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      Effects of High-Intensity Interval Exercise versus Moderate Continuous Exercise on Glucose Homeostasis and Hormone Response in Patients with Type 1 Diabetes Mellitus Using Novel Ultra-Long-Acting Insulin

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          Abstract

          Introduction

          We investigated blood glucose (BG) and hormone response to aerobic high-intensity interval exercise (HIIE) and moderate continuous exercise (CON) matched for mean load and duration in type 1 diabetes mellitus (T1DM).

          Material and Methods

          Seven trained male subjects with T1DM performed a maximal incremental exercise test and HIIE and CON at 3 different mean intensities below (A) and above (B) the first lactate turn point and below the second lactate turn point (C) on a cycle ergometer. Subjects were adjusted to ultra-long-acting insulin Degludec (Tresiba/ Novo Nordisk, Denmark). Before exercise, standardized meals were administered, and short-acting insulin dose was reduced by 25% (A), 50% (B), and 75% (C) dependent on mean exercise intensity. During exercise, BG, adrenaline, noradrenaline, dopamine, cortisol, glucagon, and insulin-like growth factor-1, blood lactate, heart rate, and gas exchange variables were measured. For 24 h after exercise, interstitial glucose was measured by continuous glucose monitoring system.

          Results

          BG decrease during HIIE was significantly smaller for B (p = 0.024) and tended to be smaller for A and C compared to CON. No differences were found for post-exercise interstitial glucose, acute hormone response, and carbohydrate utilization between HIIE and CON for A, B, and C. In HIIE, blood lactate for A (p = 0.006) and B (p = 0.004) and respiratory exchange ratio for A (p = 0.003) and B (p = 0.003) were significantly higher compared to CON but not for C.

          Conclusion

          Hypoglycemia did not occur during or after HIIE and CON when using ultra-long-acting insulin and applying our methodological approach for exercise prescription. HIIE led to a smaller BG decrease compared to CON, although both exercises modes were matched for mean load and duration, even despite markedly higher peak workloads applied in HIIE. Therefore, HIIE and CON could be safely performed in T1DM.

          Trial Registration

          ClinicalTrials.gov NCT02075567 http://www.clinicaltrials.gov/ct2/show/NCT02075567

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          Most cited references19

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          Aerobic high-intensity intervals improve VO2max more than moderate training.

          The present study compared the effects of aerobic endurance training at different intensities and with different methods matched for total work and frequency. Responses in maximal oxygen uptake (VO2max), stroke volume of the heart (SV), blood volume, lactate threshold (LT), and running economy (CR) were examined. Forty healthy, nonsmoking, moderately trained male subjects were randomly assigned to one of four groups:1) long slow distance (70% maximal heart rate; HRmax); 2)lactate threshold (85% HRmax); 3) 15/15 interval running (15 s of running at 90-95% HRmax followed by 15 s of active resting at 70% HRmax); and 4) 4 x 4 min of interval running (4 min of running at 90-95% HRmax followed by 3 min of active resting at 70%HRmax). All four training protocols resulted in similar total oxygen consumption and were performed 3 d.wk for 8 wk. High-intensity aerobic interval training resulted in significantly increased VO2max compared with long slow distance and lactate-threshold training intensities (P<0.01). The percentage increases for the 15/15 and 4 x 4 min groups were 5.5 and 7.2%, respectively, reflecting increases in V O2max from 60.5 to 64.4 mL x kg(-1) x min(-1) and 55.5 to 60.4 mL x kg(-1) x min(-1). SV increased significantly by approximately 10% after interval training (P<0.05). : High-aerobic intensity endurance interval training is significantly more effective than performing the same total work at either lactate threshold or at 70% HRmax, in improving VO2max. The changes in VO2max correspond with changes in SV, indicating a close link between the two.
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            Cell-cell and intracellular lactate shuttles.

