The role of appetite-related hormones, adaptive thermogenesis, perceived hunger and stress in long-term weight-loss maintenance: a mixed-methods study

Background/objectives: Weight-loss maintenance is challenging, and few succeed in the long term. This study aimed to explain how appetite-related hormones, adaptive thermogenesis, perceived hunger and stress influence weight-loss maintenance. Subjects/methods: Fifteen adult women (age, 46.3 ± 9.5 years; BMI, 39.4 ± 4.3 kg/m2) participated in a 24-month intervention, which included 3–5 months total diet replacement (825–853 kcal/d). Body weight and composition (Magnetic Resonance Imaging), resting metabolic rate (indirect calorimetry), and fasting plasma concentration of leptin, ghrelin, glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and growth differentiation factor 15 (GDF-15) were measured at baseline and after weight loss, around 6 months. Perceptions relating to weight-loss maintenance were explored using qualitative interviews. Results: Mean (SD) changes in body weight (−13.8 ± 6.3 kg) and total adipose tissue (−11.5 ± 4.9 kg) were significant (P < 0.001). Weight loss was associated with a significant reduction in resting metabolic rate (−291 ± 226 kcal/day, P < 0.001) and adaptive thermogenesis (−150 ± 162 kcal/day, P = 0.003), reduction in leptin (P < 0.001) and GLP-1 (P = 0.015), an increase in ghrelin (P < 0.001), and no changes in PYY and GDF-15. Weight regain between 6 and 24 months (6.1 ± 6.3 kg, P < 0.05) was correlated positively with change in GLP-1 (r = 0.5, P = 0.037) and negatively with GLP-1 at baseline (r = −0.7, P = 0.003) and after weight loss (r = −0.7, P = 0.005). Participants did not report increased hunger after weight loss, and stress-related/emotional eating was perceived as the main reason for regain. Conclusions: Weight regain is more likely with lower fasting GLP-1 and greater reduction in GLP-1 after weight loss, but psychological aspects of eating behaviour appear as important in attenuating weight-loss maintenance

UK dietitians' attitudes and experiences of formula very low- and low-energy diets in clinical practice

Despite evidence that formula very low-energy diets (VLED) and low-energy diets (LED) are both effective and safe as treatments for obesity and type 2 diabetes, these diets remain underutilized in the United Kingdom. The aim of this study was to explore UK dietitians' attitudes and experiences of using formula VLED and LED. A cross-sectional survey was disseminated between September 2019 and April 2020 through websites, social media platforms and dietetic networks using snowball sampling. In total, 241 dietitians responded to the online survey with 152 participants included in the final analysis (female [94.1%], mean age 40.8 years [SD 9.5]; median 12 years [interquartile range 8, 22] within dietetic practice). One hundred and nine (71.7%) participants reported currently using VLED/LED in clinical practice and 43 (28.3%) did not. Those with lower motivation and confidence in implementing VLED/LED in clinical practice were less likely to use them. Cost and adherence were the two highest reported barriers to use. Dietitians perceived VLED/LED were effective, but concerns remained about long-term effectiveness, particularly for some patient groups. Dietitians also reported that further education, funding and service infrastructure, including access to clinic space and administrative support, were required to help embed VLED/LED into routine clinical practice. With clinical services now regularly offering VLED/LED programmes in the United Kingdom, dietitians are ideally placed to provide long-term support. However, understanding, reporting and addressing the potential barriers (funding/infrastructure and education) appear to be key requirements in increasing the delivery of VLED/LED programmes nationally

The Diabetes Remission Clinical Trial (DiRECT): protocol for a cluster randomised trial

