Targeting specific interstitial glycemic parameters with high-intensity interval exercise and fasted-state exercise in type 2 diabetes

    Targeting specific interstitial glycemic parameters with high-intensity interval exercise and fasted-state exercise in type 2 diabetes Tasuku Terada, Ben J. Wilson, Etienne Myette-Cote, Nicholas Kuzik, Gordon J. Bell, Linda J. McCargar, Normand G. Boule PII: DOI: Reference:

S0026-0495(16)00006-8 doi: 10.1016/j.metabol.2016.01.003 YMETA 53362

To appear in:

Metabolism

Received date: Revised date: Accepted date:

25 August 2015 30 December 2015 6 January 2016

Please cite this article as: Terada Tasuku, Wilson Ben J., Myette-Cote Etienne, Kuzik Nicholas, Bell Gordon J., McCargar Linda J., Boule Normand G., Targeting specific interstitial glycemic parameters with high-intensity interval exercise and fasted-state exercise in type 2 diabetes, Metabolism (2016), doi: 10.1016/j.metabol.2016.01.003

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ACCEPTED MANUSCRIPT Targeting specific interstitial glycemic parameters with high-intensity interval

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exercise and fasted-state exercise in type 2 diabetes.

Tasuku Teradaa, Ben J Wilsonb, Etienne Myette-Cόtéa, Nicholas Kuzika, Gordon J Bella, Linda J

Faculty of Physical Education & Recreation, University of Alberta, 1-052 Li Ka Shing Center

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McCargarc, Normand G Bouléa

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for Health Research Innovation, Physical Activity and Diabetes Laboratory, Edmonton, Alberta, Canada T6G 2H9

Department of Medicine, Faculty of Medicine, University of Calgary, Foothills Medical Center-

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b

North Tower, 9th Floor 1403-29th Street NW, Calgary, Alberta, Canada T2N 2T9. Department of Agricultural, Food and Nutritional Science, University of Alberta, 2-012D Li Ka

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c

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Shing Center for Health Research Innovation, Edmonton, Alberta, Canada, T6G 2H9

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Corresponding author: Normand G Boulé Faculty of Physical Education & Recreation, 1-052 Li Ka Shing Center for Health Research Innovation, Edmonton , Alberta, Canada T6G 2H9. Tel.: +1 780 492 4695; fax +1 780 492 2364. E-mail address: [email protected]

Running title: Exercise and interstitial glucose

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ACCEPTED MANUSCRIPT ABSTRACT Aims: To compare the acute glycemic responses to a bout of high-intensity interval exercise

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(HIIE) and energy-matched moderate-intensity continuous exercise (MICE) performed under

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fasted and postprandial conditions.

Methods: A randomized, controlled, crossover design was used. Ten individuals with type 2

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diabetes were each tested in five experimental conditions after an overnight fast: 1) fasted-state

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HIIE (HIIEfast); 2) post-breakfast HIIE (HIIEfed); 3) fasted-state MICE (MICEfast); 4) postbreakfast MICE (MICEfed); and 5) no exercise (control). MICE was performed at workload

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corresponding to 55% of V̇O2peak, whereas HIIE was composed of repetitions of three minutes at workload corresponding to 40% followed by one minute at workload corresponding to 100%

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V̇O2peak. Interstitial glucose was monitored by continuous glucose monitoring over 24 hours

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under standardized diet and medication.

Results: Fasted-state exercise attenuated postprandial glycemic increments (p<0.05) to a greater

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extent than post-breakfast exercise did. HIIE reduced nocturnal and fasting glycemia on the day

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following exercise more than MICE did (main effect: both p<0.05). Compared to the control condition, HIIEfast lowered most interstitial glycemic parameters, i.e., 24-hour mean glucose (1.5 mmol·l-1; p<0.05), fasting glucose (-1.0 mmol·l-1; p<0.05), overall postprandial glycemic increment (-257 mmol·360min·l-1; p<0.05), glycemic variability (-1.79 mmol·l-1; p<0.05), and time spent in hyperglycemia (-283 minutes; p<0.05). Conclusion: This study showed that HIIE is more effective than MICE in lowering nocturnal/fasting glycemia. Exercise performed in the fasted state reduces postprandial glycemic increments to a greater extent than post-breakfast exercise does. Performing HIIE under fasted condition may be most advantageous as it lowered most aspects of glycemia.

