans-diagnostic cognitive-behavioral model of eating disorders in clinical samples occur in the general community. However, in the general population, strict dieting was associated with elevated BMIs (and not with low BMIs as predicated by the model). Although this study does not ascertain any causal relationships in the observed associations, public health messages or services for weight reduction in people with higher body weights could potentially benefit from integration with messages addressing mood disorders and purging, in order to reduce potential adverse effects on disordered eating behaviors.

Effect of resistance training on liver fat and visceral adiposity in adults with obesity: A randomized controlled trial.

AIM: Regular aerobic exercise reduces visceral adipose tissue (VAT) and liver fat, however, not all individuals are able to adopt and adhere to such programs. Progressive resistance training (PRT) may be an alternative therapy, but there is limited available evidence. We examined the efficacy of PRT as per current exercise guidelines, compared with sham exercise placebo on liver fat and VAT. METHODS: Twenty-nine inactive and overweight/obese (body mass index ≥25 kg/m2 ) adults (age 29-59) were randomized to receive 8 weeks of PRT (n = 15, 10 exercises per session, 8-12 repetitions, 2-3 sets per exercise at 80-85% of one-repetition maximum, 3 days per week) or a sham exercise placebo control (CON) (n = 14). Change in liver fat, VAT, and abdominal s.c. adipose tissue (SAT) were assessed by magnetic resonance spectroscopy and imaging). RESULTS: There were no significant group by time interactions for change in liver fat in PRT versus CON groups (-0.07 ± 0.31% vs. 0.55 ± 0.77%, respectively, P = 0.19), VAT (-175 ± 85 cm3 vs. 10 ± 64 cm3 , respectively, P = 0.11), or abdominal SAT (-436 ± 245 cm3 vs. 127.29 ± 182 cm3 , respectively, P = 0.10) despite a significant increase in muscle volume (55 ± 78 cm3 vs. -0.04 ± 8 cm3 , respectively, P = 0.03). CONCLUSION: Traditional PRT is not effective for reducing liver fat in overweight/obese adults compared with placebo control. Although PRT has known metabolic benefits, an adequate volume of aerobic exercise should be promoted if liver fat is the therapeutic target.

Effect of aerobic exercise training dose on liver fat and visceral adiposity.

BACKGROUND & AIMS: Aerobic exercise reduces liver fat and visceral adipose tissue (VAT). However, there is limited data from randomized trials to inform exercise programming recommendations. This study examined the efficacy of commonly prescribed exercise doses for reducing liver fat and VAT using a randomized placebo-controlled design. METHODS: Inactive and overweight/obese adults received 8 weeks of either; i) low to moderate intensity, high volume aerobic exercise (LO:HI, 50% VO 2peak, 60 min, 4d/week); ii) high intensity, low volume aerobic exercise (HI:LO, 70% VO 2peak, 45 min, 3d/week); iii) low to moderate intensity, low volume aerobic exercise (LO:LO, 50% VO 2peak, 45 min, 3d/week); or iv) placebo (PLA). Liver fat (spectroscopy) and VAT (magnetic resonance imaging) were measured before and after intervention. RESULTS: Forty-seven of the 48 (n = 12 in each group) participants completed the trial. There were no serious adverse events. There was a significant change in group × time interaction in liver fat, which reduced in HI:LO by 2.38 ± 0.73%, in LO:HI by 2.62 ± 1.00%, and in LO:LO by 0.84 ± 0.47% but not in PLA (increase of 1.10 ± 0.62%) (p = 0.04). There was a significant reduction in VAT in HI:LO (-258.38 ± 87.78 cm(3)), in LO:HI (-386.80 ± 119.5 cm(3)), and in LO:LO (-212.96 ± 105.54 cm(3)), but not in PLA (92.64 ± 83.46 cm(3)) (p = 0.03). There were no significant differences between the dose or intensity of the exercise regimen and reductions in liver fat or VAT (p > 0.05). CONCLUSION: The study found no difference in efficacy of liver fat reduction by either aerobic exercise dose or intensity. All of the aerobic exercise regimens employed reduced liver fat and VAT by a small amount without clinically significant weight loss.

Tumor-induced anorexia and weight loss are mediated by the TGF-beta superfamily cytokine MIC-1.

Anorexia and weight loss are part of the wasting syndrome of late-stage cancer, are a major cause of morbidity and mortality in cancer, and are thought to be cytokine mediated. Macrophage inhibitory cytokine-1 (MIC-1) is produced by many cancers. Examination of sera from individuals with advanced prostate cancer showed a direct relationship between MIC-1 abundance and cancer-associated weight loss. In mice with xenografted prostate tumors, elevated MIC-1 levels were also associated with marked weight, fat and lean tissue loss that was mediated by decreased food intake and was reversed by administration of antibody to MIC-1. Additionally, normal mice given systemic MIC-1 and transgenic mice overexpressing MIC-1 showed hypophagia and reduced body weight. MIC-1 mediates its effects by central mechanisms that implicate the hypothalamic transforming growth factor-beta receptor II, extracellular signal-regulated kinases 1 and 2, signal transducer and activator of transcription-3, neuropeptide Y and pro-opiomelanocortin. Thus, MIC-1 is a newly defined central regulator of appetite and a potential target for the treatment of both cancer anorexia and weight loss, as well as of obesity.

Association of long-term use of non-steroidal anti-inflammatory drugs with knee osteoarthritis: a prospective multi-cohort study over 4-to-5 years.

