Insulin Resistance and Other Comorbidities of Obesity as Independent Variables on Ventricular Repolarization in Children and Adolescents
Keywords:
obesity, insulin resistance, comorbidities, ventricular repolarization, child, adolescence
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.
References
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arrhythmogenesis. Journal of Electrocardiology, vol. 41, no. 6, pp. 567–574.
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arrhythmias and biventricular size and wall mass in tetralogy of Fallot with pulmonary
regurgitation. Heart, vol. 88, no. 5, pp. 515–520.
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type 2 diabetes mellitus. PLoS One, vol. 11, no. 4, pp. 1–13.
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adults: a hospital-based study. Diabetes, Obesity and Metabolism, vol. 5, no. 2, pp.
126–130.
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vol. 373, no. 9669, pp. 1083–1096.
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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.
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 çağ� (7-
8 yaş) şişmanl�k araşt�rmas� (COSI-TUR) 2013. Retrieved from:
https://hsgm.saglik.gov.tr/tr/beslenmehareket-yayinlar1/beslenmehareketkitaplar/270.html
[5] Ozcebe, H., Bosi, A. T. B., Yard�m, M. S., et al. (2017). Türkiye çocukluk çağ�
(İlkokul 2. s�n�f öğrencileri) şişmanl�k araşt�rmas� 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., Maz�c�oğlu, 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.
