Arrhythmogenic effects of hypoglycemia in children and adolescents with type 1 diabetes mellitus
https://doi.org/10.14341/DM2013466-71
Abstract
Aim.
To determine the effects of hypoglycemia on the duration of QT interval, heart rate variability (HRV) and frequency of arrhythmic events, as well as to closer investigate the factors associated with the development of various heart rhythm disorders in children and adolescents with type 1 diabetes mellitus (T1DM).
Materials and methods.
The study included 150 children and adolescents with T1DM at the age of 6?18 years. All participants underwent Holter monitoring and continuous glucose monitoring (CGM) for 24 hours. QTc and HRV parameters (SDNN, RMSSD, SVVR) were calculated automatically. Data was averaged for 5?-interval and juxtaposed with CGM. Patients identified with hypoglycemic events (blood glucose <3.5 mmol/L) during the day (7:00?23:00) and nighttime (23:00?7:00) were selected for further study. In these patients length of QTc and RR intervals, HRV parameters and arrhythmic events were analyzed and collated with CGM data.
Results.
We observed 39 episodes of nocturnal hypoglycaemia in 32 patients (21.3%) and 89 episodes of daytime hypoglycaemia in 46 patients (30.7%). Marked prolongation of QTc (hypo- vs. normoglycemia, respectively: 431 vs. 420 ms; p<0.05) and reduced HRV (hypo- vs. normoglycemia, respectively: SDNN 68 and 90 ms; RMSSD 56 and 61 ms; p <0.05) occurred during episodes of nocturnal hypoglycemia. The same pattern was observed during the day (hypo- vs. normoglycemia, respectively: SDNN 58 and 63 ms; RMSSD 32 and 36 ms; p<0.05). Eleven subjects with nocturnal hypoglycemia demonstrated either ventricular or supraventricular premature complexes. Thirty of subjects with diurnal hypoglycemia also had either ventricular or supraventricular premature complexes. Hypoglycemic episodes vs. normoglycemia were characterized by an increase in ventricular and supraventricular ectopic beats, ST segment and T-wave amplitude depression. Various rhythm abnormalities were associated with cardiovascular autonomic and peripheral neuropathy.
Conclusion.
During episodes of hypoglycemia, HRV parameters decrease, QT elongates and episodes of arrhythmia occur more frequently. History of autonomic and peripheral neuropathy contributes to the development of arrhythmias.
To determine the effects of hypoglycemia on the duration of QT interval, heart rate variability (HRV) and frequency of arrhythmic events, as well as to closer investigate the factors associated with the development of various heart rhythm disorders in children and adolescents with type 1 diabetes mellitus (T1DM).
Materials and methods.
The study included 150 children and adolescents with T1DM at the age of 6?18 years. All participants underwent Holter monitoring and continuous glucose monitoring (CGM) for 24 hours. QTc and HRV parameters (SDNN, RMSSD, SVVR) were calculated automatically. Data was averaged for 5?-interval and juxtaposed with CGM. Patients identified with hypoglycemic events (blood glucose <3.5 mmol/L) during the day (7:00?23:00) and nighttime (23:00?7:00) were selected for further study. In these patients length of QTc and RR intervals, HRV parameters and arrhythmic events were analyzed and collated with CGM data.
Results.
We observed 39 episodes of nocturnal hypoglycaemia in 32 patients (21.3%) and 89 episodes of daytime hypoglycaemia in 46 patients (30.7%). Marked prolongation of QTc (hypo- vs. normoglycemia, respectively: 431 vs. 420 ms; p<0.05) and reduced HRV (hypo- vs. normoglycemia, respectively: SDNN 68 and 90 ms; RMSSD 56 and 61 ms; p <0.05) occurred during episodes of nocturnal hypoglycemia. The same pattern was observed during the day (hypo- vs. normoglycemia, respectively: SDNN 58 and 63 ms; RMSSD 32 and 36 ms; p<0.05). Eleven subjects with nocturnal hypoglycemia demonstrated either ventricular or supraventricular premature complexes. Thirty of subjects with diurnal hypoglycemia also had either ventricular or supraventricular premature complexes. Hypoglycemic episodes vs. normoglycemia were characterized by an increase in ventricular and supraventricular ectopic beats, ST segment and T-wave amplitude depression. Various rhythm abnormalities were associated with cardiovascular autonomic and peripheral neuropathy.
Conclusion.