Background: Despite improving evidence-based practice following clinical guidelines to optimise drug therapy, Type 2 diabetes (T2DM) still exerts a devastating toll from vascular complications and premature death. Biochemical remission of T2DM has been demonstrated with weight loss around 15kg following bariatric surgery and in several small studies of non-surgical energy-restriction treatments. The non-surgical Counterweight-Plus programme, running in Primary Care where obesity and T2DM are routinely managed, produces >15 kg weight loss in 33 % of all enrolled patients. The Diabetes UK-funded Counterpoint study suggested that this should be sufficient to reverse T2DM by removing ectopic fat in liver and pancreas, restoring first-phase insulin secretion. The Diabetes Remission Clinical Trial (DiRECT) was designed to determine whether a structured, intensive, weight management programme, delivered in a routine Primary Care setting, is a viable treatment for achieving durable normoglycaemia. Other aims are to understand the mechanistic basis of remission and to identify psychological predictors of response. Methods/Design: Cluster-randomised design with GP practice as the unit of randomisation: 280 participants from around 30 practices in Scotland and England will be allocated either to continue usual guideline-based care or to add the Counterweight-Plus weight management programme, which includes primary care nurse or dietitian delivery of 12-20weeks low calorie diet replacement, food reintroduction, and long-term weight loss maintenance. Main inclusion criteria: men and women aged 20-65years, all ethnicities, T2DM 0-6years duration, BMI 27-45 kg/m2. Tyneside participants will undergo Magnetic Resonance (MR) studies of pancreatic and hepatic fat, and metabolic studies to determine mechanisms underlying T2DM remission. Co-primary endpoints: weight reduction ≥ 15 kg and HbA1c <48 mmol/mol at one year. Further follow-up at 2 years. Discussion: This study will establish whether a structured weight management programme, delivered in Primary Care by practice nurses or dietitians, is a viable treatment to achieve T2DM remission. Results, available from 2018 onwards, will inform future service strategy

‘I have been all in, I have been all out and I have been everything in-between’: a 2-year longitudinal qualitative study of weight-loss maintenance

Background: Qualitative studies investigating weight management experiences are usually cross‐sectional or of short duration, which limits understanding of the long‐term challenges. Methods: Eleven women [mean (SD) age 44.9 (9.8) years; body mass index 40.3 (4.0) kg m−2] participated in this longitudinal qualitative study, which included up to 20 weeks of total diet replacement (825–853 kcal day−1) and ongoing support for weight loss maintenance (WLM), to 2 years. Semi‐structured interviews were conducted at baseline and programme end, as well as at key intervals during the intervention. Questions examined five theoretical themes: motivation, self‐regulation, habits, psychological resources and social/environmental influences. Data were coded and analysed in nvivo (https://qsrinternational.com/nvivo) using the framework method. Results: In total, 64 interviews were completed (median, n = 6 per participant). Mean (SD) weight loss was 15.7 (9.6) kg (14.6% body weight) at 6 months and 9.6 (9.9) kg (8.8% body weight) at 2 years. The prespecified theoretical model offered a useful framework to capture the variability of experiences. Negative aspects of obesity were strong motivations for weight loss and maintenance. Perceiving new routines as sustainable and developing a ‘maintenance mindset’ was characteristic of ‘Maintainers’, whereas meeting emotional needs at the expense of WLM goals during periods of stress and negative mood states was reported more often by ‘Regainers’. Optimistic beliefs about maintaining weight losses appeared to interfere with barrier identification and coping planning for most participants. Conclusions: People tended to be very optimistic about WLM without acknowledging barriers and this may undermine longer‐term outcomes. The potential for regain remained over time, mainly as a result of emotion‐triggered eating to alleviate stress and negative feelings. More active self‐regulation during these circumstances may improve WLM, and these situations represent important targets for intervention

A total diet replacement weight management programme for difficult-to-treat asthma associated with obesity: a randomised controlled feasibility trial

