Afternoon exercise is more efficacious than morning exercise at improving blood glucose levels in individuals with type 2 diabetes: a randomised crossover trial

Exercise is recommended for the prevention and treatment of type 2 diabetes [1]. Low-volume high-intensity interval training (HIIT) remodels skeletal muscle and the cardiorespiratory system to a similar extent as continuous moderate-intensity training, with reduced time commitment and exercise volume [2]. In addition, glucose tolerance, insulin sensitivity and muscle oxidative capacity show circadian oscillations [3, 4]. Interactions between these factors could lead to divergent physiological adaptations to exercise training at different times of day. By determining the effects of morning and afternoon HIIT on 24 h blood glucose in men with type 2 diabetes in ‘free-living’ conditions, we tested the hypothesis that time of day would influence the metabolic response to exercise.

This trial was approved by the regional ethics board at the Karolinska Institutet, Stockholm, Sweden (2016/1421-31/1). All participants gave their informed consent.

Morning HIIT increased CGM-based glucose concentrations on Exercise days during week 1 (6.9 ± 0.4 mmol/l; mean ± SEM) (Fig. 1a) and week 2 (6.6 ± 0.4 mmol/l) (Fig. 1b) compared with either the pre-training days (6.4 ± 0.3 mmol/l) or afternoon HIIT (6.2 ± 0.3 and 6.1 ± 0.4 mmol/l for week 1 and 2, respectively) at several time points. Conversely, afternoon HIIT reduced CGM-based glucose concentration on Exercise days during week 1 (Fig. 1a) and week 2 (Fig. 1b) of training compared with either pre-training or morning HIIT at several time points. Morning HIIT also increased CGM-based glucose concentrations on Rest days during week 2 (Fig. 1d), but not week 1 (Fig. 1c), compared with pre-training days or afternoon HIIT at several time points. Mean 24 h glucose curves for the pre-training period and the last 3 days of the wash-out period were unaltered (data not shown). Thus, the wash-out period was sufficient to remove the effects of HIIT. Afternoon HIIT elevated parathyroid hormone (PTH) and thyroid-stimulating hormone (TSH) concentrations, and reduced T₄ concentration, compared with pre-training concentrations (Table 2). TSH was also elevated after morning HIIT, whereas PTH and T₄ concentrations were unaltered.

To our knowledge, this is the first study performed in a real-life setting that compares the impact of 2 weeks of HIIT at different times of day on blood glucose excursions in people with type 2 diabetes. Afternoon HIIT was more efficacious than morning HIIT in improving blood glucose levels. Unexpectedly, morning HIIT elevated glucose levels at several time points throughout the day compared with the pre-training period and afternoon HIIT. Conversely, afternoon HIIT lowered blood glucose at several time points throughout the day compared with pre-training and morning HIIT. Our results are clinically relevant, showing that timing of exercise affects the glycaemic response to HIIT in men with type 2 diabetes.

The circadian clock is a key homeostatic regulator that is synchronised by photic and non-photic stimuli (food intake, temperature and physical activity), and controls many genomic and physiological responses in virtually all cells [1]. We reasoned that if the timing of exercise could be optimised to coincide with these responses, its potency as a therapeutic tool might be augmented. Several lines of evidence suggest that the timing of exercise alters physiological responses diversely. In healthy young men, parasympathetic and sympathetic activity during the next nocturnal sleep is differentially enhanced by morning and evening exercise, as evidenced by changes in body temperature, heart rate and heart rate variability [5]. Moreover, human skeletal muscular strength and mitochondrial function peak in late afternoon [4, 6], suggesting a circadian rhythm of oxidative metabolism.

Here we report that the time of day affects the blood glucose response to exercise in people with type 2 diabetes, with improvements in daily glucose excursions observed in conjunction with afternoon HIIT. Our results are compatible with a previous report that a session of moderate-intensity exercise performed in the morning vs the afternoon conferred a lower risk of late-onset hypoglycaemia and improved metabolic control on the subsequent day in young individuals with type 1 diabetes [7]. We report that morning HIIT increased CGM-based glucose concentration acutely as well as on the subsequent rest day during week 2 of training. Collectively, these results imply that the timing of exercise impacts blood glucose excursions over the day. Aligning exercise bouts with the systemic circadian rhythm appears to confer a differential glycaemic response in people with diabetes.

Optimising the timing of an exercise session with defined eating patterns may interact with the circadian clock signal to prevent disease pathogenesis [1]. Morning HIIT has been shown to improve blood glucose levels in individuals with type 2 diabetes when performed under controlled conditions with standardised meals provided 1.5 h before the exercise session [8]. In our study, morning HIIT had an acute deleterious effect on blood glucose. Conceivably, individuals participating in an exercise programme in a real-life setting may consume meals closer to or directly after the morning exercise session. Such a scenario, potentiated by the suppressive effects of high-intensity exercise on gastric emptying [9], may partially account for deleterious effects of morning HIIT on blood glucose in our study. Thus, timing is also important in respect to food intake, with a better glycaemic response achieved with postprandial exercise in people with type 2 diabetes [10].

Exercise at different times of day may coincide with fuel utilisation preferences on the part of the working muscles. Moreover, HIIT has a preference for carbohydrate oxidation when compared with moderate-intensity exercise [11]. Thus, differential fuel utilisation patterns during morning vs afternoon exercise may partly explain the changes in blood glucose regulation between trials. Morning HIIT-induced increases in blood glucose levels were predominately observed in week 1. An acute dysregulation of diurnal hormonal rhythms could account for this phenomenon. Supporting this assertion, afternoon HIIT potentiated the TSH and T₄ responses. In week 2 of the morning HIIT, we observed an apparent improvement in glucose levels, as the participants become better acclimated to the training regimen. Studies of longer training periods are thus warranted to establish the persistence of these adverse effects.

We conducted a field-based study in ‘free-living’ individuals, so specific factors responsible for differing blood glucose levels between morning and afternoon HIIT trials remain to be elucidated. Due to the randomised crossover design and paired nature of the data, putative individual differences in the sleep/wake cycle and sleep architecture are mostly accounted for. Future studies are warranted to characterise the underlying hormonal and metabolic changes to exercise training at different times of day in healthy and diseased populations.

Although HIIT is promising for the management of type 2 diabetes, our data indicate that the timing of exercise should be considered. This concern may be modality and population dependent. In light of diverse hormonal responses and fuel utilisation preference [11], less intense forms of exercise may have differing effects on blood glucose and associated metabolic responses. Conversely, individuals prone to nocturnal hypoglycaemia or who are receiving insulin treatment might respond differently to the same training regimen. In conclusion, our data highlight the importance of optimising the timing of exercise sessions to improve glycaemic control in people with type 2 diabetes.