This study examines the long-term impact of non-steroidal anti-inflammatory drugs (NSAIDs) on the progression of symptoms and structural deterioration of the joint in knee osteoarthritis. The study analyzes data from 4197 participants (8394 knees) across the Osteoarthritis Initiative (OAI), Multicenter Osteoarthritis Study (MOST), and Cohort Hip and Cohort Knee (CHECK) over 4-to-5 years. Adjustments were made for major covariates. We focussed on binary outcomes to assess the presence or absence of significant changes. We found that, relative to non-users, individuals using NSAIDs long-term were significantly more likely to experience aggravated symptoms exceeding the minimally clinically important difference, specifically, pain (OR: 2.04, 95% CI: 1.66-2.49), disability (OR: 2.21, 95% CI: 1.74-2.80), and stiffness (OR: 1.58, 95% CI: 1.29-1.93). Long-term users also faced a higher probability than non-users of having total knee replacement (OR: 3.13, 95% CI: 2.08-4.70), although no significant difference between long-term users and non-users was observed for structural deterioration in the knee joint (OR: 1.25, 95% CI: 0.94-1.65). While acknowledging the limitations of this study due to its observational design and the potential for bidirectional causality, these findings suggest that long-term NSAID use could accelerate the progression to total knee replacement by markedly exacerbating symptoms.

Evaluation of a measure of end-stage knee osteoarthritis compared to total knee replacement: An observational study using multicohort data.

OBJECTIVES: To determine if an end-stage knee osteoarthritis (esKOA) measure, based on symptomatic and radiographic criteria, can indicate progression to severe KOA earlier and with fewer research participants than total knee replacement (TKR). We employed both interventional and observational study designs as examples to estimate the required sample sizes. EsKOA in a knee was declared if either of the following two conditions were met: 1) moderate, intense, or severe symptoms of KOA indicated by pain and disability measurement and severe KOA indicated by radiographically-assessed knee structure; 2) intense or severe symptoms of KOA indicated by pain and disability measurement and frequent knee pain with mild or moderate KOA as indicated by radiographically-assessed knee structure. METHODS: We examined the association between weight loss from baseline to 2-to-2.5-year and 4-to-5-year follow-ups and the odds of esKOA and TKR in 5,593 participants (10,357 knees) from the Osteoarthritis Initiative (OAI) and the Multicenter Osteoarthritis Study (MOST). We also estimated the sample sizes needed for interventional and observational study designs to detect a 10, 20, or 50% reduction in the incidence of esKOA and TKR. RESULTS: The association of weight loss with both esKOA and TKR was detected at the 4-to-5-year follow-up. However, at the 2-to-2.5-year follow-up, the association was detected for esKOA but not TKR. The required sample sizes for detecting associations of weight loss with the incidence of esKOA were 85% to 93% smaller than those for TKR at the 4-to-5-year and 2-to-2.5-year follow-ups, respectively. CONCLUSION: The esKOA measure enables shorter and smaller studies compared to using TKR as an outcome.

Association of Weight Loss and Weight Gain With Structural Defects and Pain in Hand Osteoarthritis: Data From the Osteoarthritis Initiative.

OBJECTIVE: Our aim was to define the association of weight change (weight loss or weight gain) with the incidence and progression of hand osteoarthritis (OA), assessed either by radiography or by pain, using data from the Osteoarthritis Initiative. METHODS: Among the 4,796 participants, we selected 4,598 participants, excluding those with cancer or rheumatoid arthritis or a body mass index under 18.5 kg/m2. We investigated the association of weight change with incidence and progression of radiographic hand OA and the development and resolution of hand pain. Using multivariable logistic regression, we investigated the association of weight change from baseline to the 4-year follow-up with the incidence and progression of radiographic hand OA at the 4-year follow-up. Additionally, multivariable repeated-measure mixed-effects logistic regression analyzed the association of weight change with the development and resolution of hand pain across 2-year, 4-year, 6-year, and 8-year follow-ups. RESULTS: No statistically significant associations were observed between weight change and the investigated outcomes. Specifically, for each 5% weight loss, the odds ratios for the incidence and progression of radiographic hand OA were 0.90 (95% confidence interval [95% CI] 0.67-1.23) and 0.92 (95% CI 0.84-1.00), respectively. Similarly, for each 5% weight loss, the odds ratios for the development and resolution of hand pain at the 8-year follow-up were 1.00 (95% CI 0.92-1.09) and 1.07 (95% CI 0.91-1.25), respectively. CONCLUSION: Our study found no evidence of an association between weight change and the odds of incidence or progression of radiographic hand OA over 4 years, nor the development or resolution of hand pain over 8 years.

Postprandial cardiac autonomic function in Prader-Willi syndrome.

CONTEXT: Individuals with Prader-Willi syndrome (PWS) have a high cardiovascular risk, the mechanism of which is unclear. There may be dysfunction in the autonomic nervous system (ANS) in PWS. OBJECTIVE: To measure, as indicators of cardiac autonomic function, postprandial heart rate variability (HRV) and arterial stiffness in adults with PWS. METHODS: Ten adults with PWS were compared with 11 matched healthy obese subjects and 9 healthy lean subjects. Electrocardiographic traces and arterial stiffness were recorded over a period of 10 minutes at -60, 0, 30, 60, 120 and 240 minutes after consumption of a standardized 600-kCal breakfast. Frequency domain analysis was performed using fast Fourier transform to estimate power spectral density in the full spectrum and in low-frequency (LF 0·04-0·15 Hz) and high-frequency (HF 0·15-0·40 Hz) bands. RESULTS: ANCOVA revealed a reduced LF HRV meal response in adults with PWS compared with obese controls, with no differences in HF HRV, LF/HF ratio, heart rate, total power or arterial stiffness meal responses. CONCLUSIONS: This study assessed cardiac autonomic function in adults with PWS compared with matched obese and lean subjects in response to a meal. Results suggest impaired postprandial ANS responsiveness in PWS, which could contribute to both the known increased cardiovascular risk and obesity.