Diabetes & Metabolism Journal

Original Articles

Complications
Baseline-Corrected QT (QTc) Interval Is Associated with Prolongation of QTc during Severe Hypoglycemia in Patients with Type 2 Diabetes Mellitus: Seon-Ah Cha, Jae-Seung Yun, Tae-Seok Lim, Yoon-Goo Kang, Kang-Min Lee, Ki-Ho Song, Ki-Dong Yoo, Yong-Moon Park, Seung-Hyun Ko, Yu-Bae Ahn; Diabetes Metab J. 2016;40(6):463-472. Published online October 5, 2016; DOI: https://doi.org/10.4093/dmj.2016.40.6.463

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Background

We investigated an association between baseline heart rate-corrected QT (QTc) interval before severe hypoglycemia (SH) and prolongation of QTc interval during SH in patients with type 2 diabetes mellitus (T2DM).

Methods

Between January 2004 and June 2014, 208 patients with T2DM, who visited the emergency department because of SH and underwent standard 12-lead electrocardiography within the 6-month period before SH were consecutively enrolled. The QTc interval was analyzed during the incidence of SH, and 6 months before and after SH. QTc intervals of 450 ms or longer in men and 460 ms or longer in women were considered abnormally prolonged.

Results

The mean age and diabetes duration were 68.1±12.1 and 14.1±10.1 years, respectively. The mean QTc intervals at baseline and SH episodes were 433±33 and 460±33 ms, respectively (P<0.001). One hundred and fourteen patients (54.8%) had a prolonged QTc interval during SH. There was a significant decrease in the prolonged QTc interval within 6 months after SH (QTc interval prolongation during SH vs. after recovery, 54.8% vs. 33.8%, P<0.001). The prolonged QTc interval was significantly associated with baseline QTc interval prolongation (odds ratio, 2.92; 95% confidence interval, 1.22 to 6.96; P=0.016) after adjusting for multiple confounders.

Conclusion

A prolonged QTc interval at baseline was significantly associated with prolongation of the QTc interval during SH in patients with T2DM, suggesting the necessity of QTc interval monitoring and attention to those with a prolonged QTc interval to prevent SH.

Citations

Citations to this article as recorded by

Prevalence of QT prolongation and its risk factors in patients with type 2 diabetes
Khaled Aburisheh, Mohammad F. AlKheraiji, Saleh I. Alwalan, Arthur C. Isnani, Mohamed Rafiullah, Muhammad Mujammami, Assim A. Alfadda
BMC Endocrine Disorders.2023;[Epub] CrossRef
U-shaped association between the triglyceride–glucose index and atrial fibrillation incidence in a general population without known cardiovascular disease
Xiao Liu, Ayiguli Abudukeremu, Yuan Jiang, Zhengyu Cao, Maoxiong Wu, Jianyong Ma, Runlu Sun, Wanbing He, Zhiteng Chen, Yangxin Chen, Peng Yu, Wengen Zhu, Yuling Zhang, Jingfeng Wang
Cardiovascular Diabetology.2023;[Epub] CrossRef
Celebrities in the heart, strangers in the pancreatic beta cell: Voltage‐gated potassium channels Kv7.1 and Kv11.1 bridge long QT syndrome with hyperinsulinaemia as well as type 2 diabetes
Anniek F. Lubberding, Christian R. Juhl, Emil Z. Skovhøj, Jørgen K. Kanters, Thomas Mandrup‐Poulsen, Signe S. Torekov
Acta Physiologica.2022;[Epub] CrossRef
Severe hypoglycemia as a risk factor for cardiovascular outcomes in patients with type 2 diabetes: is it preventable?
Seung-Hyun Ko
Cardiovascular Prevention and Pharmacotherapy.2022; 4(3): 106. CrossRef
Heart rate-corrected QT interval prolongation is associated with decreased heart rate variability in patients with type 2 diabetes
Seon-Ah Cha
Medicine.2022; 101(45): e31511. CrossRef
Severe hypoglycemia as a preventable risk factor for cardiovascular disease in patients with type 2 diabetes mellitus
Soo-Yeon Choi, Seung-Hyun Ko
The Korean Journal of Internal Medicine.2021; 36(2): 263. CrossRef
Review of the cardiovascular safety of dipeptidyl peptidase-4 inhibitors and the clinical relevance of the CAROLINA trial
Marile Santamarina, Curt J. Carlson
BMC Cardiovascular Disorders.2019;[Epub] CrossRef
Antioxidant effects of epigallocatechin-3-gallate on the aTC1-6 pancreatic alpha cell line
Ting Cao, Xiong Zhang, Dan Yang, Yue-Qian Wang, Zheng-Dong Qiao, Jian-Ming Huang, Peng Zhang
Biochemical and Biophysical Research Communications.2018; 495(1): 693. CrossRef
Severe hypoglycemia is a risk factor for atrial fibrillation in type 2 diabetes mellitus: Nationwide population-based cohort study
Seung-Hyun Ko, Yong-Moon Park, Jae-Seung Yun, Seon-Ah Cha, Eue-Keun Choi, Kyungdo Han, Eugene Han, Yong-ho Lee, Yu-Bae Ahn
Journal of Diabetes and its Complications.2018; 32(2): 157. CrossRef
Incidence of prolonged QTc and severe hypoglycemia in type 1 diabetes: the EURODIAB Prospective Complications Study
Cristina Amione, Sara Giunti, Paolo Fornengo, Sabita S. Soedamah-Muthu, Nish Chaturvedi, J. H. Fuller, Federica Barutta, Gabriella Gruden, Graziella Bruno
Acta Diabetologica.2017; 54(9): 871. CrossRef

