title: Weight loss maintenance: physiological, psychological and clinical perspectives
Creators: name: Thom, George
Publisher: name: University of Glasgow
Year: 2020
Subjects: subject: obesity, weight loss maintenance, appetite hormones, adaptive thermogenesis, psychology, negative emotions.

description: Background: Decades of research have demonstrated that dietary-induced weight losses are rarely maintained in the long-term. The research described in this thesis aimed to contribute towards answering one big question - why is long-term weight loss maintenance (WLM) difficult to achieve for most people? A range of factors were examined including psychological, physiological and clinical/demographic influences. Aims: This thesis had four overarching aims: 1) To gain an in-depth understanding of weight loss and WLM experiences (study 1) 2) To integrate physiological and psychological perspectives to reach a broad view of WLM difficulties (study 2) 3) To investigate the role of appetite-related hormones in weight regain (study 3) 4) To investigate clinical and demographic predictors of type 2 diabetes remission and the role of weight loss (study 4) Methods: The four empirical chapters in this thesis are based on two distinct studies (‘Beyond’ and ‘DiRECT’). In both studies, individuals were recruited into a 2-year multi-component behavioural weight management programme. Weight loss was initiated by total diet replacement, which provided 825-853 kcal/day of liquid formula diet (shakes/soups) for up to 20 weeks, followed by ongoing visits designed to support long term WLM until 2-years. Both studies demonstrated average weight losses in the region of 15kg after total diet replacement, followed by varying degrees of weight regain over time. These studies therefore provide a suitable context to study the challenges of WLM. In study 1, a longitudinal qualitative design was used to investigate weight loss and WLM experiences around theoretical themes known to be important for behaviour change maintenance: motivation, self-regulation, habits, psychological resources and social/environmental influences. In study 2, a mixed-methods study design was used to evaluate the role of physiological and psychological factors in weight regain. The role of appetite-related hormones (GLP-1, ghrelin, PYY, leptin and GDF-15) and adaptive thermogenesis in weight regain were the specific focus. Resting metabolic rate was measured by indirect calorimetry and body composition was assessed by whole-body MRI. Findings were integrated alongside qualitative interview data from study 1. Studies 3 and 4 were post hoc analyses of the DiRECT study, investigating potential predictors of diabetes remission, weight loss and weight regain using multiple regression analyses. The role of appetite-related hormones (leptin, ghrelin, GLP-1 and PYY) was examined in study 3 and demographic and clinical influences were the focus of study 4. Results: In study 1, 64 interviews were completed over a 2-year period in 11 participants (median, n=6 per participant, range:4-8). Weight management experiences were individualised and the behavioural maintenance model used to anchor the analysis offered a fitting and broad framework to capture experiences. All theoretical themes (motives, self-regulation, habit, psychological resources and social/environmental influences) contributed towards understanding weight-related cognitions, behaviours and outcomes. Similarities and differences between Maintainers and Regainers were described and there was no single, common factor that seemed decisive in determining outcomes. Negative views of obesity were strong motivations for weight loss and WLM. 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 seemed to interfere with barrier identification and coping planning for both Maintainers and Regainers. Better long-term outcomes tended to be achieved by those with larger initial weight losses, which was linked to greater satisfaction and changes in self-perception In study 2, qualitative data from study 1 was integrated within a mixed-methods study design to present an analysis investigating the role of physiological and psychological factors in weight regain. Fasting GLP-1 concentration measured before and at maximal weight loss was negatively associated with weight regain. Adaptive reductions in thermogenesis were observed but did not associate with weight regain. Despite significant increases in ghrelin and reductions in GLP-1 and leptin these changes did not correspond to increases in subjective hunger, and on the contrary, participants often reported having a smaller appetite after weight loss during qualitative interviews. Individuals tended to perceive lapses and weight regain through the prism of stress and negative emotions. In study 3. the findings concerning GLP-1 from the study described above were investigated further, but not replicated, in a large cluster-randomised trial. However, the rise in fasting ghrelin (but not any other measured hormone) during weight loss between baseline and 12-months was a predictor of weight regain between 12 and 24 months. Concentration of ghrelin at 12-months also predicted subsequent weight regain, and ghrelin remained elevated over time despite weight-regain, which may suggest a compensatory drive to regain weight. This study provides further evidence to the hypothesis that physiological adaptations contribute to weight regain following diet-induced weight loss. In study 4, weight loss was found to be the best predictor of type 2 diabetes remission. This raised questions regarding predictors of weight loss, and WLM. Men were more successful at sustaining remission and weight losses over time. Higher anxiety/depression scores and antidepressant drug use were associated with poorer weight losses and remission outcomes. More frequent attendance predicted weight loss and remission. Weight loss achieved in the early weeks of treatment (by 4 weeks) was associated with remission status at 12 and 24-months, confirming evidence from other studies that those losing weight more rapidly achieve better long-term WLM outcomes. These findings provide evidence to clinicians, healthcare planners and to patients that diabetes remission is possible if adequate weight loss is achieved. Conclusions: Weight regain is a complex problem and improving outcomes requires a multi-faceted approach. By integrating methodologies within the same study populations a broad understanding of WLM and its difficulties was reached. To lose and maintain weight losses in the long-term requires a combination of motivation, support, self-regulation and an investment of time and energy to adhere to healthy lifestyle behaviours. Findings from this thesis suggest that adherence to a reduced energy diet supporting WLM would be enhanced through intervention strategies addressing negative emotional states (e.g. from life stress, low mood/depression) and attenuating the rise in the hunger hormone ghrelin, which occurs in response to significant diet-induced weight loss and is likely to increase the drive to eat.