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Ilhan, Z., Bekdas, M., Inanir, M., & Kabakus, N. (2022). Insulin Resistance and Other Comorbidities of Obesity as Independent Variables on Ventricular Repolarization in Children and Adolescents. Sudan Journal of Medical Sciences (SJMS), 17(2), 157–169. https://doi.org/10.18502/sjms.v17i2.11451
https://doi.org/10.18502/sjms.v17i2.11451
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Zehra Ilhan
Zehra Ilhan
1Department of Pediatrics, Bolu Abant Izzet Baysal University Medical Faculty, Bolu, Turkey
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Mervan Bekdas
Mervan Bekdas
Department of Pediatrics, Bolu Abant Izzet Baysal University Medical Faculty, Bolu, Turkey
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Mehmet Inanir
Mehmet Inanir
Department of Cardiology, Bolu Abant Izzet Baysal University Medical Faculty, Bolu, Turkey
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Nimet Kabakus
Nimet Kabakus
Department of Pediatrics, Bolu Abant Izzet Baysal University Medical Faculty, Bolu, Turkey
Published Date
- Jun 30, 2022
Insulin Resistance and Other Comorbidities of Obesity as Independent Variables on Ventricular Repolarization in Children and Adolescents
Abstract
Background: Obesity, a rapidly increasing global health problem in all age groups, is accepted as the basis for many chronic diseases through insulin resistance mechanism. This study aimed to examine whether insulin resistance and other comorbidities of obesity have an effect on the cardiac conduction system.
Methods: The study included 50 obese and 47 healthy individuals aged 6–18 years. ECGs of all cases were taken; ECG waves and intervals were measured manually.
Results: Of the obese group, 19 were boys (38%) and 31 were girls (62%), 27 were children (54%) and 23 were adolescents (46%), their ages were 11.3 ± 3.5 years. These particular characteristics were similar compared to the control group. However, in the obese group, the ECG parameters QTc (p = 0.001), QTd (p < 0.001), QTdc (p < 0.001), JTc (p < 0.001), Tp-e (p < 0.001), Tp-e/QT (p < 0.001), Tp-e/QTc (p < 0.001), Tp-e/JT (p < 0.001), and Tp-e/JTc (p < 0.001) were significantly longer. Twenty-five obese subjects (50%) had insulin resistance, when ECG parameters are compared to those without it, only JTc was significantly longer (332.3 ± 16.5 vs 321.7 ± 17.7 ms, p = 0.033). JTc duration mostly affected JT (p < 0.001) and QTc (p < 0.001). The 327 ms cut-off value of JTc indicated insulin resistance in the obese patients (p = 0.044) (sensitivity 60%, specificity 60%).
Conclusion: Insulin resistance and other comorbidities of obesity may cause ventricular repolarization abnormalities at an early age. JTc, an ECG parameter, can be a guide in assessing ventricular repolarization abnormality and the risk of arrhythmia in these patients.
Keywords: obesity, insulin resistance, comorbidities, ventricular repolarization, child, adolescence
References
[1] WHO. (2004). Obesity: Preventing and managing the global epidemic. WHO. Retrieved from: https://www.who.int
[2] WHO. (2016). WHO European Childhood Obesity Surveillance Initiative (COSI). WHO. Retrieved from: https://www.who.int/europe/initiatives/who-europeanchildhood- obesity-surveillance-initiative-(cosi)
[3] WHO. (2020). Obesity and overweight. WHO. Retrieved from: https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight
[4] Ozcebe, H. and Bosi, A. T. B. (2014). Türkiye çocukluk çağı (7- 8 yaş) şişmanlık araştırması (COSI-TUR) 2013. Retrieved from: https://hsgm.saglik.gov.tr/tr/beslenmehareket-yayinlar1/beslenmehareketkitaplar/ 270.html
[5] Ozcebe, H., Bosi, A. T. B., Yardım, M. S., et al. (2017). Türkiye çocukluk çağı (İlkokul 2. sınıf öğrencileri) şişmanlık araştırması COSI-TUR 2016. Retrieved from: https://hsgm.saglik.gov.tr/depo/haberler/turkiye-cocukluk-cagi-sismanlik/COSITUR- 2016-Kitap.pdf
[6] Bereket, A. and Atay, Z. (2012). Current status of childhood obesity and its associated morbidities in Turkey. Journal of Clinical Research in Pediatric Endocrinology, vol. 4, no. 1, pp. 1–7.
