Hedonic and Homeostatic Appetite Control in Obesity and Type 2 Diabetes in the Context of Meal and Exercise Timing

The overall aim is to investigate effects of acute exercise on ad libitum energy intake and study whether this differs between morning and evening in individuals with overweight/obesity with or without type 2 diabetes (T2D). Furthermore, the aim is to examine the role of hedonic and homeostatic drivers of appetite control in obesity and T2D in the context of meal and exercise timing.

Fifty-eight adults (age 18 - 75 years old) with overweight/obesity (BMI \>25 kg/m2) and with/without T2D will participate in this randomized cross-over study. Participants will complete two visits in the morning and two in the evening with a minimum of 3 days washout. The visits will include ratings of subjective appetite and blood samples in the fasted state followed by either a 45 min exercise bout or rest for the same duration. 15 min after the termination of the exercise bout/rest period the participants will be presented with an ad libitum meal for assessment of energy intake (primary outcome). Then the participants will complete the Steno Biometric Food Preference Task (SBFPT); A computerized task measuring food choice, explicit liking, and implicit and explicit wanting with concomitant biometric measurements. Throughout the visits, subjective appetite will be rated using visual analogue scales and blood will be collected for assessment of appetite-related hormones and metabolites.

(Time: -60 minutes (fasting), -45 minutes (start exercise/rest), 0 minutes (finish exercise/rest), 15 minutes (ad libitum meal), 30 minutes (finish al libitum meal), 60 minutes (end of visit)

Descriptive data will be collected at a visit prior to the test days. These data include body weight (kg), Body Mass Index (BMI, kg/m2), fat mass (kg), fat free mass (kg), fat percentage (%), HbA1c (mmol/mol and %), waist circumference (cm), VO2-0peak and ECG. The participants will furthermore fill in questionnaires regarding the following: Socio-Economic Status (SES), Control Over Eating (CoEQ), Munich Chronotype Questionnaire (MCTQ), Physical Activity Questionnaires (IPAQ), Pittsburgh Sleep Quality Index (PSQI). In addition to the outcomes listed below, markers of liver function (Alanine aminotransferase (ALAT), Aspartate Transaminase (ASAT)), HbA1c, sodium, and potassium will be measured in the fasting state on the first morning visit.

The specific objectives are to:

1. Assess whether energy intake during an ad libitum meal differs after an acute bout of exercise compared to a rest condition
2. Assess whether energy intake during an ad libitum meal after an acute bout of exercise differs between morning and evening
3. Assess whether appetite ratings, food reward, and metabolic markers i.e., hormones and metabolites in response to an acute exercise bout and subsequent ad libitum meal differ between morning and evening
4. Examine if the above findings differ between individuals with and without T2D
5. Identify circulating biomarkers that can be used to stratify individuals with overweight/obesity into primary hedonic or homeostatic driven in terms of ad libitum food intake

Eligibility Criteria:
Inclusion Criteria:

* Adults with overweight or obesity (BMI \>25 kg/m2) with and without T2D
* HbA1c ≥48 mmol/mol for people with T2D

Exclusion Criteria:

* Not able to eat ad libitum meal
* Not able to perform the exercise bout
* Daily smoking
* For women: Pregnancy / planned pregnancy (within the study period) / lactating
* Self-reported history of an eating disorder in the past 3 years
* Self-reported weight change (\>5 kg) within three months prior to inclusion
* Treatment with antidepressants
* Treatment with fast acting insulin, combination insulin products and sulfonylureas
* Alcohol/drug abuse or in treatment with disulfiram (antabus) at time of inclusion
* Uncontrolled medical issues including but not limited to cardiovascular pulmonary, rheumatologic, hematologic, oncologic, infectious, gastrointestinal, or psychiatric disease; diabetes or other endocrine disease; immunosuppression
* Current treatment with medication which significantly affect appetite or energy balance (e.g., GLP-1 receptor agonists)
* Bariatric surgery
* Unable to understand the informed consent and the study procedures
* Concomitant participation in intervention studies
* Incapable of understanding Danish