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      Heart rate dynamics during cardio-pulmonary exercise testing are associated with glycemic control in individuals with type 1 diabetes

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          Abstract

          Introduction

          This study investigated the degree and direction (k HR) of the heart rate to performance curve (HRPC) during cardio-pulmonary exercise (CPX) testing and explored the relationship with diabetes markers, anthropometry and exercise physiological markers in type 1 diabetes (T1DM).

          Material and methods

          Sixty-four people with T1DM (13 females; age: 34 ± 8 years; HbA 1c: 7.8 ± 1% (62 ± 13 mmol.mol -1) performed a CPX test until maximum exhaustion. k HR was calculated by a second-degree polynomial representation between post-warm up and maximum power output. Adjusted stepwise linear regression analysis was performed to investigate k HR and its associations. Receiver operating characteristic (ROC) curve was performed based on k HR for groups k HR < 0.20 vs. > 0.20 in relation to HbA 1c.

          Results

          We found significant relationships between k HR and HbA 1c ( β = -0. 70, P < 0. 0001), age ( β = -0. 23, P = 0. 03) and duration of diabetes ( β = 0. 20, P = 0. 04). Stepwise linear regression resulted in an overall adjusted R 2 of 0.57 ( R = 0. 79, P < 0. 0001). Our data revealed also significant associations between k HR and percentage of heart rate at heart rate turn point from maximum heart rate ( β = 0. 43, P < 0. 0001) and maximum power output relativized to bodyweight ( β = 0. 44, P = 0. 001) (overall adjusted R 2 of 0.44 ( R = 0. 53, P < 0. 0001)). ROC curve analysis based on k HR resulted in a HbA 1c threshold of 7.9% (62 mmol.mol -1).

          Conclusion

          Our data demonstrate atypical HRPC during CPX testing that were mainly related to glycemic control in people with T1DM.

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          Most cited references29

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          Glycaemic control of Type 1 diabetes in clinical practice early in the 21st century: an international comparison.

          Improving glycaemic control in people with Type 1 diabetes is known to reduce complications. Our aim was to compare glycaemic control among people with Type 1 diabetes using data gathered in regional or national registries.
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            Insulin resistance in adolescents with type 1 diabetes and its relationship to cardiovascular function.

            Cardiovascular disease is the major cause of death in adults with diabetes, yet little is specifically known about the effects of type 1 diabetes (T1D) on cardiovascular outcomes in youth. Although insulin resistance (IR) likely contributes to exercise and cardiovascular dysfunction in T2D, IR is not typically considered a contributor in T1D. We hypothesized that cardiopulmonary fitness would be reduced in T1D youth in association with IR and cardiovascular dysfunction. This cross-sectional study at an academic hospital included 12 T1D adolescents compared with 12 nondiabetic controls, similar in age, pubertal stage, activity level, and body mass index. Cardiopulmonary fitness was measured by peak oxygen consumption (VO(2)peak) and oxygen uptake kinetics (VO(2)kinetics), IR by hyperinsulinemic clamp, cardiac function by echocardiography, vascular function by venous occlusion plethysmography, intramyocellular lipid by magnetic resonance spectroscopy, and body composition by dual-energy x-ray absorptiometry. T1D adolescents had significantly decreased VO(2)peak, peak work rate, and insulin sensitivity compared with nondiabetic adolescents. T1D youth also had reduced vascular reactivity and evidence of diastolic dysfunction and left ventricular hypertrophy. Despite their IR and reduced cardiovascular fitness, T1D youth had paradoxically normal intramyocellular lipid, waist to hip ratio, and serum lipids and high adiponectin levels. In multivariate analysis, IR primarily, and forearm blood flow secondarily, independently predicted VO(2)peak. T1D youth demonstrated IR, impaired functional exercise capacity and cardiovascular dysfunction. The phenotype of IR in T1D youth was unique, suggesting a pathophysiology that is different from T2D, yet may adversely affect long-term cardiovascular outcomes.
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              Association Between Physical Activity and Risk of All-Cause Mortality and Cardiovascular Disease in Patients With Diabetes

              OBJECTIVE The association between habitual physical activity (PA) and lowered risk of all-cause mortality (ACM) and cardiovascular disease (CVD) has been suggested in patients with diabetes. This meta-analysis summarizes the risk reduction in relation to PA, focusing on clarifying dose-response associations. RESEARCH DESIGN AND METHODS Electronic literature searches were conducted for cohort studies that examined relative risk (RR) of ACM or CVD in relation to PA in patients with diabetes. For the qualitative assessment, RR for the highest versus the lowest PA category in each study was pooled with a random-effects model. We added linear and spline regression analyses to assess the quantitative relationship between increases in PA and ACM and CVD risk. RESULTS There were 17 eligible studies. Qualitatively, the highest PA category had a lower RR [95% CI] for ACM (0.61 [0.52–0.70]) and CVD (0.71 [0.60–0.84]) than the lowest PA category. The linear regression model indicated a high goodness of fit for the risk of ACM (adjusted R 2 = 0.44, P = 0.001) and CVD (adjusted R 2 = 0.51, P = 0.001), with the result that a 1 MET-h/day incrementally higher PA was associated with 9.5% (5.0–13.8%) and 7.9% (4.3–11.4%) reductions in ACM and CVD risk, respectively. The spline regression model was not significantly different from the linear model in goodness of fit (P = 0.14 for ACM risk; P = 0.60 for CVD risk). CONCLUSIONS More PA was associated with a larger reduction in future ACM and CVD risk in patients with diabetes. Nevertheless, any amount of habitual PA was better than inactivity.
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                Author and article information

