Asymptomatic ST-depression during exercise testing in children and adolescents with type 1 diabetes mellitus and autonomic dysfunction

Aim.
The aim of this study was to investigate cardiac autonomic function as assessed by ST dynamics during and post-exercise in children and adolescents with type 1 diabetes mellitus (T1DM).
Materials and methods.
The study included 71 young patients with T1DM. The patients were aged 9?18 years and had no history of macrovascular disease or renal disease, including microalbuminuria. Cardiac autonomic function was assessed using cardiovascular tests and 24-h ECG monitoring with automatic calculation of QT interval and heart rate variability parameters. Each patient underwent the physical working capacity 170 test.
Results.
The prevalence of cardiovascular autonomic neuropathy (CAN) was 30.9%. The frequency of asymptomatic ST-segment depression increased during exercise in 10 (45.5%) patients with CAN (CAN+) compared with 9 (18.4%) patients without CAN (CAN-; p=0.042). During the recovery period, asymptomatic ST-segment depression was present in the first minute in 8 (36.4%) CAN+ patients compared with 1 (2%) CAN- patient (p=0.0003) and in the second minute in 5 (22.7%) CAN+ patients compared with 1 (2%) CAN- patient (p=0.0095).
Conclusion.
Children and adolescents with T1DM and impaired autonomic function have increased prevalence of asymptomatic ST-segment depression during and post-exercise. The presence of cardiovascular risk factors in children and adolescents with T1DM and CAN may contribute to the increased cardiovascular morbidity and mortality during adulthood in patients with T1DM.

type 1 diabetes mellitus, cardiovascular autonomic neuropathy, ST-segment, physical working capacity 170, heart rate variability, exercise testing, QT interval

1. de Ferranti SD, de Boer IH, Fonseca V, et al. Type 1 Diabetes Mellitus and Cardiovascular Disease: A Scientific Statement From the American Heart Association and American Diabetes Association. Diabetes care. 2014;37(10):2843-2863. doi: 10.2337/dc14-1720

2. Berenson GS, Srinivasan SR, Bao W, et al. Association between Multiple Cardiovascular Risk Factors and Atherosclerosis in Children and Young Adults. New England Journal of Medicine. 1998;338(23):1650-1656. doi: doi:10.1056/NEJM199806043382302

3. Vinik AI, Ziegler D. Diabetic Cardiovascular Autonomic Neuropathy. Circulation. 2007;115(3):387-397. doi: 10.1161/circulationaha.106.634949

4. Шайдуллина М.Р., Валеева Ф.В., Якупов Э.З. Факторы риска развития диабетической автономной кардиоваскулярной нейропатии у детей и подростков, страдающих сахарным диабетом 1 типа. // Сахарный диабет. – 2013. - №3 – С.84–89. [Shaidullina MR, Valeeva FV, Yakupov E.Z. Risk factors for diabetic autonomic cardiovascular neuropathy in children and adolescents with type 1 diabetes mellitus. Diabetes Mellitus. 2013;(3):84–89.] doi: 10.14341/2072-0351-821

5. Fowler-Brown A, Pignone M, Pletcher M, et al. Exercise tolerance testing to screen for coronary heart disease: a systematic review for the technical support for the U.S. Preventive Services Task Force. Ann Intern Med. 2004;140(7):W9–24. doi:10.7326/0003-4819-140-7-200404060-w1

6. Laukkanen JA, Kurl S, Lakka TA, et al. Exercise-induced silent myocardial ischemia and coronary morbidity and mortality in middle-aged men. Journal of the American College of Cardiology. 2001;38(1):72-79. doi: 10.1016/S0735-1097(01)01311-0.

7. Almeda FQ, Kason TT, Nathan S, Kavinsky CJ. Silent myocardial ischemia: concepts and controversies. The American journal of medicine.116(2):112-118. doi: 10.1016/j.amjmed.2003.09.029

8. Лаптев Д.Н., Рябыкина Г.В., Сеид-Гусейнов А.А. Суточное мониторирование ЭКГ и уровня глюкозы в выявлении зависимости между гликемией и длительностью интервала QT у больных сахарным диабетом 1-го типа. // Терапевтический Архив. - 2009. - Т. 81. - №4. - С.28–33. [Laptev DN, Riabykina GV, Seid-Guseĭnov AA. 24-hours monitoring of ECG and glucose level for detection of relations between glycemia and QT interval duration in patients with type 1 diabetes. Ter Arkhiv. 2009;81(4):28–33.]

9. Лаптев Д.Н., Кружкова М.Н., Рябыкина Г.В.,и соав. Влияние непродолжительной дозированной физической нагрузки на уровень гликемии у детей и подростков, больных сахарным диабетом 1 типа при длительном мониторировании ЭКГ и двигательной активности. // Кардиология. - 2012 - Т. 52. - №6 – С.48–54. [Laptev DN, Kruzhkova MN, Riabykina GV, et al. Effect of short term graded physical exercise on the level of glycemia in children and adolescents with type 1 diabetes mellitus: data of long term ECG monitoring and registration of motor activity. Kardiologiia. 2012;52(6):48–54.]

