Circadian Misalignment and Insulin Sensitivity

This study will evaluate the effect of circadian misalignment on insulin sensitivity in healthy lean subjects in a randomized cross-over design. Subjects will be admitted to the research facility for two study periods of 3 and 3.5 days. In one of the study periods, the behavioral cycle will be shifted by 12 hours. Insulin sensitivity will be measured with a hyperinsulinemic euglycemic clamp.

Recent evidence shows that misalignment of the circadian rhythm (e.g. by rotating shift work) impairs glucose metabolism markedly, possibly by decreasing insulin sensitivity in peripheral tissues and liver. Nowadays our society is indispensably connected to a lifestyle that allows wakefulness at every time of the 24 hours cycle. Social jetlag is a phenomenon that affects a large part of the general population, thus circadian misalignment extends far beyond those who are on a shift work schedule. Therefore, decreased insulin sensitivity in individuals affected by circadian misalignment may help to explain the increased prevalence of T2DM in night shift workers that has been found in epidemiological studies. The study is an interventional randomized crossover trial in which each subject serves as it owns control. For the study, the investigators ask the subjects to participate in two study periods, one of 3 days length (control condition) and the other of 3.5 days length (misalignment condition). During the 3.5 day misalignment condition, subjects will shift their day-night rhythm by 12 hours, which will lead to maximal circadian misalignment. Insulin sensitivity will be measured by a hyperinsulinemic euglycemic clamp. Secondary parameters will include ex-vivo skeletal muscle mitochondrial function and whole-body energy metabolism.

3.5 days in which the subjects will undergo a maximal circadian misalignment of 12 hours by means of a midday nap during the second day, and a subsequent start of a new normal wake period, shifted 12 hours.

Inclusion Criteria: Caucasian Healthy (as determined by dependent physician based on medical questionnaire) Male Age: 18-35 years Normal BMI (18-25 kg/m2) Regular sleeping time (normally 7 - 9h daily) Habitual bedtime at 11 PM ± 2 hours Exclusion Criteria: Extreme early bird or extreme night person Heavily varying sleep-wake rhythm Shiftwork during last 3 months Travel across >1 time zone in the last 3 months Engagement in exercise > 3 hours total per week Using > 400mg caffeine daily Smoking Unstable body weight (weight gain or loss > 3kg in the last 3 months) Significant food allergies/intolerance (seriously hampering study meals) Participation in another biomedical study within 1 month before the first study visit Claustrophobia Medication use hampering the study (as determined by responsible physician) Recent blood donation. Any contra-indication to the telemetric pill: Any acute condition, exacerbation of chronic condition, or medical history that would in the investigator's opinion interfere with the study