                Contributors
                Role: InvestigationRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: SoftwareRole: Writing – review & editing
                Role: ValidationRole: Writing – review & editing
                Role: Writing – review & editing
                Role: MethodologyRole: Writing – review & editing
                Role: Formal analysisRole: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: Data curationRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: Data curationRole: Funding acquisitionRole: InvestigationRole: Methodology
                Role: InvestigationRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                2 April 2018
                2018
                : 13
                : 4
                : e0194750
                Affiliations
                [1 ] Diabetes Research Group, Medical School, Swansea University, Swansea, United Kingdom
                [2 ] Applied Sport, Technology, Exercise and Medicine Research Centre (A-STEM), College of Engineering, Swansea University, Swansea, United Kingdom
                [3 ] Novo Nordisk A/S, Søborg, Denmark
                [4 ] Profil, Neuss, Germany
                University of Colorado Denver School of Medicine, UNITED STATES
                Author notes

                Competing Interests: O. Moser has received lecture fees from Medtronic, a travel grant from Novo Nordisk A/S and research grants from Sêr Cymru II COFUND fellowship/European Union and Novo Nordisk A/S. M. L. Eckstein has received a KESS2/European Social Fund scholarship. S. C. Bain reports having received honoraria, teaching and research grants from the Abbott, Astra Zeneca, Boehringer Ingelheim, BMS, Diartis, Eli Lily and Company, GlaxoSmithKline, Johnson & Johnson, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, Roche, Sanofi-Aventis, Schering-Plough, Servier and Takeda. T. Heise reports having received research funds from Adocia, Astra Zeneca, BD, Biocon, Boehringer Ingelheim, Dance Pharmaceuticals, Grünenthal, Eli Lily and Company, Medtronic, Novo Nordisk, Novartis, Sanofi and Senseonics and having received speaker honoraria and travel grants from Eli Lily and Company, Mylan and Novo Nordisk. R. M. Bracken reports having received honoraria, travel and educational grant support from, Boehringer-Ingelheim, Eli Lily and Company, Novo Nordisk, Sanofi-Aventis. E. Zijlstra, R. Deere and O. McCarthy have no disclosures to report. H. L. Haahr is employee and shareholder in Novo Nordisk A/S.

                Author information
                http://orcid.org/0000-0002-1661-0685
                Article
                PONE-D-17-32452
                10.1371/journal.pone.0194750
                5880363
                29608593
                29ffb87c-9cf1-454e-8bef-c51c99f1e518
                © 2018 Moser et al

                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
                : 26 September 2017
                : 7 March 2018
                Page count
                Figures: 5, Tables: 1, Pages: 11
                Funding
                Funded by: Novo Nordisk A/S
                Award ID: NN1250-3999
                Award Recipient :
                This study was supported by Novo Nordisk A/S (NN1250-3999 to Tim Heise).
                Categories
                Research Article
                Medicine and health sciences
                Diagnostic medicine
                Diabetes diagnosis and management
                HbA1c
                Biology and life sciences
                Biochemistry
                Proteins
                Hemoglobin
                HbA1c
                Medicine and Health Sciences
                Cardiology
                Heart Rate
                Medicine and Health Sciences
                Endocrinology
                Endocrine Disorders
                Diabetes Mellitus
                Medicine and Health Sciences
                Metabolic Disorders
                Diabetes Mellitus
                Medicine and Health Sciences
                Public and Occupational Health
                Physical Activity
                Physical Fitness
                Exercise
                Medicine and Health Sciences
                Sports and Exercise Medicine
                Exercise
                Biology and Life Sciences
                Sports Science
                Sports and Exercise Medicine
                Exercise
                Research and Analysis Methods
                Mathematical and Statistical Techniques
                Statistical Methods
                Regression Analysis
                Linear Regression Analysis
                Physical Sciences
                Mathematics
                Statistics (Mathematics)
                Statistical Methods
                Regression Analysis
                Linear Regression Analysis
                Medicine and Health Sciences
                Public and Occupational Health
                Physical Activity
                Medicine and Health Sciences
                Endocrinology
                Diabetic Endocrinology
                Insulin
                Biology and Life Sciences
                Biochemistry
                Hormones
                Insulin
                Biology and Life Sciences
                Anatomy
                Anthropometry
                Medicine and Health Sciences
                Anatomy
                Anthropometry
                Custom metadata
                The authors cannot share the data underlying this study because the data belongs to Profil Institut für Stoffwechselforschung GmbH. Qualified researchers may request data access by contacting Profil Institut für Stoffwechselforschung GmbH ( marketing@ 123456profil.com ). The authors did not have any special access privileges that others would not have. Profil Institut für Stoffwechselforschung GmbH, Hellersbergstraße 9, 41460 - Neuss, Germany, Telephone +49-2131-4018-345, marketing@ 123456profil.com , https://www.profil.com.

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