Background: Obesity is often associated with uncontrolled, difficult-to-treat asthma and increased morbidity and mortality. Previous studies suggest that weight loss may improve asthma outcomes but with heterogenous asthma populations studied and unclear consensus on optimal method of weight management. The Counterweight-Plus weight management programme (CWP) is an evidence-based, dietitian-led, total diet replacement (TDR) programme. Research question: Can use of the CWP compared to usual care (UC) improve asthma control and quality of life in patients with difficult-to-treat asthma and obesity? Study design and methods: We conducted a 1:1 (CWP:UC) randomised, controlled single centre trial in adults with difficult-to-treat asthma and body mass index ≥30kg/m2. CWP: 12-week TDR phase (800kcal/day low-energy formula); stepwise food reintroduction and weight loss maintenance up to 1 year. Primary outcome: change in asthma control questionnaire (ACQ6) score over 16 weeks. Secondary outcome: change in asthma quality of life questionnaire (AQLQ) score. Results: 35 participants were randomised (36 screened) and 33 attended 16-week follow-up (17 CWP, 16 UC). Overall, mean (95%CI) ACQ6 at baseline was 2.8 (2.4, 3.1). Weight loss was greater in CWP than UC (mean difference -12.1kg; 95%CI -16.9, -7.4; p<0.001). ACQ6 improved more in CWP than UC (mean difference -0.69; 95%CI -1.37, -0.01; p=0.048). A larger proportion of participants achieved minimal clinically important difference in ACQ6 with CWP than UC (53% vs 19%; p=0.041; NNT 3 (95%CI 1.5, 26.9)). AQLQ improvement was greater in CWP than UC (mean difference 0.76; 95%CI 0.18, 1.34; p=0.013). Interpretation: Utilising a structured weight management programme results in clinically important improvements in asthma control and quality of life over 16 weeks compared to usual care, in adults with difficult-to-treat asthma and obesity. This generalisable programme is easy to deliver for this challenging phenotype. Longer-term outcomes continue to be studied

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Dietary weight-management for type 2 diabetes remissions in South Asians: the South Asian diabetes remission randomised trial for proof-of-concept and feasibility (STANDby)

Background: We aimed to assess whether a structured weight management programme incorporating a total diet replacement (TDR) (3–5 months ∼850 kcal/day formula diet) weight loss phase is acceptable to people of South Asian ethnicity and can achieve type 2 diabetes (T2D) remissions similarly to other populations. Methods: Adults of South Asian ethnicity, aged 18–65 years, with T2D for ≤4 years, and BMI 25–45 kg/m2 were recruited from primary care and social media, and randomised to commence TDR either immediately (iTDR), or delayed (dTDR) for 3–5 months as a usual care control arm during this period. Intervention effects were tested in randomised comparisons powered to detect significant weight loss, and in an expanded observational analysis to determine remission effect size, including both iTDR and dTDR groups. Acceptability in those recruited was explored by questionnaire and weight change. Trial registration: Current Controlled Trials, ISRCTN10720065. Date of Registration 27/09/2017. Findings: Twenty-five eligible individuals were recruited. Mean baseline (SD) age was 45.8 (11.1) years, weight 88.2 (13.7) kg, BMI 32.1 (3.8) kg/m2, HbA1c 60.4 (11.3) mmol/mol, liver fat by MRI 15.6 (9.4)%. In the RCT, mean(SD) weight change after TDR was −7.7 (7.2)% in the intervention group (n = 13), and −1.2 (1.4)% in the usual-care control group (n = 12) (p = 0.005), with T2D remission achieved by 5/13, compared to 0/12 respectively (p = 0.039). In the observational study, 23/25 started TDR and 19/23 participants completed the TDR phase. Median time spent in TDR was 105 days (IQR 77–134 days). T2D remission was achieved in 10/23 (43%), and weight changes were concordant with the RCT. Overall, 8/23 (35%) lost over 10% bodyweight. Absolute liver fat proportion near halved from 15.3% at the start of TDR to 8.6% (p < 0.001). Interpretation: In UK-based South Asians, TDR-led weight loss and T2D remission rates are comparable to those observed in white cohorts, and the intervention was acceptable in most of those recruited. There is potential to further improve outcomes, but one-third lost >10% body weight, and the mechanism underpinning T2D remission appears similar, driven by weight change with loss of excess ectopic body-fat. Funding: We gratefully acknowledge funding for the MRI scans from the, Miss MJM Smith Trust (registered charity: SC040586). No other external funds were provided for this trial. NS is supported by the British Heart Foundation Research Excellence Award (RE/18/6/34217)

