Inflammatory markers and blood glucose are higher after morning vs afternoon exercise in type 2 diabetes

Abstract

Aims/hypothesis: The aim of this study was to investigate effects of time of day on glucose management in individuals with type 2 diabetes undertaking high-intensity interval exercise. Additionally, the association between regular eating behaviour and mean amplitude of glycaemic excursions was examined. Specifically, the primary outcome was to determine the effect of the intervention on 24 h glucose levels.

Methods: A crossover trial was conducted, comprising 12 men and 12 women with type 2 diabetes and 12 men and 12 women without diabetes. Participants performed high-intensity interval exercise sessions in the morning (09:00 hours) or afternoon (16:00 hours) on separate days at least 7 days apart. Standardised meals were provided the day before exercise, on the day of exercise and on the day after exercise. Continuous glucose monitoring was used to estimate blood glucose levels.

Results: The 24 h glucose profile did not differ between morning and afternoon exercise across cohorts. However, morning exercise increased blood glucose during the 2 h post-exercise period in men (p<0.05) and women (p<0.01) with type 2 diabetes, but blood glucose was unaltered following afternoon exercise. Glycaemic variability (assessed using the mean amplitude of glycaemic excursions) was reduced during the 3 day meal intervention in men (p<0.001) and women (p<0.05) with type 2 diabetes, but not in individuals without diabetes. Participants exhibited higher morning cortisol levels (p<0.001) compared with afternoon cortisol levels, independently of diagnosis. Individuals with type 2 diabetes exhibited higher levels of the inflammation marker C-reactive protein (p<0.001) and the heart failure marker NT-proBNP (p<0.001) in the morning than in the afternoon.

Conclusions/interpretation: In type 2 diabetes, afternoon high-intensity interval exercise appears to be more effective than morning high-intensity interval exercise for maintaining glucose management. Further research is needed to explore how elevated morning cortisol levels and inflammatory markers influence the exercise response and affect glucose regulation. Additionally, consistent meal timing and controlled energy intake are recommended for reducing the mean amplitude of glycaemic excursions.

Trial registration: ClinicalTrials.gov NCT05115682.

Keywords: Circadian biology; Continuous glucose monitoring; Diet; High-intensity interval exercise; Inflammation; Sex differences; Type 2 diabetes.

Fig. 1

Elevated blood glucose after morning exercise in individuals with type 2 diabetes (T2D). (a, c) Glucose levels (means ± SEM) were normalised to the exercise start as described in the Methods, and are presented for the 120 min period following the start of exercise for day 1 (pre-exercise day, grey open circles), day 2 (exercise, blue squares) and day 3 (post-exercise day, grey closed circles). (b, d) The AUC was calculated as described in the Methods and is displayed as box-and-whisker plots. Box and whisker plots present the median, first quartile (Q1), and third quartile (Q3). The whiskers extend to the largest and smallest values within 1.5 times the interquartile range (IQR) from the quartiles. Outliers are defined as data points that lie beyond 1.5 times the IQR above Q3 or below Q1. The results of statistical analyses comprise p values derived from the ANOVA (as shown) and post hoc comparisons of exercise responses performed using a linear mixed-effects model as outlined in the Methods: *p<0.05

Fig. 2

Consistent meal timing improves glycaemic variability in individuals with type 2 diabetes (T2D). (a) 24 h glucose concentrations. Control values (black) are the mean of the pre- and post-intervention days. Intervention values (blue) are the mean of the three food control days. White areas are daytime, grey areas are night-time. (b) Glucose AUC calculated for 24 h periods for the pre-intervention day, days 1, 2 and 3, and the post-intervention day. (c) MAGE calculated for 24 h periods for the pre-intervention day, days 1, 2 and 3, and the post-intervention day. For (b) and (c), grey bars signify days during which food was not controlled, coloured bars signify days during which food was controlled. The results are shown as box-and-whisker plots, with dots and lines representing the responses of individual participants. Box and whisker plots present the median, first quartile (Q1), and third quartile (Q3). The whiskers extend to the largest and smallest values within 1.5 times the interquartile range (IQR) from the quartiles. Outliers are defined as data points that lie beyond 1.5 times the IQR above Q3 or below Q1. The results of statistical analyses comprise p values derived from post hoc comparisons to the pre-intervention day following analysis with a linear mixed-effects model and ANOVA as described in the Methods: *p<0.05, **p<0.01, ***p<0.001

Fig. 3

Elevated stress and inflammatory markers in the morning in individuals with type 2 diabetes (T2D). Blood samples were collected immediately before exercise (basal), directly after exercise (post) and at 1 h post-exercise (rest). Values are means ± SEM and are reported for morning (red) vs afternoon (blue) exercise. (a) Cortisol levels; (b) circulating NT-proBNP levels; (c) CRP levels