[7] Tam, A. A. and Cakir, B. (2012). Approach of obesity in primary health care. Ankara Medical Journal, vol. 12, pp. 37–41.
[8] Ascaso, J. F., Pardo, S., Real, J. T., et al. (2003). Diagnosing insulin resistance by simple quantitative methods in subjects with normal glucose metabolism. Diabetes Care, vol. 26, no. 12, pp. 3320–3325.
[9] Algra, A., Tijssen, J. G., Roelandt, J. R., et al. (1991). QTc prolongation measured by standard 12-lead electrocardiography is an independent risk factor for sudden death due to cardiac arrest. Circulation, vol. 83, no. 6, pp. 1888–1894.
[10] Straus, S. M. J. M., Kors, J. A., De Bruin, M. L., et al. (2006). Prolonged QTc interval and risk of sudden cardiac death in a population of older adults. Journal of the American College of Cardiology, vol. 47, no. 2, pp. 362–367.
[11] Ashar, F. N., Mitchell, R. N., Albert, C. M., et al. (2018). A comprehensive evaluation of the genetic architecture of sudden cardiac arrest. European Heart Journal, vol. 39, no. 44, pp. 3961–3969.
[12] Haruta, D., Matsuo, K., Tsuneto, A., et al. (2011). Incidence and prognostic value of early repolarization pattern in the 12-lead electrocardiogram. Circulation, vol. 123, pp. 2931–2937.
[13] Tikkanen, J. T., Anttonen, O., Junttila, M. J., et al. (2009). Long-term outcome associated with early repolarization on electrocardiography. The New England Journal of Medicine, vol. 361, no. 26, pp. 2529–2537.
[14] Sinner, M. F., Reinhard, W., Muller, M., et al. (2010). Association of early repolarization pattern on ECG with risk of cardiac and all-cause mortality: A population-based prospective cohort study (MONICA/KORA). PLoS Medicine, vol. 7, no. 7, p. e1000314
[15] Haïssaguerre, M., Derval, N., Sacher, F., et al. (2008). Sudden cardiac arrest associated with early repolarization. NEJM, vol. 358, no. 19, pp. 2016–2023.
[16] Nam, G. B., Kim, Y. H., and Antzelevitch, C. (2008). Augmentation of J waves and electrical storms in patients with early repolarization. NEJM, vol. 358, no. 19, pp. 2078–2079.
[17] Matthews, D. R., Hosker, J. P., Rudenski, A. S., et al. (1985). Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia, vol. 28, no. 7, pp. 412–419.
[18] Kurtoglu, S., Hatipoğlu, N., Mazıcıoğlu, M., et al. (2010). Insulin resistance in obese children and adolescents: HOMA-IR cut-off levels in the prepubertal and pubertal periods. Journal of Clinical Research in Pediatric Endocrinology, vol. 2, no. 3, pp. 100–106.
[19] Franz, M. R., Bargheer, K., Rafflenbeul, W., et al. (1987). Monophasic action potential mapping in human subjects with normal electrocardiograms: Direct evidence for the genesis of the T wave. Circulation, vol. 75, no. 2, pp. 379–386.
[20] Kors, J. A., Ritsema van Eck, H. J., and van Herpen, G. (2008). The meaning of the Tp-Te interval and its diagnostic value. Journal of Electrocardiology, vol. 41, no. 6, pp. 575–580.