10. Лаптев Д.Н., Рябыкина ГВ. Аритмогенное действие гипогликемии, регистрируемое при длительном мониторировании ЭКГ у детей и подростков с сахарным диабетом 1 типа. // Сахарный Диабет. – 2013. - №4 – С.22–27. [Laptev DN, Ryabykina GV. Arrhythmogenic effects of hypoglycemia in children and adolescents with type 1 diabetes mellitus. Diabetes Mellitus. 2013;(4):22-27.] doi: 10.14341/DM2013466-71

11. O'Brien IA, O'Hare P, Corrall RJ. Heart rate variability in healthy subjects: effect of age and the derivation of normal ranges for tests of autonomic function. British Heart Journal. 1986;55(4):348-354. doi: 10.1136/hrt.55.4.348

12. Национальные российские рекомендации по применению методики холтеровского мониторирования в клинической практике. // Российский Кардиологический Журнал. – 2013. - Т. 2. - №106 – С.6–71. [National Russian guidelines on application of the methods of Holter monitoring in clinical practice. RussJCardiol 2014; 2(106): 6-71.]

13. Рябыкина Г.В., Соболев А.В. Мониторирование ЭКГ с анализом вариабельности ритма сердца. // М.: Медпрактика-М; 2005. 224 с. [Ryabykina GV, Sobolev AV. Monitorirovanie E'KG s analizom variabel'nosti ritma serdca. Moscow: Medpraktika-M; 2005. 224 p.]

14. Еремина И.А., Лаптев Д.Н., Зильберман Л.И., и соав. Кардиоваскулярная форма автономной нейропатии у подростков с сахарным диабетом 2 типа. // Проблемы эндокринологии. - 2014. - Т. 60. - №5 - С.15-21. [Eremina IA, Laptev DN, Zil’berman LI, et al. The cardiovascular form of autonomous neuropathy in the adolescents with type 2 diabetes mellitus. Problemy Endokrinologii. 2014;60(5):15-21.] doi: 10.14341/probl201460515-2115.

15. Kannel WB, Abbott RD. Incidence and Prognosis of Unrecognized Myocardial Infarction. New England Journal of Medicine. 1984;311(18):1144-1147. doi: doi:10.1056/NEJM198411013111802

16. Deedwania PC, Nelson JR. Pathophysiology of silent myocardial ischemia during daily life. Hemodynamic evaluation by simultaneous electrocardiographic and blood pressure monitoring. Circulation. 1990;82(4):1296-1304. doi: 10.1161/01.cir.82.4.1296

17. Weiner DA, Ryan TJ, McCabe CH, et al. Significance of silent myocardial ischemia during exercise testing in patients with coronary artery disease. American Journal of Cardiology.59(8):725-729. doi: 10.1016/0002-9149(87)91081-2

18. Laukkanen JA, Mäkikallio TH, Rauramaa R, Kurl S. Asymptomatic ST-segment depression during exercise testing and the risk of sudden cardiac death in middle-aged men: a population-based follow-up study. European heart journal. 2009;30(5):558-565. doi: 10.1093/eurheartj/ehn584

19. Klein J, Chao SY, Berman DS, Rozanski A. Is 'silent' myocardial ischemia really as severe as symptomatic ischemia? The analytical effect of patient selection biases. Circulation. 1994;89(5):1958-1966. doi: 10.1161/01.cir.89.5.1958

20. Fleg JL, Tzankoff SP, Lakatta EG. Age-related augmentation of plasma catecholamines during dynamic exercise in healthy males. J Appl Physiol Bethesda Md 1985. 1985;59(4):1033–1039.

21. Wissler RW. An overview of the quantitative influence of several risk factors on progression of atherosclerosis in young people in the United States. Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group. Am J Med Sci. 1995;310 Suppl 1:S29–36. doi: 10.1097/00000441-199512000-00006

22. Valensi P, Sachs R-N, Harfouche B, et al. Predictive Value of Cardiac Autonomic Neuropathy in Diabetic Patients With or Without Silent Myocardial Ischemia. Diabetes care. 2001;24(2):339-343. doi: 10.2337/diacare.24.2.339

23. Лаптев Д.Н., Рябыкина Г.В., Соболев А.В., и соав. Связь гликемии и длительности интервала QT с двигательной активностью у детей и подростков, больных сахарным диабетом 1 типа. // Проблемы Эндокринологии. – 2010. - Т. 56. - №6 – С.24–31. [Laptev DN, Riabykina GV, Sobolev AV, et al. The relationship between the level of glycemia, the length of the QT-interval, and locomotor activity in children and adolescents presenting with type 1 diabetes mellitus. Problemy Endokrinologii. 2010;56(6):24-31. doi: 10.14341/probl201056624-31