During episodes of hypoglycemia, HRV parameters decrease, QT elongates and episodes of arrhythmia occur more frequently. History of autonomic and peripheral neuropathy contributes to the development of arrhythmias.
About the Authors
Dmitriy Nikitich Laptev
Endocrinology Research Centre, Moscow
Russian Federation
MD, PhD, Senior Researcher in the Pediatric endocrinology institute
Russian Federation
MD, PhD, Senior Researcher in the Pediatric endocrinology institute
Galina Vladimirovna Ryabykina
Russian Cardiology Research and Production Center, Moscow
Russian Federation
MD, PhD, Professor, Leading Researcher in the Innovative medical technologies department
Russian Federation
MD, PhD, Professor, Leading Researcher in the Innovative medical technologies department
References
1. Donnelly LA, Morris AD, Frier BM, Ellis JD, Donnan PT, Durrant R, et al. Frequency and predictors of hypoglycaemia in Type 1 and insulin-treated Type 2 diabetes: a populationbased study. Diabetic Medicine. 2005;22(6):749–755. DOI: 10.1111/j.1464-5491.2005.01501.x
2. U.K. Hypoglycaemia Study Group. Risk of hypoglycaemia in types 1 and 2 diabetes: effects of treatment modalities and their duration. Diabetologia. 2007;50(6):1140–1147. DOI: 10.1007/s00125-007-0599-y
3. Gill GV, Woodward A, Casson IF, Weston PJ. Cardiac arrhythmia and nocturnal hypoglycaemia in type 1 diabetes--the 'dead in bed' syndrome revisited. Diabetologia. 2009;52(1):42–45. DOI: 10.1007/s00125–008-1177-7
4. Лаптев ДН, Шмушкович ИА. Аритмогенный эффект гипогликемии. Сахарный диабет. 2012;(1):25–30. [Laptev DN, Shmushkovich IA. Arrhythmogenic effects of hypoglycemia. Diabetes mellitus. 2012;(1): 25–30. DOI: 10.14341/2072-0351-5975 ]
5. Amin R, Ross K, Acerini CL, Edge JA, Warner J, Dunger DB. Hypoglycemia Prevalence in Prepubertal Children With Type 1 Diabetes on Standard Insulin Regimen: Use of Continuous Glucose Monitoring System. Diabetes Care. 2003;26(3):662–667. DOI: 10.2337/diacare.26.3.662
6. Seaquist ER, Anderson J, Childs B, Cryer P, Dagogo-Jack S, Fish L, et al. Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society. Diabetes Care. 2013;36(5):1384–1395. DOI: 10.2337/dc12-2480
7. Cryer PE. Death during intensive glycemic therapy of diabetes: mechanisms and implications. American Journal of Medicine. 2011;124(11):993–996. DOI: 10.1016/j.amjmed.2011.08.008
8. Hannonen R, Tupola S, Ahonen T, Riikonen R. Neurocognitive functioning in children with type-1 diabetes with and without episodes of severe hypoglycaemia. Developmental Medicine and Child Neurology. 2003;45(4):262–268. DOI: 10.1111/j.1469-8749.2003.tb00341.x
9. Perantie DC, Lim A, Wu J, Weaver P, Warren SL, Sadler M, et al. Effects of prior hypoglycemia and hyperglycemia on cognition in children with type 1 diabetes mellitus. Pediatric Diabetes. 2008;9(2):87–95. DOI: 10.1111/j.1399-5448.2007.00274.x
10. Northam EA, Anderson PJ, Jacobs R, Hughes M, Warne GL, Werther GA. Neuropsychological Profiles of Children With Type 1 Diabetes 6 Years After Disease Onset. Diabetes Care. 2001;24(9):1541–1546. DOI: 10.2337/diacare.24.9.1541
11. Рябыкина ГВ, Лаптев ДН, Сеид-Гуссейнов АА. Изменение длительности интервала QT у детей и подростков, больных сахарным диабетом 1-го типа. Кардиология. 2007;(12): 35–39. [Ryabykina GV, Laptev DN, Seid-Guseinov AA. Changes of QT-Interval Duration in Children and Adolescents Suffering From Type 1 Diabetes Mellitus. Cargiology. 2007;(12): 35–39]
12. Лаптев ДН, Рябыкина ГВ, Соболев АВ, Кириллов КК, Сеид-Гусейнов АА. Связь гликемии и длительности интервала QT с двигательной активностью у детей и подростков, больных сахарным диабетом 1 типа. Проблемы эндокринологии. 2010; 56(6):24–31. [Laptev D, Riabykina G, Sobolev A, Kirillov K, Seid-Guseĭnov A. 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.]