[21] Gupta, P., Patel, C., Patel, H., et al. (2008). Tp-e/QT ratio as an index of arrhythmogenesis. Journal of Electrocardiology, vol. 41, no. 6, pp. 567–574.
[22] Helbing, W. A., Roest, A. A., Niezen, R. A., et al. (2002). ECG predictors of ventricular arrhythmias and biventricular size and wall mass in tetralogy of Fallot with pulmonary regurgitation. Heart, vol. 88, no. 5, pp. 515–520.
[23] Ren, X., Chen, Z. A., Zheng, S., et al. (2016). Association between triglyceride to HDLC Ratio (TG/HDL-C) and insulin resistance in Chinese patients with newly diagnosed type 2 diabetes mellitus. PLoS One, vol. 11, no. 4, pp. 1–13.
[24] Gokcel, A., Baltali, M., Tarim, E., et al. (2003). Detection of insulin resistance in Turkish adults: a hospital-based study. Diabetes, Obesity and Metabolism, vol. 5, no. 2, pp. 126–130.
[25] Ehtisham, S. and Barrett, T. G. (2004). The emergence of type 2 diabetes in childhood. Annals of Clinical Biochemistry, vol. 41, no. 1, pp. 10–16.
[26] Whitlock, G., Lewington, S., Sherliker, P., et al. (2009). Body-mass index and causespecific mortality in 900000 adults: Collaborative analyses of 57 prospective. Lancet, vol. 373, no. 9669, pp. 1083–1096.
[27] Zhang, Y. and Ren, J. (2016). Epigenetics and obesity cardiomyopathy: From pathophysiology to prevention and management. Pharmacology & Therapeutics, vol. 161, pp. 52–66.
[28] Rizzo, C., Monitillo, F., and Iacoviello, M. (2016). 12-lead electrocardiogram features of arrhythmic risk: A focus on early repolarization. World Journal of Cardiology, vol. 8, no. 8, pp. 447–455.
[29] Daar, G., Serin, H. İ., Ede, H., et al. (2016). Association between the corrected QT interval, carotid artery intima- media thickness, and hepatic steatosis in obese children. The Anatolian Journal of Cardiology, vol. 16, no. 7, pp. 524–528.
[30] Güven, A., Özgen, T., Güngör, O., et al. (2010). Association between the corrected QT interval and carotid artery intima-media thickness in obese children. Journal of Clinical Research in Pediatric Endocrinology, vol. 2, no. 1, pp. 21–27.
[31] Roden, D. M. (2004). Drug-induced prolongation of the QT interval. NEJM, vol. 350, pp. 1013–1022.
[32] Antzelevitch, C., Sicouri, S., Di Diego, J. M., et al. (2007). Does Tpeak-Tend provide an index of transmural dispersion of repolarization? Heart Rhythm, vol. 4, no. 8, pp. 1114–1116.
[33] Smetana, P., Schmidt, A., Zabel, M., et al. (2011). Assessment of repolarization heterogeneity for prediction of mortality in cardiovascular disease: Peak to the end of the T wave interval and nondipolar repolarization components. Journal of Electrocardiology, vol. 44, no. 3, pp. 301–308.
[34] Maury, P., Sacher, F., Gourraud, J. B., et al. (2015). Increased Tpeak-Tend interval is highly and independently related to arrhythmic events in Brugada syndrome. Heart Rhythm, vol. 12, no. 12, pp. 2469–2476.
[35] Karaman, K., Altunkaş, F., Çetin, M., et al. (2015). New markers for ventricular repolarization in coronary slow flow: Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio. Annals of Noninvasive Electrocardiology, vol. 20, no. 4, pp. 338–344.
[36] Mugnai, G., Hunuk, B., Hernandez-Ojeda, J., et al. (2017). Role of electrocardiographic Tpeak-Tend for the prediction of ventricular arrhythmic events in the Brugada syndrome. The American Journal of Cardiology, vol. 120, no. 8, pp. 1332–1337.
