2564 Diabetes Care Volume 43, October 2020 Elodie Lespagnol,1 Olivia Bocock,2,3 In Amateur Athletes With Type 1 Joris Heyman,4 François-Xavier Gamelin,1 Serge Berthoin,1 Bruno Pereira,5 Diabetes, a 9-Day Period of Julien Boissiere,` 1 Martine Duclos,2,3 and Cycling at Moderate-to-Vigorous Elsa Heyman1 Intensity Unexpectedly Increased the Time Spent in Hyperglycemia, Which Was Associated With Impairment in Heart Rate Variability Diabetes Care 2020;43:2564–2573 | https://doi.org/10.2337/dc19-1928 OBJECTIVE In type 1 diabetes, autonomic dysfunction may occur early as a decrease in heart rate variability (HRV). In populations without diabetes, the positive effects of exercise training on HRV are well-documented. However, exercise in individuals 1ULR 7369 - URePSSS - Unite´ de Recherche with type 1 diabetes, particularly if strenuous and prolonged, can lead to sharp Pluridisciplinaire Sport Sante´ Societ´ e,´ Universite´ glycemic variations, which can negatively impact HRV. This study explores the de Lille, Universited´ ’Artois, Universite´ du Littoral ˆ ’ impact of a 9-day cycling tour on HRV in this population, with a focus on exercise- Cote d Opale, Lille, France 2Unite´ de Nutrition Humaine, INRA, UMR 1019, induced glycemic excursions. UNH, CRNH Auvergne, Clermont Universite,´ Uni- versited´ ’Auvergne, Clermont-Ferrand, France RESEARCH DESIGN AND METHODS 3Service de Medecinedu´ Sport et des Explorations Twenty amateur athletes with uncomplicated type 1 diabetes cycled 1,500 km. HRV and Fonctionnelles, CHU Clermont-Ferrand, Clermont- glycemic variability were measured by heart rate and continuous glucose monitoring. Ferrand, France 4CNRS, UMR 6118: Transferts d’eau et de matiere` Linear mixed models were used to test the effects of exercise on HRV, with concomitant dans les milieux het´ erog´ enes` complexes – glycemic excursions and subject characteristics considered as covariates. Geosciences,´ UniversiteRennes1,Rennes,´ France RESULTS 5Unite´ de Biostatistiques (DRCI), CHU Clermont- Nighttime HRV tended to decrease with the daily distance traveled. The more time Ferrand, Clermont-Ferrand, France the subjects spent in hyperglycemia, the lower the parasympathetic tone was. This Corresponding author: Elsa Heyman, elsa.heyman @univ-lille.fr result is striking given that hyperglycemic excursions progressively increased through- Received 27 September 2019 and accepted 19 CARDIOVASCULAR AND METABOLIC RISK out the 9 days of the tour, and to a greater degree on the days a longer distance was June 2020 traveled, while time spent in hypoglycemia surprisingly decreased. This phenomenon This article contains supplementary material on- occurred despite no changes in insulin administration and a decrease in carbohydrate line at https://doi.org/10.2337/figshare.12517397. intake from snacks. M.D. and E.H. share the responsibility for this study on behalf of the Physical Activity Group CONCLUSIONS from Societ´ e´ Francophone du Diabete.` In sports enthusiasts with type 1 diabetes, multiday prolonged exercise at moderate- © 2020 by the American Diabetes Association. to-vigorous intensity worsened hyperglycemia, with hyperglycemia negatively asso- Readers may use this article as long as the work is ciated with parasympathetic cardiac tone. Considering the putative deleterious properly cited, the use is educational and not for profit, and the work is not altered. More infor- consequences on cardiac risks, future work should focus on understanding and mation is available at https://www.diabetesjournals managing exercise-induced hyperglycemia. .org/content/license. care.diabetesjournals.org Lespagnol and Associates 2565 In type 1 diabetes, cardiac autonomic blood glucose values, registered over a (Polar H7) to assess HRV at night plus neuropathy results from dysfunction of regular 5-day period, was associated with during time spent at different exercise sympathetic and/or parasympathetic ner- impaired HRV in adults with type 1 di- intensities during cycling (12). vous system activity and is associated with abetes (9). However, the literature offers Helped by the onsite dietitian, riders an increased risk of ventricular arrhythmia no data about cardiac autonomic activity reported their self-estimation of carbo- and cardiovascular morbidity and mortal- changes accompanying exercise-induced hydrates consumed at every meal (break- ity (1). Long before the appearance of glycemicfluctuations,eventhoughexercise- fast, lunch, and dinner). The day prior to autonomic neuropathy clinical signs, sub- induced hypoglycemic episodes may ap- the start of the tour, riders were inter- tle cardiac autonomic dysfunction can pear long (24 h) after the exercise session. viewed by the dietitian to assess their manifest as a decrease in heart rate var- Theaimof