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ACCEPTED MANUSCRIPT Keywords: high-intensity interval exercise, fasted-state exercise, continuous glucose monitoring,

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postprandial glucose concentration, glycemic variability.

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Abbreviations:

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mmol·l-1 mmol·l-1

V̇ V̇ V̇

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ostprandial hyperglycemia is

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considered to be more strongly associated with insulin resistance at the level of skeletal muscles, whereas fasting glycemia reflects hepatic insulin resistance [6]

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improve muscular insulin sensitivity but have little effects on the hepatic

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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 favour 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) [7-11], which involves alternating between repetitions of high-intensity exercise bouts (≥70% of maximum or

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ACCEPTED MANUSCRIPT 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

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may stimulate translocation of glucose transporters to a greater degree than lower intensity

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continuous exercise does [14,15]. Consequently, glucose uptake during exercise, as well as postexercise insulin sensitivity, are expected to differ between HIIE and moderate-intensity

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continuous exercise (MICE; typically defined as 40-60% of maximum or peak oxygen

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consumption [16]. In addition, previous study has shown that HIIE suppresses hepatic glucose production and thereby fasting blood glucose of individuals with T2D [17].

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Glycemic responses to exercise may also be manipulated by altering carbohydrate availability. Although performed predominantly on non-diabetic individuals, pre-prandial

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exercise resulted in more sustained reduction of blood glucose concentration compared to

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postprandial exercise, presumably because of greater depletion of hepatic glycogen stores [18].

post-meal exercise.

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Therefore, the effects of fasted-state exercise on glycemic parameters may differ from those of

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To date, no study has simultaneously investigated the effects of HIIE and energymatched 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

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ACCEPTED MANUSCRIPT MICE and post-breakfast exercise, respectively. We also hypothesized that the combination of

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HIIE and fasted-state would improve both fasting and postprandial glycemia.

HIIE (HIIEfast),

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post-breakfast HIIE (HIIEfed), fasted-state MICE (MICEfast), post-breakfast MICE (MICEfed)

T2D

·

T2D

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ACCEPTED MANUSCRIPT reported to a laboratory at the University of Alberta to complete the physical activity readiness questionnaire (PAR-Q+) [20], screening and medical

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information forms, and for assessment of baseline blood pressure, height (seca 216, Chino, CA) and weight (Health o meter®, McCook, IL).

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was also measured by a validated [21] point-

of-care instrument (DCA 2000; Siemens Healthcare Diagnostics Inc. Tarrytown, NY).

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On a separate day, participants performed a graded exercise test on a treadmill

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(Freemotion Fitness, Flaman Fitness, Saskatoon, SK) while connected to an electrocardiograph

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(ECG; CardioCardTM System, Nasiff Association, Inc, Brewerton, NY) to confirm the absence of

TrueMax® metabolic measurement system (ParvoMedics, Sandy, UT) and peak

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oxygen consumption (V̇O2peak) was measured. T

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2.4. Exercise protocols:

MICE V̇O2peak

HIIE corresponding to

workload workload corresponding to

V̇O2peak

V̇O2peak

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MICE)

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HIIE

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iPro2 CGM (Medtronic, Northridge, CA)

handheld glucose monitor One Touch Ultra® 2, LifeScan Milpitas, CA. USA). The measured capillary glucose values

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V̇

V̇ Polar HR monitor

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system

TrueMax® metabolic measurement

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HIIE

MICE

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HIIE

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V̇ V̇

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V̇

V̇

V̇

HIIE

MICE

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HIIE

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(Walk4Life Inc, Plainfield IL)

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handheld glucose monitor

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were exported as previously

described [22]. Interstitial glycemic parameters over the

·l

·

·l

·

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·l

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·l

HIIE

MICE

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·l

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·h-1 and 14.0 (3.4) %, 3.9 (0.9)

·h-1 and 3.9 (2.2) %, and 3.6 (1.0)

·h-1 and 0.9 (1.2) %, respectively.