[37] Banker, J., Dizon, J., and Reiffel, J. (1997). Effects of the ventriküler activation sequence on the JT interval. The American Journal of Cardiology, vol. 79, no. 6, pp. 816–819.
[38] Inanir, M., Sincer, I., Erdal, E., et al. (2019). Evaluation of electrocardiographic ventricular repolarization parameters in extreme obesity. Journal of Electrocardiology, vol. 53, pp. 36–39.
[39] El-Eraky, H. and Thomas, S. H. (2003). Effects of sex on the pharmacokinetic and pharmacodynamic properties of quinidine. British Journal of Clinical Pharmacology, vol. 56, no. 2, pp. 198–204.
[40] Chan, S., Motonaga, K., Hollander, S., et al. (2016). Electrocardiographic repolarization abnormalities and increased risk of life-threatening arrhythmias in children with dilated cardiomyopathy. Heart Rhythm, vol. 13, no. 6, pp. 1289–1296.
[41] Das, B. B. and Sharma, J. (2004). Repolarization abnormalities in children with a structurally normal heart and ventricular ectopy. Pediatric Cardiology, vol. 25, no. 4, pp. 354–356.
[42] Nigro, G., Russo, V., Di Salvo, G., et al. (2010). Increased heterogenity of ventricular repolarization in obese nonhypertensive children. Pacing and Clinical Electrophysiology, vol. 33, no. 12, pp. 1533–1539.
[43] Kannel, W. B., Plehn, J. F., and Cupples, L. A. (1988). Cardiac failure and sudden death in the Framingham Study. American Heart Journal, vol. 115, no. 4, pp. 869–875.
[2] WHO. (2016). WHO European Childhood Obesity Surveillance Initiative (COSI). WHO. Retrieved from: https://www.who.int/europe/initiatives/who-europeanchildhood- obesity-surveillance-initiative-(cosi)
[3] WHO. (2020). Obesity and overweight. WHO. Retrieved from: https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight
[4] Ozcebe, H. and Bosi, A. T. B. (2014). Türkiye çocukluk çağı (7- 8 yaş) şişmanlık araştırması (COSI-TUR) 2013. Retrieved from: https://hsgm.saglik.gov.tr/tr/beslenmehareket-yayinlar1/beslenmehareketkitaplar/ 270.html
[5] Ozcebe, H., Bosi, A. T. B., Yardım, M. S., et al. (2017). Türkiye çocukluk çağı (İlkokul 2. sınıf öğrencileri) şişmanlık araştırması COSI-TUR 2016. Retrieved from: https://hsgm.saglik.gov.tr/depo/haberler/turkiye-cocukluk-cagi-sismanlik/COSITUR- 2016-Kitap.pdf
[6] Bereket, A. and Atay, Z. (2012). Current status of childhood obesity and its associated morbidities in Turkey. Journal of Clinical Research in Pediatric Endocrinology, vol. 4, no. 1, pp. 1–7.
[7] Tam, A. A. and Cakir, B. (2012). Approach of obesity in primary health care. Ankara Medical Journal, vol. 12, pp. 37–41.
[8] Ascaso, J. F., Pardo, S., Real, J. T., et al. (2003). Diagnosing insulin resistance by simple quantitative methods in subjects with normal glucose metabolism. Diabetes Care, vol. 26, no. 12, pp. 3320–3325.
[9] Algra, A., Tijssen, J. G., Roelandt, J. R., et al. (1991). QTc prolongation measured by standard 12-lead electrocardiography is an independent risk factor for sudden death due to cardiac arrest. Circulation, vol. 83, no. 6, pp. 1888–1894.
[10] Straus, S. M. J. M., Kors, J. A., De Bruin, M. L., et al. (2006). Prolonged QTc interval and risk of sudden cardiac death in a population of older adults. Journal of the American College of Cardiology, vol. 47, no. 2, pp. 362–367.