Corrected QT Interval Prolongation during Severe Hypoglycemia without Hypokalemia in Patients with Type 2 Diabetes: Jae Won Beom, Jung Min Kim, Eun Joo Chung, Ju Yeong Kim, Seung Yeong Ko, Sang Don Na, Cheol Hwan Kim, Gun Park, Mi Yeon Kang; Diabetes Metab J. 2013;37(3):190-195. Published online June 14, 2013; DOI: https://doi.org/10.4093/dmj.2013.37.3.190

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Abstract PDF PubReader

Background

To evaluate the effects of severe hypoglycemia without hypokalemia on the electrocardiogram in patients with type 2 diabetes in real-life conditions.

Methods

Electrocardiograms of adult type 2 diabetic patients during the episodes of severe hypoglycemia and the recovered stage were obtained and analysed between October 1, 2011 and May 31, 2012. Patients who maintained the normal serum sodium and potassium levels during the episodes of severe hypoglycemia were only selected as the subjects of this study. Severe hypoglycemia was defined, in this study, as the condition requiring active medical assistance such as administering carbohydrate when serum glucose level was less than 60 mg/dL.

Results

Nine type 2 diabetes patients (seven men, two women) were included in the study. The mean subject age was 73.2±7.7 years. The mean hemoglobin A1c level was 6.07%±1.19%. The median duration of diabetes was 10 years (range, 3.5 to 30 years). Corrected QT (QTc) intervals were significantly increased during the episodes of severe hypoglycemia compared to the recovered stage (447.6±18.2 ms vs. 417.2±30.6 ms; P<0.05). However, the morphology and the amplitude of the T waves were not changed and ST-segment elevation and/or depression were not found during the episodes of severe hypoglycemia.

Conclusion

In this study, QTc interval prolongation during the episodes of severe hypoglycemia was observed without hypokalemia. Therefore, the distinct alterations in cardiac repolarization during the episodes of severe hypoglycemia may not be associated with hypokalemia.