13. Tanenberg RJ, Newton CA, Drake AJ. Confirmation of hypoglycemia in the "dead-in-bed" syndrome, as captured by a retrospective continuous glucose monitoring system. Endocrine Practice. 2010;16(2):244–248. DOI: 10.4158/EP09260.CR
14. La Rovere MT, Pinna GD, Maestri R, Mortara A, Capomolla S, Febo O, et al. Short-Term Heart Rate Variability Strongly Predicts Sudden Cardiac Death in Chronic Heart Failure Patients. Circulation. 2003;107(4):565–570. DOI: 10.1161/01.cir.0000047275.25795.17
15. Рябыкина ГВ, Соболев АВ. Мониторирование ЭКГ с анализом вариабельности ритма сердца. Москва: Медпрактика-М; 2005. 224 с. [Ryabykina GV, Sobolev AV. Monitorirovanie EKG s analizom variabel'nosti ritma serdtsa. Moscow: Medpraktika-M; 2005. 224 p.]
16. Donaghue KC, Chiarelli F, Trotta D, Allgrove J, Dahl-Jorgensen K. Microvascular and macrovascular complications associated with diabetes in children and adolescents. Pediatric Diabetes. 2009;10(Suppl 12):195–203. DOI: 10.1111/j.1399-5448.2009.00576.x
17. Malik M, Bigger JT, Camm AJ, Kleiger RE, Malliani A, Moss AJ, et al. Heart rate variability: Standards of measurement, physiological interpretation, and clinical use. European Heart Journal. 1996;17(3):354–381.
18. Рябыкина ГВ, Лаптев ДН, Соболев АВ, Сеид-Гуссейнов АА, Волков ИЭ. Исследование интервала QT у детей и подростков, больных сахарным диабетом 1 типа, при холтеровском мониторировании ЭКГ Сахарный диабет. 2007;(2):19–23. [Ryabykina G V et al. Issledovanie intervala QTu detey i podrostkov, bol'nykh sakharnymdiabetom 1 tipa, pri kholterovskommonitorirovanii EKG. Diabetes mellitus. 2007;(2):19–23.DOI: 10.14341/2072-0351-5791 ]
19. Soydan N, Bretzel RG, Fischer B, Wagenlehner F, Pilatz A, Linn T. Reduced capacity of heart rate regulation in response to mild hypoglycemia induced by glibenclamide and physical exercise in type 2 diabetes. Metabolism. 2013 May;62(5):717–724. DOI: 10.1016/j.metabol.2012.12.003
20. Lindstrom T, Jorfeldt L, Tegler L, Arnqvist HJ (1992) Hypoglycaemia and cardiac arrhythmias in patients with type 2 diabetes mellitus. Diabet Med. 1992; 9(6):536–541. DOI: 10.1111/j.1464-5491.1992.tb01834.x
21. Weston PJ, Gill GV. Is undetected autonomic dysfunction responsible for sudden death in type 1 diabetes mellitus? The ‘dead in bed’ syndrome revisited. Diabet Med. 1999 Aug;16(8):626–631. DOI: 10.1046/j.1464-5491.1999.00121.x
22. Karavanaki K, Kazianias G, Kakleas K, Konstantopoulos I, Karayianni C. QT interval prolongation in association with impaired circadian variation of blood pressure and heart rate in adolescents with type 1 diabetes. Diabet Med. 2007 Nov;24(11):1247-1253. DOI: 10.1111/j.1464-5491.2007.02220.x
23. Høi-Hansen T, Pedersen-Bjergaard U, Thorsteinsson B. Reproducibility and reliability of hypoglycaemic episodes recorded with Continuous Glucose Monitoring System (CGMS) in daily life. Diabet Med. 2005 Jul;22(7):858-862. DOI: 10.1111/j.1464-5491.2005.01552.x
Review
For citations:
Laptev D.N., Ryabykina G.V. Arrhythmogenic effects of hypoglycemia in children and adolescents with type 1 diabetes mellitus. Diabetes mellitus. 2013;16(4):66-71. https://doi.org/10.14341/DM2013466-71
Views:
1202
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0).
Email this article 