V̇ HIIE

MICE

HIIE

MICE

V̇

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MICE

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HIIE

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HIIE

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MICE

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HIIE

HIIE

MICE

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MICE

·l

HIIE

MICE

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MICE

HIIE

HIIE

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·l

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HIIE

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HIIE

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HIIE

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MICE

HIIE MICE did HIIE ·

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ACCEPTED MANUSCRIPT Our finding that fasted-state exercise lowered postprandial glucose increments to a greater extent than post

exercise did are similar to those of Oberlin et al., who showed

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that exercise performed before breakfast lowered post-lunch and tended to lower post-breakfast

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glycemia compared to non-exercise days [19]. However, our study adds to the current knowledge by showing that fasted-state exercise is more effective in attenuating overall postprandial

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glycemic increment than post-meal exercise is. This is interesting given that, to date, post-meal

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exercise has generally been considered more beneficial for glucose control as it acutely (within a few hours following an exercise bout) blunts meal-induced hyperglycemia [32], a risk factor for

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diabetic complications [1].

It has been shown that limited exogenous carbohydrate availability increases muscle

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glycogen degradation to meet the energy demand of exercise while ample carbohydrate intake

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results in glycogen sparing [33]. Consequently, we speculate that the greater glycogen depletion and enhanced cellular stress during exercise [34] facilitated the transfer of glucose from blood to

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muscle cells in response to subsequent meals. In support of this notion, available evidence in

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non-diabetic individuals indicates that, compared to exercise with glucose supplementation, exercise accentuates muscular glycogenolysis [33] and increases AMPK activity [34], which are known stimulants for improved insulin sensitivity during recovery [35]. Therefore it is possible that a high exogenous carbohydrate availability during exercise hampers favourable changes in glucose that persist hours after exercise. The more persistent effects of fasted-state exercise on attenuating post-meal glycemic increments may also have an important therapeutic implication because it reduced glycemic variability as estimated by MAGE, which

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a greater nocturnal and

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fasting glucose lowering effect than MICE did. This is

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HIIE

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T2D

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HIIE

[

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HIIE

HIIE

HIIE MICE

MICE HIIE

MICE

HIIE ·

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mmol·l-1

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mmol·l-1

HIIE

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[14,15]

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T2D [39]

HIIE

MICE HIIE

MICE V̇

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MICE

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HIIE

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HIIE

MICE

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MICE

HIIE

HIIE

MICE

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ACCEPTED MANUSCRIPT References: [1] Sorkin JD, Muller DC, Fleg JL, Andres R. The relation of fasting and 2-h postchallenge

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plasma glucose concentrations to mortality - data from the Baltimore longitudinal study of aging

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with a critical review of the literature. Diabetes Care. 2005;28:2626-2632.

[2] Brownlee M, Hirsch IB. Glycemic variability: A hemoglobin A(1c)-independent risk factor

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for diabetic complications. JAMA. 2006;295:1707-1708.

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[3] Boule NG, Haddad E, Kenny GP, Wells GA, Sigal RJ. Effects of exercise on glycemic control and body mass in type 2 diabetes mellitus: A meta-analysis of controlled clinical trials.

MA

JAMA. 2001;286:1218-1227.

[4] Umpierre D, Ribeiro PA, Kramer CK, et al. Physical activity advice only or structured

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exercise training and association with HbA1c levels in type 2 diabetes: A systematic review and

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meta-analysis. JAMA. 2011;305:1790-1799. [5] Macleod SF, Terada T, Chahal BS, Boule NG. Exercise lowers postprandial glucose but not

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fasting glucose in type 2 diabetes: A meta-analysis of studies using continuous glucose

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monitoring. Diabetes Metab Res Rev. 2013;29:593-603. [6] Abdul-Ghani M, Jenkinson C, Richardson D, Devjittripathy, Defronzo R. Insulin secretion and insulin action in subjectswith impaired fasting glucose (IFG) and impaired glucose tolerance (IGT). Diabetes. 2006;55:A321-A321. [7]. Gillen JB, Little JP, Punthakee Z, Tarnopolsky MA, Riddell MC, Gibala MJ. Acute highintensity interval exercise reduces the postprandial glucose response and prevalence of hyperglycemia in patients with type 2 diabetes. Diabetes Obes Metab. 2012;14:575-577.

20

ACCEPTED MANUSCRIPT [8] Karstoft K, Winding K, Knudsen SH, et al. The effects of free-living interval-walking training on glycemic control, body composition, and physical fitness in type 2 diabetic patients:

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A randomized, controlled trial. Diabetes Care. 2013;36:228-36.

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[9] Karstoft K, Christensen CS, Pedersen BK, Solomon TP. The acute effects of interval- vs. continuous-walking exercise on glycemic control in subjects with type 2 diabetes: A cross-over,

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controlled study. J Clin Endocrinol Metab [Epub 2014 Jun 6].

