Аrterial stiffness and cardiovascular autonomic neuropathy relationship in children and adolescents with type 1 diabetes mellitus

Aim.
To evolve the association between cardiac autonomic function and arterial stiffness in children and adolescents with type 1 diabetes mellitus (T1DM).
Materials and methods.
72 T1DM patients aged 7?18 years without history of macrovascular complications or renal disease, including microalbuminuria, were involved in the study. Cardiac function was assessed by the cardiovascular tests and 24-hour ECG monitoring with automatic calculation of QT interval and heart rate variability (HRV) parameters. Artery stiffness was assessed by measurement of pulse wave velocity (PWV) and augmentation index (AI) obtained from arterial blood pressure monitoring for 24 hours.
Results.
Estimated prevalence of cardiovascular autonomic neuropathy (CAN) was 31,9%. CAN+ patients had significantly higher PWV and AI than those without CAN. A negative correlation between PWV and AI with some cardiovascular tests and HRV parameters was observed. In multivariable analysis, AI was independent predictor of autonomic dysfunction defined as number of positive cardiovascular tests, HRV parameters below normal values and prolongation of QT interval (?.
=0,18; p=0,035).
Conclusion.
Cardiac autonomic function is an independent predictor of arterial stiffness, in children and adolescents with T1D without macrovascular and renal complications. The presence of cardiovascular risk factors and arterial stiffness in children and adolescents with T1DM may contribute to the increased cardiovascular morbidity and mortality in adulthood in patients with CAN.

type 1 diabetes mellitus, autonomic neuropathy, heart rate variability, arterial stiffness, blood pressure, QT interval

1. Yoon JM. Dyslipidemia in Children and Adolescents: When and How to Diagnose and Treat? Pediatric Gastroenterology, Hepatology & Nutrition. 2014;17(2):85–92. doi: 10.5223/pghn.2014.17.2.85

2. Benetos A, Lacolley P. From 24-Hour Blood Pressure Measurements to Arterial Stiffness: A Valid Short Cut? Hypertension. 2006;47(3):327–328. doi: 10.1161/01.hyp.0000200705.61571.95

3. Федорова С.И., Кулаков Н.В., Дерзанов А.В., Пронина В.П. Валидация показателей ригидности сосудов и параметров гемодинамики, определенных с использованием модели распространения пульсовой волны. // Терапевт. – 2014. – №8. – С. 51–60. [Fyodorova SI, Kulakov NV, Derzanov AV, Pronina VP. Validation of vascular rigidity indexes and parameters of hemodynamic, determined by means of the model of pulse wave expansion. Terapevt. 2014;(8):51–60.]

4. Dabelea D, Talton JW, D’Agostino R, et al. Cardiovascular Risk Factors Are Associated With Increased Arterial Stiffness in Youth With Type 1 Diabetes: The SEARCH CVD study. Diabetes care. 2013;36(12):3938–3943. doi: 10.2337/dc13-0851

5. Doneen AL, Bale BF. Carotid intima-media thickness testing as an asymptomatic cardiovascular disease identifier and method for making therapeutic decisions. Postgrad Med. 2013;125:108–123. doi:10.3810/pgm.2013.03.2645

6. Vinik AI, Erbas T, Casellini CM. Diabetic cardiac autonomic neuropathy, inflammation and cardiovascular disease. Journal of Diabetes Investigation. 2013;4(1):4–18. doi: 10.1111/jdi.12042.

7. Кулакова Е.В., Кулаков Н.В., Федорова С.И. Тестирование осциллометрического и аускультативного режимов работы монитора МЭКГ-ДП-НС-01 по протоколам ESH, BHS и AAMI. // Альманах Клинической Медицины. – 2014. – №31. – С. 34–39. [Fedorova SI, Kulakov NV, Kulakova EV. Validation of the MECG-DP-NS-01 monitor in oscillometry and auscultation modes, according to ESH, BHS and AAMI protocols. Almanac of clinical medicine. 2014;(31):34–39.]