            Once thought to be the consequence of oxygen lack in contracting skeletal muscle, the glycolytic product lactate is formed and utilized continuously in diverse cells under fully aerobic conditions. 'Cell-cell' and 'intracellular lactate shuttle' concepts describe the roles of lactate in delivery of oxidative and gluconeogenic substrates as well as in cell signalling. Examples of the cell-cell shuttles include lactate exchanges between between white-glycolytic and red-oxidative fibres within a working muscle bed, and between working skeletal muscle and heart, brain, liver and kidneys. Examples of intracellular lactate shuttles include lactate uptake by mitochondria and pyruvate for lactate exchange in peroxisomes. Lactate for pyruvate exchanges affect cell redox state, and by itself lactate is a ROS generator. In vivo, lactate is a preferred substrate and high blood lactate levels down-regulate the use of glucose and free fatty acids (FFA). As well, lactate binding may affect metabolic regulation, for instance binding to G-protein receptors in adipocytes inhibiting lipolysis, and thus decreasing plasma FFA availability. In vitro lactate accumulation upregulates expression of MCT1 and genes coding for other components of the mitochondrial reticulum in skeletal muscle. The mitochondrial reticulum in muscle and mitochondrial networks in other aerobic tissues function to establish concentration and proton gradients necessary for cells with high mitochondrial densities to oxidize lactate. The presence of lactate shuttles gives rise to the realization that glycolytic and oxidative pathways should be viewed as linked, as opposed to alternative, processes, because lactate, the product of one pathway, is the substrate for the other.
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              What are the health benefits of physical activity in type 1 diabetes mellitus? A literature review.

              Physical activity improves well-being and reduces the risk of heart disease, cancer and type 2 diabetes mellitus in the general population. In individuals with established type 2 diabetes, physical activity improves glucose and lipid levels, reduces weight and improves insulin resistance. In type 1 diabetes mellitus, however, the benefits of physical activity are less clear. There is poor evidence for a beneficial effect of physical activity on glycaemic control and microvascular complications, and significant risk of harm through hypoglycaemia. Here we review the literature relating to physical activity and health in type 1 diabetes. We examine its effect on a number of outcomes, including glycaemic control, lipids, blood pressure, diabetic complications, well-being and overall mortality. We conclude that whilst there is sufficient evidence to recommend physical activity in the management of type 1 diabetes, it is still unclear as to what form, duration and intensity should be recommended and whether there is benefit for many of the outcomes examined.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                28 August 2015
                2015
                : 10
                : 8
                : e0136489
                Affiliations
                [1 ]Department of Internal Medicine, Division of Endocrinology & Metabolism, Medical University of Graz, Graz, Austria
                [2 ]Institute of Sports Sciences, Exercise Physiology & Training Research Group, University of Graz, Graz, Austria
                [3 ]Center of Sports Medicine & Sports Orthopedics, University Outpatient Clinic, University of Potsdam, Potsdam, Germany
                University of Milan, ITALY
                Author notes

                Competing Interests: No conflict of interest: Othmar Moser, Gerhard Tschakert, Alexander Mueller, Werner Groeschl, Barbara Obermayer-Pietsch and Peter Hofmann. Duality of interests: Gerd Koehler has received lecture fees from Novo Nordisk, AstraZeneca, Bristol-Myers Squibb, Roche Diagnostics, Novartis, MSD and Eli Lilly. Thomas R. Pieber has participated in advisory panels and acted as a consultant for Novo Nordisk. This does not alter the authors' adherence to PLOS ONE policies on sharing data and material.

                Conceived and designed the experiments: OM GT AM TRP BO GK PH. Performed the experiments: OM GT AM WG GK PH. Analyzed the data: OM GT PH. Contributed reagents/materials/analysis tools: OM AM BO. Wrote the paper: OM GT PH.

                Article
                PONE-D-15-09641
                10.1371/journal.pone.0136489
                4552855
                26317981
                87fa0d80-0608-4677-b80e-c3e6496c3aac
                Copyright @ 2015

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                : 10 March 2015
                : 30 July 2015
                Page count
                Figures: 9, Tables: 3, Pages: 17
                Funding
                The authors have no support or funding to report.
                Categories
                Research Article
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

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