Exercise, Chronotype, and Prediabetes

Overview

The goal of this clinical trial is to find out whether exercising at the right time of day, based on a person's natural body clock, leads to greater health benefits in people living with prediabetes. The main question it aims to answer is whether doing a single session of exercise in the morning or in the evening affects how the body handles sugar differently in adults with prediabetes who have an extreme natural body clock. This will be done by comparing three conditions (no-exercise, morning exercise, and evening exercise) within the same participant. Each condition will be tested on a different day, with at least 14 days between the test days. During the no-exercise test days, participants will come to the study centre and will only be allowed to do sedentary activities (e.g. office work, reading, or screen time). During the morning exercise test days, participants will perform an exercise session at 9:00 am that involves short periods of very hard effort followed by short rest periods. Whereas for the evening exercise test days, the same type of exercise will be performed at 5:00 pm.

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.