Citations

Citations to this article as recorded by

Prevalence of QT prolongation and its risk factors in patients with type 2 diabetes
Khaled Aburisheh, Mohammad F. AlKheraiji, Saleh I. Alwalan, Arthur C. Isnani, Mohamed Rafiullah, Muhammad Mujammami, Assim A. Alfadda
BMC Endocrine Disorders.2023;[Epub] CrossRef
Celebrities in the heart, strangers in the pancreatic beta cell: Voltage‐gated potassium channels Kv7.1 and Kv11.1 bridge long QT syndrome with hyperinsulinaemia as well as type 2 diabetes
Anniek F. Lubberding, Christian R. Juhl, Emil Z. Skovhøj, Jørgen K. Kanters, Thomas Mandrup‐Poulsen, Signe S. Torekov
Acta Physiologica.2022;[Epub] CrossRef
Severe Hypoglycemia Increases Dementia Risk and Related Mortality: A Nationwide, Population-based Cohort Study
Eugene Han, Kyung-do Han, Byung-Wan Lee, Eun Seok Kang, Bong-Soo Cha, Seung-Hyun Ko, Yong-ho Lee
The Journal of Clinical Endocrinology & Metabolism.2022; 107(5): e1976. CrossRef
CHANGES IN THE QT INTERVAL IN PATIENTS WITH ANKYLOSING SPONDYLITIS
A. Zayaeva, Galina Koshukova, E. Dolya, A. Nikolayeva, D. Ten
Tavricheskiy Mediko-Biologicheskiy Vestnik.2022; 23(4): 20. CrossRef
Cardiac Effects of Sulfonylurea-Related Hypoglycemia
Timothy L. Middleton, Jencia Wong, Lynda Molyneaux, Belinda A. Brooks, Dennis K. Yue, Stephen M. Twigg, Ted Wu
Diabetes Care.2017; 40(5): 663. CrossRef
Major rapid weight loss induces changes in cardiac repolarization
Esben Vedel-Larsen, Eva Winning Iepsen, Julie Lundgren, Claus Graff, Johannes J. Struijk, Torben Hansen, Jens Juul Holst, Sten Madsbad, Signe Torekov, Jørgen K. Kanters
Journal of Electrocardiology.2016; 49(3): 467. CrossRef
Avoiding or coping with severe hypoglycemia in patients with type 2 diabetes
Jae-Seung Yun, Seung-Hyun Ko
The Korean Journal of Internal Medicine.2015; 30(1): 6. CrossRef
Blood electrolyte disturbances during severe hypoglycemia in Korean patients with type 2 diabetes
Mi Yeon Kang
The Korean Journal of Internal Medicine.2015; 30(5): 648. CrossRef
Vildagliptin, a DPP-4 inhibitor for the twice-daily treatment of type 2 diabetes mellitus with or without metformin
Thomas Forst, Peter Bramlage
Expert Opinion on Pharmacotherapy.2014; 15(9): 1299. CrossRef
Does glycemic control reverse dispersion of ventricular repolarization in type 2 diabetes?
Takayuki Miki, Toshiyuki Tobisawa, Tatsuya Sato, Masaya Tanno, Toshiyuki Yano, Hiroshi Akasaka, Atsushi Kuno, Makoto Ogasawara, Hiromichi Murase, Shigeyuki Saitoh, Tetsuji Miura
Cardiovascular Diabetology.2014;[Epub] CrossRef
Hypoglycemia at Admission in Patients With Acute Myocardial Infarction Predicts a Higher 30-Day Mortality in Patients With Poorly Controlled Type 2 Diabetes Than in Well-Controlled Patients
Sang Ah Lee, Suk Ju Cho, Myung Ho Jeong, Young Jo Kim, Chong Jin Kim, Myeong Chan Cho, Hyo-Soo Kim, Youngkeun Ahn, Gwanpyo Koh, Jeong mi Lee, Seok Kyu Oh, Kyeong Ho Yun, Ha Young Kim, Chung Gu Cho, Dae Ho Lee
Diabetes Care.2014; 37(8): 2366. CrossRef

Prolonged QT Interval and the BMI, Systolic BP and HDL-Cholesterol in Type 2 Diabetic Patients.: Chunggu Cho, Hye Jung No, Hyo Jeong Oh, Bong Joon Yang, Ha Young Kim, Byoung Hyun Park; Korean Diabetes J. 2005;29(3):215-222. Published online May 1, 2005