thisobservationalstudywas ability to accurately count carbohydrates. iability (HRV) and its components (2). A to explore, in riders with uncomplicated Those who were less accustomed to this large body of literature describes an al- type 1 diabetes, the impact of a 9-day practice benefited from a closer follow-up tered parasympathetic tone in individuals cycling tour on HRV, taking into consid- by the dietitian throughout the tour. with uncomplicated type 1 diabetes com- eration concomitant exercise-induced gly- Riders also reported the exact times and pared with healthy control subjects, result- cemic excursions and their influencing types of snacks consumed. For better ing in relative sympathetic overactivity (2). factors (i.e., diet and insulin). standardization, they were encouraged In an 11-year follow-up study of 83 sub- to use the gels, bars, and recovery drinks jects with type 1 diabetes, Makimattila¨ RESEARCH DESIGN AND METHODS provided by the staff. Among the 13 in- et al. (2) showed that chronic hypergly- Subjects dividuals treated with continuous sub- cemia (high HbA1c) was a strong predictor Twenty-three riders agreed to participate cutaneous insulin infusion (CSII), 8 made of a lower HRV. Chronic hyperglycemia in this investigation,traveling the 1,456 km their insulin pump data available for the might be attenuated by interventions such that separates Brussels and Geneva over study analyses. Every morning of the as exercise training (3), which has indeed 10 days (mHealth Grand Tour, 3–12 Sep- tour, just before breakfast, blood pres- been suggested as a way to improve HRV tember 2015), including a recovery day sure and body composition (bioelectric in type 1 diabetes (4,5). (day 4) (Supplementary Table 1). The in- impedance) were noted. Data from the However, aerobic exercise, particularly clusion criteria were age $18 years, a heart rate monitor, CGMs, carbohydrate when prolonged, intense, and/or unusual, history of type 1 diabetes for .1year,an intake, capillary blood glucose, and symp- may also trigger glycemic variability (6). HbA1c (dating back no more than 3 months) tomatic (awareness) episodes of hypogly- Hypoglycemic episodes are common due ,9% (75 mmol z mol21), and to have cemia were gathered via Bluetooth on to the increased muscle glucose disposal already experienced a 1-day ride .160 km smartphones and thereafter downloaded associated with high peripheral insulin as well as rides of 100 km on consecutive withspecificsoftwareforfurtheranalyses. concentrations, while nondecreased insu- days. All participants were free from overt lin levels in the portal vein prevent glucose micro- and macrovascular complications, HRV Analysis release from the liver. Transient hypergly- except one who suffered from arterio- The HRV analysis was performed with cemic episodes may also occur, for exam- pathy; thus, the latter was excluded from Kubios HRV software in accordance with ple, during early recovery from intense the analyses. Written informed consent the Task Force of the European Society of exercise performed in a postabsorptive was obtained, and data collection was Cardiology and the North American Society state. Notably, it is not only sedentary or granted approval by Commission Natio- for Pacing and Electrophysiology (13). HRV inactive patients who are prone to these nale de l’Informatique et des Libertes´ was analyzed during a standardized calm exercise-induced glycemic fluctuations but (CNIL) (MMS/TDG/ALU/AE151191). Usual (sleeping) period between midnight and also the increasing number of sports en- physical activity was assessed using the 4:00 A.M. throughout the 9 days of cycling. thusiasts with type 1 diabetes engaging in short version of the International Physical We analyzed time domain parameters (SD outdoor ultra-endurance events. Activity Questionnaire. Additionally, 10 riders of normal to normal R-R [SDNN]), (percent- Interestingly, outside the context of had undergone an incremental maximal age of differences .50 ms between suc- exercise, it has been suggested that acute exercise test (VO2max) as part of inde- cessive NN intervals [pNN50]), and the root glycemic excursions impair cardiac auto- pendent medical monitoring of athletes. mean square of differences of successive nomic activity. Thus, Nguyen et al. (7) Whether participants suffered from hy- NN intervals [RMSSD]) as well as frequency provided pilot data in six subjects with poglycemia unawareness was also re- domains of HRV by the Fast Fourier Trans- – type 1 diabetes, showing that periods of ported. According to VO2max or training form (high frequency [HF], 0.15 0.40 Hz, naturally occurring hyperglycemia (mea- status,theparticipantswererecreationally and low frequency [LF], 0.04–0.15 Hz). suredoveronenight)wereassociatedwith