Timed exercise to acutely improve energy and substrate metabolism at night in men and women with prediabetes

In recent years, several key metabolic processes have proven to be rhythmic
over the course of a day. Furthermore, this rhythmicity in metabolism has been
shown to be disturbed in adults with obesity and related metabolic
disturbances, such as insulin resistance and type 2 diabetes (T2D).
Accordingly, we previously observed a clear 24h rhythmicity in energy and
substrate metabolism in healthy, lean men but a complete lack of such
rhythmicity in insulin-resistant men, at risk for developing T2D. Most
strikingly, fat oxidation increased profoundly during the night in healthy men
whereas individuals with pre-diabetes did not readily switch to the fat
oxidative state during the night.
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 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. Here,
we hypothesize that exercise performed at different times of the day exerts a
differential effect on 24h metabolism in people at risk for developing T2D.

The primary study endpoint is the respiratory exchange ratio (RER) during the
night. The secondary objectives are to examine how differentially timed
exercise affects 1) 24h energy and substrate metabolism and 2) the immune
response based on circulating immune cell phenotypes and 3) continuously
measured blood glucose levels over the 7 days following the exercise bout.

Randomized cross-over design

Exercising in the morning or late afternoon

Low risk