8. Лаптев Д.Н., Кружкова М.Н., Рябыкина Г.В., и др. 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. – №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.]

9. Лаптев Д.Н., Рябыкина Г.В. Аритмогенное действие гипогликемии, регистрируемое при длительном мониторировании ЭКГ у детей и подростков с сахарным диабетом 1 типа. // Сахарный диабет. – 2013. – №4. – С. 22–7. [Laptev DN, Ryabykina GV. Arrhythmogenic effects of hypoglycemia in children and adolescents with type 1 diabetes mellitus. Diabetes Mellitus. 2013; 18;(4):66.] doi: 10.14341/DM2013466-71

10. Александров А.А., Кисляк О.А., Леонтьева И.В., Розанова В.Б. Диагностика, лечение и профилактика артериальной гипертензии у детей и подростков. // Кардиоваскулярная Терапия и Профилактика. – 2009. – Т.8. – №S8. – С. 2–32. [Aleksandrov AA, Kislyak OA, Leont'eva IV, Rozanova VB. Diagnostika, lechenie i profilaktika arterial'noj gipertenzii u detej i podrostkov. Cardiovascular therapy and prevention. 2009;8(S8):2–32.]

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.

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. Russian journal of cardiology. 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. ECG Monitoring with rhythm variability analysis. Mosсow: Medpraktika-M; 2005. 224 p.]

14. Haller MJ, Samyn M, Nichols WW, et al. Radial Artery Tonometry Demonstrates Arterial Stiffness in Children With Type 1 Diabetes. Diabetes care. 2004;27(12):2911–2917. doi: 10.2337/diacare.27.12.2911

15. Liatis S, Alexiadou K, Tsiakou A, et al. Cardiac Autonomic Function Correlates with Arterial Stiffness in the Early Stage of Type 1 Diabetes. Experimental Diabetes Research. 2011;2011:957901. doi: 10.1155/2011/957901

16. Palatini P, Casiglia E, Gąsowski J, et al. Arterial stiffness, central hemodynamics, and cardiovascular risk in hypertension. Vascular Health and Risk Management. 2011;7:725–739. doi: 10.2147/VHRM.S25270.

17. Farkas K, Jermendy G, Herold M, et al. Impairment of the NO/cGMP pathway in the fasting and postprandial state in type 1 diabetes mellitus. Experimental and clinical endocrinology & diabetes: official journal, German Society of Endocrinology [and] German Diabetes Association. 2004;112(5):258–263. doi: 10.1055/s-2004-817973

18. Frattola A, Parati G, Gamba P, et al. Time and frequency domain estimates of spontaneous baroreflex sensitivity provide early detection of autonomic dysfunction in diabetes mellitus. Diabetologia. 1997;40(12):1470–1475. doi: 10.1007/s001250050851

19. Mircoli L, Mangoni AA, Giannattasio C, et al. Heart rate-dependent stiffening of large arteries in intact and sympathectomized rats. Hypertension. 1999;34(4 Pt 1):598–602.

20. MacFadyen RJ, Lim HS. Emergence of structural arterial stiffness in diabetes and the role of abnormalities of autonomic tone in the sequence of events. Journal of human hypertension. 2004;18(11):755–756. doi: 10.1038/sj.jhh.1001755

21. Prince CT, Secrest AM, Mackey RH, et al. Cardiovascular autonomic neuropathy, HDL cholesterol, and smoking correlate with arterial stiffness markers determined 18 years later in type 1 diabetes. Diabetes care. 2010;33(3):652–657. doi: 10.2337/dc09-1936

22. Orchard TJ, Forrest KY, Kuller LH, et al. Lipid and blood pressure treatment goals for type 1 diabetes: 10-year incidence data from the Pittsburgh Epidemiology of Diabetes Complications Study. Diabetes care. 2001;24(6):1053–1059.

23. Li S, Chen W, Srinivasan SR, et al. Childhood cardiovascular risk factors and carotid vascular changes in adulthood: the Bogalusa Heart Study. Jama. 2003;290(17):2271–2276. DOI: 10.1001/jama.290.17.2271.