The remote diet intervention to reduce Long COVID symptoms trial (ReDIRECT): protocol for a randomised controlled trial to determine the effectiveness and cost-effectiveness of a remotely delivered supported weight management programme for people with Long COVID and excess weight, with personalised improvement goals

Objectives: The Remote Diet Intervention to Reduce Long COVID Symptoms Trial (ReDIRECT) evaluates whether the digitally delivered, evidence-based, cost-effective Counterweight-Plus weight management programme improves symptoms of Long COVID in people with overweight/obesity. Methods: Baseline randomised, non-blinded design with 240 participants allocated in a 1:1 ratio either to continue usual care or to add the remotely delivered Counterweight-Plus weight management programme, which includes a Counterweight dietitian supported delivery of 12 weeks total diet replacement, food reintroduction, and long-term weight loss maintenance. Randomisation is achieved by accessing a web-based randomisation system incorporated into the study web portal developed by a registered Clinical Trials Unit. We are using an innovative approach to outcome personalisation, with each participant selecting their most dominant Long COVID symptom as their primary outcome assessed at six months. Participants in the control arm enter the weight management programme after six months. We are recruiting participants from social media and existing networks (e.g., Long COVID Scotland groups), through newspaper advertisements and from primary care. Main inclusion criteria: people with Long COVID symptoms persisting > three months, aged 18 years or above, body mass index (BMI) above 27kg/m2 (>25kg/m2 for South Asians). The trial includes a process evaluation (involving qualitative interviews with participants and analysis of data on dose, fidelity and reach of the intervention) and economic evaluation (within-trial and long-term cost-utility analyses). Anticipated results: The recruitment for this study started in December 2021 and ended in July 2022. Project results are not yet available and will be shared via peer-reviewed publication once the six-months outcomes have been analysed. Trial registration: Current Controlled Trials ISRCTN1259552

Participant experiences in the Diabetes REmission Clinical Trial (DiRECT).

INTRODUCTION: The Diabetes REmission Clinical Trial (DiRECT) has shown that sustained remission of type 2 diabetes in primary care is achievable through weight loss using total diet replacement (TDR) with continued behavioural support. Understanding participants' experiences can help optimise the intervention, support implementation into healthcare, and understand the process of behaviour change. METHODS: Thirty-four DiRECT participants were recruited into this embedded qualitative evaluation study. In-person and telephone interviews were conducted before the TDR; at week 6-8 of the TDR; 2 weeks into food reintroduction (FR); and at 1 year, to learn about participant experiences with the programme. Transcribed narratives were analysed thematically, and we used interpretation to develop overarching themes. RESULTS: Initiation of the TDR and transition to FR were challenging and required increased behavioural support. In general, adhering to TDR proved easier than the participants had anticipated. Some participants chose the optional extension of TDR. Rapid weight loss and changes in diabetes markers provided ongoing motivation. Further weight loss, behavioural support and occasional use of TDR facilitated weight loss maintenance (WLM). A process of behaviour adaptation to change following regime disruption was identified in three stages: (1) expectations of the new, (2) overcoming difficulties with adherence, and (3) acceptance of continuous effort and establishment of routines. CONCLUSIONS: The DiRECT intervention was acceptable and regularity, continuity, and tailoring of behavioural support was instrumental in its implementation in primary care. The adaptation process accounts for some of the individual variability of experiences with the intervention and highlights the need for programme flexibility