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Abstract PDF: BACKGROUND
A prolonged QT interval is considered as an indicator of an increased risk of coronary heart disease, malignant ventricular arrhythmias and/or sudden death. QT interval prolongation has been reported to be a common finding in patients with obesity and diabetic autonomic neuropathy and it is well known that both leptin and insulin stimulate sympathetic activity. The waist to hip ratio and the plasma insulin levels were recently reported to be correlated with the QT intervals and the sympathovagal balance. The aim of the present study was to evaluate the association of the features of metabolic syndrome and the QT interval in type 2 diabetic patients. METHODS: We studied 114 type 2 diabetes(45 males and 69 females). The QT intervals were measured by a software program and then the QTc was calculated. The fasting glucose, total cholesterol, triglyceride and high-density lipoprotein(HDL)-cholesterol, HbAIC and Cpeptide were measured. All the patients received clinical tests for cardiovascular autonomic dysfunction by the Ewing's method. RESULTS: A significant difference was found in the mean QT interval between the patients with an autonomic score>=1 and the patients who were without cardiac autonomic neuropathy(autonomic score=0). On Pearson's simple regression analysis, the QT interval showed positive correlations with the BMI, fasting C-peptide, systolic blood pressure(sBP), and age. The QT interval also showed negative correlation with the HDL-cholesterol. The associations of the QTc with triglyceride, fasting glucose, and the autonomic score did not reach statistical significance. On the multiple regression analysis, the QT interval was independently correlated with BMI, systolic BP and HDL-cholesterol but not with the other variables that we tested(c-peptide, autonomic score, diastolic blood pressure, glycated hemoglobin, triglyceride and cholesterol). CONCLUSION: Our results suggest that a variety of features of metabolic syndrome are associated with QT interval prolongation in the type 2 diabetic patients

QTc Interval and QT Dispersion Prolongation in NIDDM Patients with Diabetic Autonomic Neuropathy.: Yong Kyun Cho, Seung Won Lee, Won Tae Seo, Yoon Sang Choi, Jin Ho Kang, Man Ho Lee, Sang Jong Lee; Korean Diabetes J. 1998;22(1):93-102. Published online January 1, 2001

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Abstract PDF: BACKGROUND
It has been reported that QTc interval and QT dispersion prolongation on 12 lead EKG reflects predictability and diagnosis of cardiovascular complications induced by autonomic nervous system abnormalities. We have investigated in NIDDM patients whether severity of cadiovascular autonomic neuropathy(CAN) evaluated by conventional standard cardiovascular autonomic function test is correlated with prolongation of QT, QTc interval and QT dispersion. In addition, whether these prolonagtion can reflect CAN and if any other clinical variables related to pralongatian exist. METHODS: Eighty patients(39 male, 41 female) treated with oral hypoglycemic agents or insulin after diagnosis of NIDDM in our hospital were included in the study. These patients were devided into three groups (Group I, 13 subjects: No CAN, Group II, 20 subjects: Borderline CAN, Group III, 47 subjects: Definite CAN) according to the score of standard catdiovascular autonomic function test(Deep breathing test, Lying to standing test, Heart ration on Valsalva manuever, Postural BP drop test). The measured QT, QTc interval and QT disp rsion of eaeh diabetic group and control group were analyzed. RESULTS: l. Statistically significant prolongation of QT,QTc, QT dispersion was observed in NIDDM tients as compared with those of control group(p=0.015, 0,021, 0.001). 2. Severity of autonomic neuropathy has shown positive correlation with only prolongation of QT dispersion(p<0.05) in three diabetic subgroups. 3. Statistically significant difference was not ob::rved in HbAlc and BMI between each patients groups of NIDDM(p>0.05) but both HbAlc and BMI showed weak positive correlation with prologation of QT dispersion(r=0.262, r=0.267 repectively). CONCLUSION: QTc interval and QT dispersion are considered easily accessible factors to predict and evaluate the degree of cardiovascular autonomic function abnormalities in NIDDM patients, yet further long term follow up and study in large group should be carried out to decide if these factor can predict and reflect severity of cardiovascular abnormalities such as ventricular arrhythmia, and sudden cardiac death. In additian, prolonged QT dispersion has shown weak positive correlation with both HbAlc and BMI and some other influential factors are suggested to play a role in autonomic neuropathy in NIDDM patients.

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