Clinical ScienceTargeting specific interstitial glycemic parameters with high-intensity interval exercise and fasted-state exercise in type 2 diabetes
Introduction
Elevated blood glucose, including postprandial and fasting hyperglycemia [1], as well as labile glycemic concentrations [2], has been identified as an independent risk factor for the development of diabetic complications. There have been several meta-analyses demonstrating that, on average, exercise has a clinically meaningful impact on glycemic control as measured by glycated hemoglobin (HbA1c) in individuals with type 2 diabetes (T2D) [3], [4]. However, it is less clear whether exercise can be tailored to favor preferential reductions in specific glycemic parameters.
A recent systematic review investigating the effects of exercise on interstitial glycemic parameters measured by continuous glucose monitoring (CGM) showed that aerobic exercise typically lowers postprandial but not fasting glucose [5]. Postprandial hyperglycemia is considered to be more strongly associated with insulin resistance at the level of skeletal muscles, whereas fasting glycemia reflects hepatic insulin resistance [6]. Thus, it is possible that some types of exercise improve muscular insulin sensitivity but have little effects on the hepatic insulin sensitivity. Additionally, it is also possible that the negligible effect of exercise on circulating fasting glucose concentrations is due to a short-lasting effect of traditionally used exercise interventions because circulating fasting glucose concentration is often measured on the day subsequent to exercise.
Modification to exercise interventions in order to favor different effects on muscle versus liver glycogen could have different effects on various glucose parameters. Two such strategies may be high-intensity and fasted-state exercise. An increasingly appreciated approach to increase exercise intensity in T2D is high-intensity interval exercise (HIIE) [7], [8], [9], [10], [11], which involves alternating between repetitions of high-intensity exercise bouts (≥ 70% of maximum or peak oxygen consumption [12], or 80%–100% of maximal heart rate [13], [14]) and lower-intensity recovery periods. Brief bouts of high intensity exercise facilitate muscular glycogenolysis and may stimulate translocation of glucose transporters to a greater degree than lower intensity continuous exercise does [14], [15]. Consequently, glucose uptake during exercise, as well as post-exercise insulin sensitivity, is expected to differ between HIIE and moderate-intensity continuous exercise (MICE; typically defined as 40%–60% of maximum or peak oxygen consumption) [16]. In addition, a previous study has shown that HIIE suppresses hepatic glucose production and thereby fasting blood glucose of individuals with T2D [17].
Glycemic responses to exercise may also be manipulated by altering carbohydrate availability. Although performed predominantly on non-diabetic individuals, pre-prandial exercise resulted in more sustained reduction of blood glucose concentration compared to postprandial exercise, presumably because of greater depletion of hepatic glycogen stores [18]. Therefore, the effects of fasted-state exercise on glycemic parameters may differ from those of post-meal exercise.
To date, no study has simultaneously investigated the effects of HIIE and energy-matched MICE, and the effects of fasted-state and postprandial exercise on glycemic parameters. The primary purpose of the study was to compare the effects of HIIE and MICE, as well as fasted-state and post-breakfast exercise, on daily mean, postprandial and fasting interstitial glycemia. A secondary purpose was to contrast the aforementioned glycemic responses following each of the four exercise conditions (fasted-state HIIE and MICE, and post-breakfast HIIE and MICE) with a sedentary, control condition. We hypothesized that HIIE and fasted-state exercise would improve interstitial fasting and postprandial glycemia to greater degrees than MICE and post-breakfast exercise, respectively. We also hypothesized that the combination of HIIE and fasted-state would improve both fasting and postprandial glycemia.
Section snippets
Research Design
A randomized controlled crossover research design was used. Each participant was studied under five separate experimental conditions: fasted-state HIIE (HIIEfast), post-breakfast HIIE (HIIEfed), fasted-state MICE (MICEfast), post-breakfast MICE (MICEfed), and no exercise (control), in random order separated by 48 h. The randomization of the condition order was performed separately for each participant with no additional methods, such as counterbalancing, to control the order. Forty-eight hours
Participants
Eight males and two females participated in the study (Table 1). One participant only completed three testing conditions due to injury not related to the study. Of the ten participants, five were treated with metformin alone. The others were treated with metformin + sitagliptin, metformin + glyburide, metformin/sitagliptin + gliclazide, metformin + gliclazide, or metformin + saxagliptin + glyclazide.
Laboratory Measures
Fasting capillary blood glucose, HR, RER and V.O2 measured upon arrival at the laboratory did not differ
Discussion
The major findings of this study are that: 1) fasted-state exercise reduced total postprandial interstitial glycemic increment more than post-breakfast exercise did; 2) HIIE decreased nocturnal and fasting glycemia to a greater extent than energy-matched MICE did; and 3) compared to a non-exercise day, HIIEfast improved most aspects of interstitial glycemic parameters (i.e., 24-h mean, MAGE, t> 10.0 mmol·l− 1, postprandial and fasting glucose). Thus, our hypotheses were supported by these
Conclusion
In conclusion, our results show that it is possible to tailor exercise intervention to target specific aspects of interstitial glycemia. High-intensity interval exercise may be incorporated to reduce nocturnal and fasting glucose, while fasted-state exercise can be used to target subsequent postprandial glucose excursions. Given that deteriorated fasting glucose and postprandial glucose contribute differently to the overall hyperglycemia [45] tailoring exercise interventions to target specific
Author Contributions
T.T. designed the study, collected the data, analyzed the data, and wrote the manuscript. B.J.W. screened participants and critically reviewed and revised the manuscript. N.K. and E.M-C. collected data and critically reviewed and revised the manuscript. G.J.B. and L.J.M. designed the study, contributed to discussion and critically reviewed and revised the manuscript. N.B.G. designed the study and wrote the manuscript. T.T. is the guarantor of the study and has full access to all the data in the
Funding
Funding for this study was provided by University of Alberta Faculty of Physical Education & Recreation Human Performance Scholarship Fund.
Conflict of Interest
None.
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