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[10] Little JP, Gillen JB, Percival ME, et al. Low-volume high-intensity interval training reduces

Appl Physiol. 2011;111:1554-1560.

MA

hyperglycemia and increases muscle mitochondrial capacity in patients with type 2 diabetes. J

[11] Terada T, Friesen A, Chahal S, Bell J, McCargar L, Boulé N. Feasibility and preliminary

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efficacy of high intensity interval training in type 2 diabetes. Diabetes Res.Clin.Pract.

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2013;99:120-129.

[12] Francois ME, Little JP. Effectiveness and safety of high-intensity interval training in

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patients with type 2 diabetes. Diabetes spectrum: a publication of the American Diabetes

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Association. 2015;28:39-44.

[13] Weston KS, Wisloff U, Coombes JS. High-intensity interval training in patients with lifestyle-induced cardiometabolic disease: A systematic review and meta-analysis. Br J Sports Med. 2014;48(16):1227-U52. [14] Gibala MJ, Gillen JB, Percival ME. Physiological and health-related adaptations to lowvolume interval training: Influences of nutrition and sex. Sports Med. 2014;44:S127-S137. [15] Hawley JA, Gibala MJ. What's new since hippocrates? preventing type 2 diabetes by physical exercise and diet. Diabetologia. 2012;55:535-539.

21

ACCEPTED MANUSCRIPT [16] Gibala MJ, Little JP. Just HIT it! A time-efficient exercise strategy to improve muscle insulin sensitivity. Journal of Physiology. 2010;588:3341-3342.

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[17] Devlin JT, Hirshman M, Horton ED, Horton ES. Enhanced peripheral and splanchnic

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insulin sensitivity in NIDDM men after single bout of exercise. Diabetes. 1987;36:434-439. [18] Borer KT, Wuorinen EC, Lukos JR, Denver JW, Porges SW, Burant CF. Two bouts of

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exercise before meals, but not after meals, lower fasting blood glucose. Med Sci Sports Exerc.

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2009;41:1606-1614.

[19] Oberlin DJ, Mikus CR, Kearney ML, et al. One bout of exercise alters free-living

MA

postprandial glycemia in type 2 diabetes. Med Sci Sports Exerc. 2014;46:232-238. [20] Warburton D, Jamnik V, Bredin S, Gledhill N. The physical activity readiness questionnaire

ED

(PAR-Q+) and electrical phsyical activity readiness medical examination (eRAPmed-X+).

PT

Health & Fitness Journal of Canada. 2011..

[21] Lenters-Westra E, Slingerland RJ. Six of eight hemoglobin A(1c) point-of-care instruments

CE

do not meet the general accepted analytical performance criteria. Clin Chem. 2010;56:44-52.

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[22] Terada T, Loehr S, Guigard E, et al. Test-retest reliability of a continuous glucose monitoring system in individuals with type 2 diabetes. Diabetes Technol Ther. 2014;16:491-498. [23] Welsh JB, Kaufman FR, Lee SW. Accuracy of the sof-sensor glucose sensor with the iPro calibration algorithm. J Diabetes Sci Technol. 2012;6:475-476. [24] Brunner GA, Ellmerer M, Sendlhofer G, et al. Validation of home blood glucose meters with respect to clinical and analytical approaches. Diabetes Care. 1998;21:585-590. [25] Weir JBD. New methods for calculating metabolic rate with special reference to protein metabolism. J Physiol. 1949;109:1-9.

22

ACCEPTED MANUSCRIPT [26] Mifflin M, St Jeor S, Hill L, Scott B, Daugherty S, Koh Y. A new predictive equation for resting energy expenditure in healthy individuals. Am J Clin Nutr. 1990;51:241-247.

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[27] Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Canadian

diabetes in canada. Can J Diabetes. 2013;37:S1-S212.

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diabetes association 2013 clinical practice guidelines for the prevention and management of

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[28] Wolever T. The glycemic index: A physiological classification of dietary carbohydrate.

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Wallingford: Cambridge; 2006.

[29] Service FJ. Mean amplitude of glycemic excursions, a measure of diabetic instability.

MA

Diabetes. 1970;19:644-655.

[30] Littell RC, Stroup WW, Freund RJ. SAS for linear models. Forth edition ed. Cary, North

ED

Carolina, US: SAS Institute Inc. 2002.

