Acute Timed Exercise and 24h Metabolism

The primary objective of this randomized controlled cross-over study is to investigate if an acute, glycogen lowering exercise bout performed either in the morning or late afternoon differentially affects the respiratory exchange ratio at night in men and women with prediabetes. For this purpose, participants will stay in a respiration chamber and will be subjected to either an exercise bout in the morning or late afternoon.

Appropriate timing of lifestyle interventions may facilitate healthy rhythmicity in metabolism and optimize the effectiveness of such interventions in improving metabolic health. In this context, exercise is well-known to improve (skeletal muscle) energy metabolism and is an established intervention to improve muscle insulin sensitivity and to counter the development of type 2 diabetes (T2D). In addition, exercise may also have beneficial effects on the immune response that is known to impact on insulin sensitivity and overall metabolic health. In this study it is hypothesized that exercise performed at different times of the day exerts a differential effect on 24h metabolism in people at risk for developing T2D. To test this, a randomized controlled cross-over study is conducted in which participants are subjected to either an exercise in the morning or late afternoon while staying in the respiration chamber. Main outcome is substrate utilization during the night as measured with the respiration chamber, but 24-hrs blood draws will also be performed to examine effect of exercise on circulating metabolites.

Eligibility Criteria:
Inclusion Criteria:

* Signed informed consent
* Healthy (determined by dependent physician)
* Man or post-menopausal woman
* Age between 50 - 75 years
* BMI ≥ 25 kg/m2
* Pre-diabetes based on meeting at least one of the following criteria: impaired glucose tolerance defined as plasma glucose values ≥ 7.8 mmol/l and ≤ 11.1 mmol/l 120 minutes after glucose drink consumption during oral glucose tolerance test in screening, impaired fasting glucose defined as fasting plasma glucose ≥ 6.1 mmol/l and ≤ 6.9 mmol/l, insulin resistance defined as a glucose clearance rate ≤ 360 mL/kg/min as determined using OGIS120, HbA1c of 5.7-6.4%
* Regular sleeping habits (7 - 9h of daily sleep)
* Stable diet and weight: No weight gain or loss \> 3kg in the last three months

Exclusion Criteria:

* Not meeting all inclusion criteria
* Fasting plasma glucose
* ≥ 7.0 mmol/L
* Hemoglobin \< 7.8 mmol/L
* Previously diagnosed with type 2 diabetes
* Uncontrolled hypertension
* In case of an abnormal electrocardiogram at rest: this will be discussed with the responsible medical doctor
* Subjects who do not want to be informed about unexpected medical findings during the screening /study, or do not wish that their physician is informed
* Any contra-indication to the Equivital telemetric pill
* Hypomotility disorders of the gastro-intestinal tract
* Extreme early bird or extreme night person (score ≤30 or ≥70 on morning-eveningness questionnaire self assessment)
* Heavily varying sleep-wake rhythm
* Night shift work during last 3 months
* Travel across \> 1 time zone in the last 3 months
* Frequent engagement in programmed exercise as judged by the investigator
* Significant food allergies/intolerance (seriously hampering study meals)
* Participation in another biomedical study within 1 month before the first study visit
* Using \> 400mg caffeine daily (more than 4 cups of coffee or energy drinks)
* Smoking
* Any acute condition, exacerbation of chronic condition, or medical history that would in the investigator's opinion interfere with the study
* Antecubital veins that present tremendous difficulty in obtaining frequent blood draws (e.g. too small)