Biopsychology of appetite and energy balance within clinical diabetes prevention: Time-restricted eating in adults at risk of type 2 diabetes

Current prevention and treatment of obesity and type 2 diabetes (T2D) include energy-restricted diets and increased levels of physical activity, but adherence to such strategies is difficult, and maintenance is challenging for most individuals. Timing of food intake and fasting periods affect the circadian rhythms of metabolic organs (i.e. 'chrono-nutrition'), and experimental data from animal studies suggest promising effects of time-restricted eating on weight loss, glucose regulation, appetite and energy levels. Therefore, it is hypothesized that time-restricted eating, allowing dietary intake within a limited time interval during the day, will be an attractive, feasible and sustainable option for management of obesity and dysglycaemia.

To understand the underlying mechanisms for potential health effects, research at Steno Diabetes Centre Copenhagen (SDCC) aims to examine the effects of time-restricted eating on both metabolic and behavioural parameters in adults with overweight and obesity at high risk of developing T2D.

Chrono-nutrition is an emerging special interest within nutritional science and a crucial gap in the literature is to examine the interaction between exercise and meal timing on energy balance, and appetite and metabolic control in adults with obesity and T2D. By integrating my expertise in the biopsychology of appetite and energy balance with clinical approaches in T2D prevention, there is potential for synergistic impact on understanding and improving health. If this proposal is successful, the complementary training I will acquire at SDCC will address this gap in knowledge and expertise.

With this Award I will gain experience with clinical populations (i.e. individuals with (pre)diabetes) and in more complex physiological assessment of glucose regulation and metabolism. I will expand my skillset and be better trained to conduct multidisciplinary, mechanistic nutritional research across a range of populations addressing overlapping themes pertaining to appetite control, physical activity and chrono-nutrition.

I am at the career stage where I am seeking to catalyse my progression to an independent researcher and to obtain funding for a longer, larger fellowship award. This Travelling Skills Award is the ideal next step in my career as it will support me in acquiring knowledge and skills in a new discipline in order to address important questions in the field of nutrition.

Only a small number of human clinical studies have examined effect of time-restricted eating on body weight and cardiometabolic outcomes. The aim of the RESET trial being conducted at Steno Diabetes Centre Copenhagen (SDCC) is to investigate effects of 12 weeks of time-restricted eating on behaviour and metabolism in individuals with overweight or obesity at high risk of type 2 diabetes (T2D; clinicaltrials.gov NCT03854656).

With this Award, I will join the RESET trial and acquire new skills from clinical T2D prevention, such as physiological assessments of metabolic and inflammatory biomarkers relating to glycaemic control; meal tests; gastric emptying; biometric assessment of food preferences; and analytical techniques using 'R' statistical package. Further training and pilot work will be gained from a whole-room indirect calorimeter situated at University of Copenhagen for mechanistic assessment of energy expenditure and substrate oxidation in response to exercise and time-restricted eating.

This Award will place me in a strong position to conduct collaborative and multidisciplinary mechanistic nutrition research with a focus on behaviour and metabolism in populations living with obesity and T2D. I aspire to create and direct a scientific weight management research in the North of England that is world leading in the application of the biopsychology of appetite and energy balance, to obesity and T2D prevention. This multidisciplinary, collaborative perspective will extend my network beyond dietetics/psychology to include physicians, patients, biostatisticians and data scientists.

Who will benefit from this research?
This Award will strengthen the UK nutrition research base by integrating my nutrition-related science in the biopsychology of appetite and energy balance with clinical research in type 2 diabetes (T2D) prevention and treatment. By visiting the world-leading Steno Diabetes Centre Copenhagen (SDCC), I will learn about integrating nutritional research within a clinical environment. I will return to the Appetite Control and Energy Balance Research Group (ACEB) at the University of Leeds with a strong international partnership and skills to conduct rigorous and high-quality nutritional research to improve mechanistic understanding of obesity and T2D to optimise health outcomes. This will benefit nutritional research, clinical practice and policy in the UK and internationally with potential for food-nutrition-health coordination with food sciences, industry, and disease disciplines.

How will they benefit from this research?
SHORT-TERM IMPACT (0-2 years): Skills acquisition and protocol development to integrate within a longer, larger research fellowship application.
This Award will provide the opportunity to learn new skills in a new clinical research setting. We will develop novel protocols and standardized procedures for a multi-year, collaborative programme of research between University of Leeds and SDCC. The Award will end with a submission for a Sir Henry Wellcome Fellowship and MRC Career Development Award in April 2021 to examine the influence of meal and exercise timing on appetite, body weight and metabolic control in obesity and T2D.

MEDIUM-TERM IMPACT (2-5 years): Broadening of research approach, portfolio and partners.
This Award will enable a wider mechanistic approach to study nutrition in health and disease. This will open doors to conduct research with new partners in the region, the UK and internationally, and to target more funding opportunities for well-controlled experimental studies and nutritional interventions. Areas of research opportunities highlighted by the 2017 Review of Nutrition and Human Health Research that relate to this research include:
- Effect of biological rhythms on nutritional response
- Interplay between nutrients and regulatory networks controlling energy homeostasis
- Stratified/personalised nutrition
- Interaction between nutrition and physical activity across the life course
- Prevention-related mechanistic nutritional physiology
Future funding will be sought from New Investigator and/or Research Team Grants (MRC, BBSRC, NIHR) to address the above lines of inquiry.

LONG-TERM IMPACT (5-15 years): Conduct high-quality, collaborative research that translates understanding from basic science into clinical and applied settings.
I aspire to be a world-leader in the study of nutritional sciences, and direct a scientific weight management research centre in the North of England (e.g. MRC Centre or Unit, or NIHR Biomedical Research Unit). This would include a team of dietitians, exercise physiologists, psychologists, physicians, biostatisticians and data scientists to accelerate the impact of academic insights stemming from units such as the internationally renowned ACEB Research Group at University of Leeds to improve health and disease in the clinic and community. This integrated and coordinated infrastructure would be well equipped to support mechanistic research and student training in nutrition. Ultimately, the aim is to improve health through nutrition, train the next generation of nutritional scientists and dietitians, and promote the translation of evidence-based nutrition science into clinical practice and policy.