How is appetite controlled in obesity and type 2 diabetes?

How is appetite controlled in obesity and type 2 diabetes?
– and what is the role of meal and exercise timing?

We know very little about the contributions of hedonic and homeostatic appetite control in people with obesity and type 2 diabetes and the role of meal and exercise timing.

Having just received a DKK three million grant from the novoSTAR programme at Novo Nordisk A/S, DDA-funded postdoc at Steno Diabetes Center Copenhagen, Jonas Salling Quist, and his colleagues want to change that.

- We want to investigate whether appetite and food reward in response to meals and exercise differ according to the time of day, and whether this is different in people with overweight and people with overweight and type 2 diabetes compared to people with normal weight. In collaboration with researchers from Novo Nordisk A/S, we also aim to identify new metabolic markers of appetite and food reward and to investigate the markers we already know are involved in appetite control and glucose metabolism, says Jonas Salling Quist.

Our brains may have different food preferences
Today, energy-rich high-fat sweet food is very easily accessible worldwide making us more likely to eat unhealthily. This is in itself a well-known problem.

- However, we know from observational studies that obesity is associated with preferences for energy-rich food high in fat and sugar. Furthermore, small brain imaging studies have suggested greater activity in central reward circuits in response to visual food stimuli and food intake in individuals with type 2 diabetes compared to healthy individuals. Insulin-reward pathways may be involved in this altered response as insulin resistance in the periphery is associated with insulin resistance in brain regions involved in control of appetite and reward in people with type 2 diabetes. However, it remains to be established whether obesity per se or type 2 diabetes alters food reward, and larger studies are needed to clarify this, says Jonas Salling Quist.

If hedonic and homeostatic aspects of appetite control are different in people with overweight and/or with overweight and type 2 diabetes compared to people with normal weight, this is important knowledge, which may be used to optimise prevention and treatment of metabolic diseases.

- This may, in part, explain why some people are more prone to becoming overweight and/or developing type 2 diabetes, says Jonas Salling Quist.

Jonas Salling Quist and his colleagues will also look at exercise in connection with appetite. Studies indicate that acute exercise suppresses appetite, but we know little about the mechanisms and whether the response is altered in obesity and type 2 diabetes.

Timing is everything – or is it?
Today, clinical guidelines in relation to overweight and related metabolic diseases are focused on “what” and “how much” to eat and “how” and “how much” to exercise. However, “when” to eat and exercise may be of great importance.

Our metabolism varies during the day. This means that our body reacts differently to a meal or to exercise performed in the morning compared to the afternoon or evening. People with normal weight have been found to be more glucose intolerant later in the day and, from a metabolic perspective, therefore better at handling food intake in the morning.

- Therefore, if you eat late in the evening or during the night, it is in misalignment with circadian rhythms in metabolism and you may be at greater risk of overweight and type 2 diabetes. In a previous study at Steno Diabetes Center Copenhagen, we observed that late-evening food intake was highly prevalent among individuals with type 2 diabetes. Previous studies have suggested that the circadian rhythm in insulin sensitivity among individuals with type 2 diabetes is different from individuals without diabetes which may affect the metabolic response to food intake and exercise during the day. However, we know very little about the diurnal pattern of appetite and metabolism in people with obesity and in people with overweight and type 2 diabetes, says Jonas Salling Quist.

Previous studies indicate that morning exercise leads to greater weight loss than afternoon/evening exercise in individuals with overweight but that exercise in the afternoon seems to be better for glycaemic control in individuals with type 2 diabetes compared with morning exercise.

- Therefore, we want to investigate the underlying mechanisms in relation to timing of exercise and food intake in obesity and type 2 diabetes, says Jonas Salling Quist.

Danish Diabetes Academy-funding made research path possible
This new study ‘The TIming of Meal and EXercise in obesity and type 2 diabetes (TIMEX) study’ is a continuation of the line of research that Jonas Salling Quist received DDA-funding for.

- Being funded by the DDA has given me the possibility to continue to work within the same line of research, which includes investigation of the role of timing of lifestyle factors including food intake and exercise in relation to appetite, obesity and type 2 diabetes. For that, I am very grateful, says Jonas Salling Quist.

The study is a collaboration between researchers from Clinical Prevention Research, Steno Diabetes Center Copenhagen: Jonas Salling Quist, Kristine Færch, Hanne Pedersen, Natja Launbo and Martin Bæk Blond Novo Nordisk: Marina Kjærgaard Gerstenberg and Rune Ehrenreich Kuhre and University of Leeds, UK: Graham Finlayson and Kristine Beaulieu. The project is a close collaboration with DDA-funded Visiting Professor Graham Finlayson and Visiting researcher Kristine Beaulieu, who are both affiliated with the Clinical Prevention Research group at Steno Diabetes Center Copenhagen.

Based on the close collaboration with Professor Graham Finlayson and Dr Kristine Beaulieu during the last years, Jonas Salling Quist has been invited to be affiliated as visiting researcher in their research group the Appetite Control and Energy Balance Research Group at University of Leeds which will further strengthen the collaboration on future studies in Leeds and at Steno Diabetes Center Copenhagen.

Jonas Salling Quist expects that the results from the ongoing time-restricted eating trial, RESET, which will be completed in March 2022, will be published later this year. This is also the case for the first phases (needs assessment and pilot study) of the DDA-funded RESET2 project in which Jonas Salling Quist and colleagues investigate time-restricted eating in the treatment of type 2 diabetes. The last and main phase of RESET2 is a large clinical trial which will start ultimo 2022. In addition to the DDA grant, Jonas Salling Quist and colleagues have received funding from the Novo Nordisk Foundation and the Danish Diabetes Association.