PT

[31] Morris SB, DeShon RP. Combining effect size estimates in meta-analysis with repeated measures and independent-groups designs. Psychol Methods. 2002;7:105-125.

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[32] Colberg SR, Zarrabi L, Bennington L, et al. Postprandial walking is better for lowering the

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glycemic effect of dinner than pre-dinner exercise in type 2 diabetic individuals. J Am Med Dir Assoc. 2009;10:394-397. [33] De Bock K, Derave W, Ramaekers M, Richter EA, Hespel P. Fiber type-specific muscle glycogen sparing due to carbohydrate intake before and during exercise. J Appl Physiol. 2007;102:183-188. [34] Akerstrom TCA, Birk JB, Klein DK, et al. Oral glucose ingestion attenuates exerciseinduced activation of 5 '-AMP-activated protein kinase in human skeletal muscle. Biochem Biophys Res Commun. 2006;342:949-955

23

ACCEPTED MANUSCRIPT [35] Richter EA, Derave W, Wojtaszewski JFP. Glucose, exercise and insulin: Emerging concepts. Journal of Physiology. 2001;535:313-322

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[36] Kim H, Shin J, Lee S, et al. A comparative study of the effects of a dipeptidyl peptidase-IV

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inhibitor and sulfonylurea on glucose variability in patients with type 2 diabetes with inadequate glycemic control on metformin. Diabetes Technol Ther 2013;15:810-816.

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[37] Healy GN, Dunstan DW, Shaw JE, Zimmet PZ, Owen N. Beneficial associations of

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physical activity with 2-h but not fasting blood glucose in Australian adults. Diabetes Care. 2006;29:2598-2604.

MA

[38] Kjaer M, Hollenbeck CB, Frey-Hewitt B, Galbo H, Haskell W, Reaven GM. Glucoregulation and hormonal responses to maximal exercise in non-insulin-dependent diabetes.

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J Appl Physiol. 1990;68:2067-2074..

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[39] Mori Y, Taniguchi Y, Matsuura K, Sezaki K, Yokoyama J, Utsunomiya K. Effects of sitagliptin on 24-H glycemic changes in Japanese patients with type 2 diabetes assessed using

CE

continuous glucose monitoring. Diabetes Technol Ther 2011;13:699-703.

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[40] Bond B, Williams CA, Jackman SR, Woodward A, Armstrong N, Barker AR. Accumulating exercise and postprandial health in adolescents. Metabolism 2015;64(9):10681076.

[41] Francois ME, Baldi JC, Manning PJ, et al. 'Exercise snacks' before meals: A novel strategy to improve glycaemic control in individuals with insulin resistance. Diabetologia. 2014;57:14371445. [42] Kang J, Kelley DE, Robertson RJ, et al. Substrate utilization and glucose turnover during exercise of varying intensities in individuals with NIDDM. Med Sci Sports Exerc. 1999;31:82-89.

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ACCEPTED MANUSCRIPT [43] Larsen JJ, Dela F, Madsbad S, Galbo H. The effect of intense exercise on postprandial glucose homeostasis in type II diabetic patients. Diabetologia. 1999;42:1282-1292.

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[44] Kang J, Raines E, Rosenberg J, Ratamess N, Naclerio F, Faigenbaum A. Metabolic

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responses during postprandial exercise. Res Sports Med. 2013;21:240-252. [45] Monnier L, Lapinski H, Colette C. Contributions of fasting and postprandial plasma glucose

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increments to the overall diurnal hyperglycemia of type 2 diabetic patients - variations with

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increasing levels of HbA(1c). Diabetes Care. 2003;26:881-885.

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Figure 1. Schematic presentation of the experimental design during the laboratory visits.

boxes (

) and arrows

represent metabolic cart and capillary glucose measurements, respectively.

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Figure 2. Glycemic responses to Top: HIIE (□) vs. MICE (●) and Bottom: fasted-state exercise (■) vs. post-breakfast exercise (∆). Control (◊) was included in both figures but no comparisons

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were made against the control condition. HIIE and MICE each include both exercise performed before and after breakfast. Similarly, fasted-state and post-breakfast exercise each include both HIIE and MICE. Dots represent means and error bars represent SE. *Significant difference (p<0.05) between HIIE and MICE or between post-breakfast vs. fasted. Shaded area represents meals. Nocturnal glucose was measured between 0:00 and 5:00. Fasting glucose was one-hour average glucose concentration following eight hours of fasting. HIIE= high intensity interval exercise, MICE= moderate intensity continuous exercise.