[11] Ashar, F. N., Mitchell, R. N., Albert, C. M., et al. (2018). A comprehensive evaluation of the genetic architecture of sudden cardiac arrest. European Heart Journal, vol. 39, no. 44, pp. 3961–3969.
[12] Haruta, D., Matsuo, K., Tsuneto, A., et al. (2011). Incidence and prognostic value of early repolarization pattern in the 12-lead electrocardiogram. Circulation, vol. 123, pp. 2931–2937.
[13] Tikkanen, J. T., Anttonen, O., Junttila, M. J., et al. (2009). Long-term outcome associated with early repolarization on electrocardiography. The New England Journal of Medicine, vol. 361, no. 26, pp. 2529–2537.
[14] Sinner, M. F., Reinhard, W., Muller, M., et al. (2010). Association of early repolarization pattern on ECG with risk of cardiac and all-cause mortality: A population-based prospective cohort study (MONICA/KORA). PLoS Medicine, vol. 7, no. 7, p. e1000314
[15] Haïssaguerre, M., Derval, N., Sacher, F., et al. (2008). Sudden cardiac arrest associated with early repolarization. NEJM, vol. 358, no. 19, pp. 2016–2023.
[16] Nam, G. B., Kim, Y. H., and Antzelevitch, C. (2008). Augmentation of J waves and electrical storms in patients with early repolarization. NEJM, vol. 358, no. 19, pp. 2078–2079.
[17] Matthews, D. R., Hosker, J. P., Rudenski, A. S., et al. (1985). Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia, vol. 28, no. 7, pp. 412–419.
[18] Kurtoglu, S., Hatipoğlu, N., Mazıcıoğlu, M., et al. (2010). Insulin resistance in obese children and adolescents: HOMA-IR cut-off levels in the prepubertal and pubertal periods. Journal of Clinical Research in Pediatric Endocrinology, vol. 2, no. 3, pp. 100–106.
[19] Franz, M. R., Bargheer, K., Rafflenbeul, W., et al. (1987). Monophasic action potential mapping in human subjects with normal electrocardiograms: Direct evidence for the genesis of the T wave. Circulation, vol. 75, no. 2, pp. 379–386.
[20] Kors, J. A., Ritsema van Eck, H. J., and van Herpen, G. (2008). The meaning of the Tp-Te interval and its diagnostic value. Journal of Electrocardiology, vol. 41, no. 6, pp. 575–580.
[21] Gupta, P., Patel, C., Patel, H., et al. (2008). Tp-e/QT ratio as an index of arrhythmogenesis. Journal of Electrocardiology, vol. 41, no. 6, pp. 567–574.
[22] Helbing, W. A., Roest, A. A., Niezen, R. A., et al. (2002). ECG predictors of ventricular arrhythmias and biventricular size and wall mass in tetralogy of Fallot with pulmonary regurgitation. Heart, vol. 88, no. 5, pp. 515–520.
[23] Ren, X., Chen, Z. A., Zheng, S., et al. (2016). Association between triglyceride to HDLC Ratio (TG/HDL-C) and insulin resistance in Chinese patients with newly diagnosed type 2 diabetes mellitus. PLoS One, vol. 11, no. 4, pp. 1–13.
[24] Gokcel, A., Baltali, M., Tarim, E., et al. (2003). Detection of insulin resistance in Turkish adults: a hospital-based study. Diabetes, Obesity and Metabolism, vol. 5, no. 2, pp. 126–130.
[25] Ehtisham, S. and Barrett, T. G. (2004). The emergence of type 2 diabetes in childhood. Annals of Clinical Biochemistry, vol. 41, no. 1, pp. 10–16.
[26] Whitlock, G., Lewington, S., Sherliker, P., et al. (2009). Body-mass index and causespecific mortality in 900000 adults: Collaborative analyses of 57 prospective. Lancet, vol. 373, no. 9669, pp. 1083–1096.
[27] Zhang, Y. and Ren, J. (2016). Epigenetics and obesity cardiomyopathy: From pathophysiology to prevention and management. Pharmacology & Therapeutics, vol. 161, pp. 52–66.
