Exercise, Chronotype, and Prediabetes

Chronotype refers to an individual's circadian preferences for being active and fully functional at certain times of the day. Using validated questionnaires, individual's chronotype can be categorized to either a morning (lark), evening (owl), or intermediate (neutral) chronotypes. Individuals with morning chronotype wake up and go to bed early. Therefore, their calorie distribution as well as peak mental and physical performances predominantly occur earlier in the day. This is in contrast with individuals with evening chronotype that wake up and go to bed late, resulting in most of their calorie consumption happens later in the day. They are also more active and alert in the evening. Growing evidence has shown that late afternoon or evening exercise is better than morning exercise for blood glucose control in individuals with type 2 diabetes (T2D) or those at risk of T2D. In men with T2D, two weeks of high-intensity interval training (HIIT) reduced continuous glucose monitor (CGM)-based glucose concentration when performed in the afternoon than in the morning. This finding was further supported by a retrospective study involving men at risk for or T2D that found afternoon exercise led to superior peripheral insulin sensitivity, insulin-mediated suppression of adipose tissue lipolysis, and fasting plasma glucose. Interestingly, in a recently published crossover trial involving men and women, with and without T2D, no difference was observed in 24-hour glucose profile assessed using CGM across all cohorts (including gender and diabetes status) between morning and evening exercise. However, morning exercise increased post-exercise blood glucose levels during the two hours recovery period in both men and women with T2D, which was not observed following the evening exercise. It is important to note that all the above-mentioned studies are either excluding individuals with extreme chronotype or the chronotype of the participants was not clearly reported. This limitation raises an important research question: Do people living with extreme chronotype respond differently to timed exercise? Therefore, in this study, it is hypothesize that people living with prediabetes and extreme chronotype will gain superior metabolic benefits when the timing of exercise is aligned with their chronotype. To test this, a randomized controlled cross-over study is conducted in which participants are subjected to three conditions that are no-exercise, morning exercise, and evening exercise. The main outcome is insulin sensitivity determined by a 2-step hyperinsulinemic-euglycemic clamp.

Inclusion criteria

• Able to provide signed and dated written informed consent prior to any study specific procedures
• Adult men and women aged between more than 18 and ≤ 75 years
• Body mass index (BMI) of 25 - 35 kg/m2
• Stable weight (no weight loss or gain > 3 kg in the past 3 months)
• Pre-diabetes defined as an isolated impaired glucose tolerance or a combination of impaired glucose tolerance and impaired fasting glucose (values are based on the American Diabetes Association (ADA):

• impaired glucose tolerance (plasma glucose 140 mg/dL to 199 mg/dL, 120 minutes after consumption of 75g of glucose)
• impaired fasting glucose (fasting plasma glucose 100 mg/dL to 125 mg/dL)
• Morning (Morningness-Eveningness Questionnaire [MEQ] score ≥ 59) or evening (MEQ score ≤ 41) chronotype

Exclusion criteria

• Previously diagnosed with type 2 diabetes
• Moderate to severe anemia (hemoglobin < 10 g/L)
• Uncontrolled hypertension
• Abnormal electrocardiogram (ECG) at rest judged by the study physician
• Pregnancy or breastfeeding
• HIV, hepatitis B, or C infection
• Disorders of blood clotting or wound healing
• Positive history of venous thrombosis (contraindication for clamp)
• Hypersensitivity to local anesthetics (contraindication for fat/muscle biopsies)
• Night shift work in the last 3 months
• Travel across > 1 time zone in the last 3 months
• Participation in another clinical trials that may possibly hamper the study results
• Engagement in structured exercise activities > 2 hours a week
• Any acute condition, exacerbation of chronic condition, or medical history that in the investigator's opinion would interfere with the study
• Any contraindication for MRI scanning
• Medication use known to hamper safety during the study procedures
• Non-German speaking