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ACCEPTED MANUSCRIPT Table 1. Participants’ characteristics

)

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47 - 69 1 – 13 157.0 – 186.0 71.0 – 120.9 21.2 – 39.3 6.0 – 9.4 42.0 – 79.0 17.2 – 36.8

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Range

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% female Age (y) Duration of T2D (y) Height (cm) Weight (kg) BMI (kg·m ) HbA1c (%) HbA1c ( · ) V̇O2peak ( · ·

n=10 20 60 (6) 6.8 (4.6) 172.4 (9.4) 91.4 (17.1) 30.8 (5.4) 7.1 (1.0) 53.9 (10.9) 25.5 (6.6)

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Variable

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Data are mean (SD)

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HbA1c: glycosylated hemoglobin, V̇O2peak: peak oxygen consumption, BMI: body mass index

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ACCEPTED MANUSCRIPT Table 2. Metabolic and glycemic responses upon arriving at the laboratory and during exercise P-value

Pre-test

RER

8.5 (2.0) 2.9 (0.2) 0.86 (0.08)

%V̇O2peak

0.473 (0.17) 0.708 (0.10) 0.271 (0.21)

0.432 (0.08) 0.984 (0.26) 0.219 (0.38)

55.1 (3.6) 14.3 (1.0) 0.89 (0.05)

53.2 (4.8) 13.5 (1.1) 0.82 (0.04)

54.6 (5.6) 14.3 (1.3) 0.85 (0.05)

0.317 (0.22) 0.699 (0.10) 0.007 (0.73)

0.259 (0.13) 0.208 (0.67) 0.001 (0.62)

53.5 (5.7)

57.0 (3.3)

54.0 (5.3)

55.1 (4.9)

13.5 (3.4)

15.0 (4.2)

13.7 (3.6)

14.5 (3.9)

0.83 (0.04)

0.88 (0.03)

0.81 (0.04)

0.85 (0.03)

0.518 0.021 (0.12 (0.48 ) ) 0.611 0.024 (0.14 (0.65 ) ) <0.001 <0.001 (0.95) (1.5)

354 (85)

371 (94)

351 (88)

362 (101)

0.410 (0.07)

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RER

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Exercise (50-60th min)

RER

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V̇ O2 (mL·kg-1·min-1)

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%V̇O2peak

MICE

fasted vs. fed

vs.

8.6 (1.4) 3.0 (0.3) 0.85 (0.06)

55.0 (6.3) 13.8 (0.9) 0.86 (0.05)

V̇O2 (mL·kg-1·min-1)

HIIE

8.9 (2.5) 2.9 (0.3) 0.87 (0.06)

Exercise (20-30th min)

8.6 (2.0) 2.9 (0.3) 0.82 (0.04)

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V̇O2 (mL·kg-1·min-1)

8.8 (2.2) 2.8 (0.2) 0.83 (0.04)

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Fasting glucose (mmol·l-1)

MICEfed

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Control HIIEfast HIIEfed MICEfast

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Conditions, mean (SD)

Exercise (0-60th min)

Energy expenditure (kcal)

0.026 (0.09)

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ACCEPTED MANUSCRIPT %V̇ O2peak: percent peak oxygen consumption, V̇ O2: oxygen consumption, RER: respiratory exchange

HIIE

ratio, HIIE

MICE

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MICE

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V̇O2

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No significant interaction observed between exercise type (HIIE vs. MICE)

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and meal status (fasted vs. post-breakfast) for any of the variables. No significant differences were observed between each of the four exercise conditions and control. *Effect sizes are shown in absolute

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values.

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ACCEPTED MANUSCRIPT

HIIE

MICE

MICE

RI P

T

HIIE

†

mmol·l-1

†

NU

mmol·l-1 mmol·l-1

‡ mmol·120 min·l-1

ED

mmol·120 min·l-1

MA

mmol·120 min·l-1

*

mmol·360 min·l-1

PT

mmol·l-1

‡

†

†

†

CE

mmol·l-1

HIIE

AC

HIIE

fasted vs. fed

SC

mmol·L-1 (min)

HIIE vs. MICE

MICE

MICE HIIE MICE HIIE

No significant interaction was observed for any of the variables. ¶Effect sizes are shown in absolute values. †

‡ 31