[28] Rizzo, C., Monitillo, F., and Iacoviello, M. (2016). 12-lead electrocardiogram features of arrhythmic risk: A focus on early repolarization. World Journal of Cardiology, vol. 8, no. 8, pp. 447–455.
[29] Daar, G., Serin, H. İ., Ede, H., et al. (2016). Association between the corrected QT interval, carotid artery intima- media thickness, and hepatic steatosis in obese children. The Anatolian Journal of Cardiology, vol. 16, no. 7, pp. 524–528.
[30] Güven, A., Özgen, T., Güngör, O., et al. (2010). Association between the corrected QT interval and carotid artery intima-media thickness in obese children. Journal of Clinical Research in Pediatric Endocrinology, vol. 2, no. 1, pp. 21–27.
[31] Roden, D. M. (2004). Drug-induced prolongation of the QT interval. NEJM, vol. 350, pp. 1013–1022.
[32] Antzelevitch, C., Sicouri, S., Di Diego, J. M., et al. (2007). Does Tpeak-Tend provide an index of transmural dispersion of repolarization? Heart Rhythm, vol. 4, no. 8, pp. 1114–1116.
[33] Smetana, P., Schmidt, A., Zabel, M., et al. (2011). Assessment of repolarization heterogeneity for prediction of mortality in cardiovascular disease: Peak to the end of the T wave interval and nondipolar repolarization components. Journal of Electrocardiology, vol. 44, no. 3, pp. 301–308.
[34] Maury, P., Sacher, F., Gourraud, J. B., et al. (2015). Increased Tpeak-Tend interval is highly and independently related to arrhythmic events in Brugada syndrome. Heart Rhythm, vol. 12, no. 12, pp. 2469–2476.
[35] Karaman, K., Altunkaş, F., Çetin, M., et al. (2015). New markers for ventricular repolarization in coronary slow flow: Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio. Annals of Noninvasive Electrocardiology, vol. 20, no. 4, pp. 338–344.
[36] Mugnai, G., Hunuk, B., Hernandez-Ojeda, J., et al. (2017). Role of electrocardiographic Tpeak-Tend for the prediction of ventricular arrhythmic events in the Brugada syndrome. The American Journal of Cardiology, vol. 120, no. 8, pp. 1332–1337.
[37] Banker, J., Dizon, J., and Reiffel, J. (1997). Effects of the ventriküler activation sequence on the JT interval. The American Journal of Cardiology, vol. 79, no. 6, pp. 816–819.
[38] Inanir, M., Sincer, I., Erdal, E., et al. (2019). Evaluation of electrocardiographic ventricular repolarization parameters in extreme obesity. Journal of Electrocardiology, vol. 53, pp. 36–39.
[39] El-Eraky, H. and Thomas, S. H. (2003). Effects of sex on the pharmacokinetic and pharmacodynamic properties of quinidine. British Journal of Clinical Pharmacology, vol. 56, no. 2, pp. 198–204.
[40] Chan, S., Motonaga, K., Hollander, S., et al. (2016). Electrocardiographic repolarization abnormalities and increased risk of life-threatening arrhythmias in children with dilated cardiomyopathy. Heart Rhythm, vol. 13, no. 6, pp. 1289–1296.
[41] Das, B. B. and Sharma, J. (2004). Repolarization abnormalities in children with a structurally normal heart and ventricular ectopy. Pediatric Cardiology, vol. 25, no. 4, pp. 354–356.
[42] Nigro, G., Russo, V., Di Salvo, G., et al. (2010). Increased heterogenity of ventricular repolarization in obese nonhypertensive children. Pacing and Clinical Electrophysiology, vol. 33, no. 12, pp. 1533–1539.
[43] Kannel, W. B., Plehn, J. F., and Cupples, L. A. (1988). Cardiac failure and sudden death in the Framingham Study. American Heart Journal, vol. 115, no. 4, pp. 869–875.