Aims/hypothesisExercise is recommended for the treatment and prevention of type 2 diabetes. However, the most effective time of day to achieve beneficial effects on health remains unknown. We aimed to determine whether exercise training at two distinct times of day would have differing effects on 24 h blood glucose levels in men with type 2 diabetes.MethodsEleven men with type 2 diabetes underwent a randomised crossover trial. Inclusion criteria were 45–68 years of age and BMI between 23 and 33 kg/m2. Exclusion criteria were insulin treatment and presence of another systemic illness. Researchers were not blinded to the group assignment. The trial involved 2 weeks of either morning or afternoon high-intensity interval training (HIIT) (three sessions/week), followed by a 2 week wash-out period and a subsequent period of the opposite training regimen. Continuous glucose monitor (CGM)-based data were obtained.ResultsMorning HIIT increased CGM-based glucose concentration (6.9 ± 0.4 mmol/l; mean ± SEM for the exercise days during week 1) compared with either the pre-training period (6.4 ± 0.3 mmol/l) or afternoon HIIT (6.2 ± 0.3 mmol/l for the exercise days during week 1). Conversely, afternoon HIIT reduced the CGM-based glucose concentration compared with either the pre-training period or morning HIIT. Afternoon HIIT was associated with elevated thyroid-stimulating hormone (TSH; 1.9 ± 0.2 mU/l) and reduced T4 (15.8 ± 0.7 pmol/l) concentrations compared with pre-training (1.4 ± 0.2 mU/l for TSH; 16.8 ± 0.6 pmol/l for T4). TSH was also elevated after morning HIIT (1.7 ± 0.2 mU/l), whereas T4 concentrations were unaltered.Conclusions/interpretationAfternoon HIIT was more efficacious than morning HIIT at improving blood glucose in men with type 2 diabetes. Strikingly, morning HIIT had an acute, deleterious effect, increasing blood glucose. However, studies of longer training regimens are warranted to establish the persistence of this adverse effect. Our data highlight the importance of optimising the timing of exercise when prescribing it as treatment for type 2 diabetes.

Rat L6, mouse C2C12, and primary human skeletal muscle cells (HSMCs) are commonly used to study biological processes in skeletal muscle, and experimental data on these models are abundant. However, consistently matched experimental data are scarce, and comparisons between the different cell types and adult tissue are problematic. We hypothesized that metabolic differences between these cellular models may be reflected at the mRNA level. Publicly available data sets were used to profile mRNA levels in myotubes and skeletal muscle tissues. L6, C2C12, and HSMC myotubes were assessed for proliferation, glucose uptake, glycogen synthesis, mitochondrial activity, and substrate oxidation, as well as the response to in vitro contraction. Transcriptomic profiling revealed that mRNA of genes coding for actin and myosin was enriched in C2C12, whereas L6 myotubes had the highest levels of genes encoding glucose transporters and the five complexes of the mitochondrial electron transport chain. Consistently, insulin-stimulated glucose uptake and oxidative capacity were greatest in L6 myotubes. Insulin-induced glycogen synthesis was highest in HSMCs, but C2C12 myotubes had higher baseline glucose oxidation. All models responded to electrical pulse stimulation-induced glucose uptake and gene expression but in a slightly different manner. Our analysis reveals a great degree of heterogeneity in the transcriptomic and metabolic profiles of L6, C2C12, or primary human myotubes. Based on these distinct signatures, we provide recommendations for the appropriate use of these models depending on scientific hypotheses and biological relevance.

Exercise elicits high energy demands, stimulating cardiorespiratory function and substrate mobilisation and oxidation. Repeated bouts of exercise lead to whole-body adaptations, which improve athletic performance. Distinct exercise modalities and intensities and nutritional conditions pose specific physiological challenges, subsequently inducing different adaptations to training. Athletes often modify these variables to achieve individualised training goals and maximise performance. Exercise training improves glycaemic control in individuals with type 2 diabetes; however, the precise training regimen that confers the most beneficial metabolic adaptations in this population is unknown. In this review, we discuss how modifying exercise type, intensity and modality and nutritional status affects the beneficial effects of exercise on glycaemic control in individuals with type 2 diabetes. Evidence indicates that greater improvements in glycaemic control can be achieved through combined aerobic and resistance training regimens compared with either training type alone. However, the increased frequency of training and a greater number of exercise bouts during combined programmes could be responsible for apparent advantages over a single training modality. The beneficial effects of aerobic exercise on glycaemic control seem to rise with training intensity, with superior adaptations achieved by high-intensity interval training (HIT). In addition, training with low carbohydrate availability (‘training low’) improves cardiorespiratory function and skeletal muscle oxidative capacity more than conventional training in healthy untrained individuals. Examinations of various training regimens are warranted to assess the safety, efficacy, feasibility and beneficial effects in the type 2 diabetes population. Just like competitive athletes, individuals with type 2 diabetes should be encouraged to adopt training regimens that improve fitness and metabolism. Graphical abstract Electronic supplementary material The online version of this article (10.1007/s00125-020-05166-9) contains a slideset of the figures for download, which is available to authorised users.

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