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

Complications
Severe Hypoglycemia and Cardiovascular or All-Cause Mortality in Patients with Type 2 Diabetes: Seon-Ah Cha, Jae-Seung Yun, Tae-Seok Lim, Seawon Hwang, Eun-Jung Yim, Ki-Ho Song, Ki-Dong Yoo, Yong-Moon Park, Yu-Bae Ahn, Seung-Hyun Ko; Diabetes Metab J. 2016;40(3):202-210. Published online April 5, 2016; DOI: https://doi.org/10.4093/dmj.2016.40.3.202

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Abstract PDF PubReader

Background

We investigated the association between severe hypoglycemia (SH) and the risk of cardiovascular (CV) or all-cause mortality in patients with type 2 diabetes.

Methods

The study included 1,260 patients aged 25 to 75 years with type 2 diabetes from the Vincent Type 2 Diabetes Resgistry (VDR), who consecutively enrolled (n=1,260) from January 2000 to December 2010 and were followed up until May 2015 with a median follow-up time of 10.4 years. Primary outcomes were death from any cause or CV death. We investigated the association between the CV or all-cause mortality and various covariates using Cox proportional hazards regression analysis.

Results

Among the 906 participants (71.9%) who completed follow-up, 85 patients (9.4%) had at least one episode of SH, and 86 patients (9.5%) died (9.1 per 1,000 patient-years). Patients who had died were older, had a longer duration of diabetes and hypertension, received more insulin, and had more diabetic microvascular complications at baseline, as compared with surviving patients. The experience of SH was significantly associated with an increased risk of all-cause mortality (hazard ratio [HR], 2.64; 95% confidence interval [CI], 1.39 to 5.02; P=0.003) and CV mortality (HR, 6.34; 95% CI, 2.02 to 19.87; P=0.002) after adjusting for sex, age, diabetic duration, hypertension, mean glycosylated hemoglobin levels, diabetic nephropathy, lipid profiles, and insulin use.

Conclusion

We found a strong association between SH and increased risk of all-cause and CV mortality in patients with type 2 diabetes.

Citations

Citations to this article as recorded by

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Complications
Cardiovascular Disease Predicts Severe Hypoglycemia in Patients with Type 2 Diabetes: Jae-Seung Yun, Seung-Hyun Ko, Sun-Hye Ko, Ki-Ho Song, Ki-Dong Yoo, Kun-Ho Yoon, Yong-Moon Park, Yu-Bae Ahn; Diabetes Metab J. 2015;39(6):498-506. Published online July 8, 2015; DOI: https://doi.org/10.4093/dmj.2015.39.6.498

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44 Download
22 Web of Science
21 Crossref

Abstract PDF PubReader

Background

To investigate whether a history of prior cardiovascular disease (CVD) is associated with severe hypoglycemia (SH) in patients with type 2 diabetes.

Methods

We conducted a prospective cohort study from January 2001 to December 2012 with a median follow-up time of 9.5 years (5,814 person-years). Patients aged 25 to 75 years with type 2 diabetes and without chronic kidney disease were enrolled (n=894), and 624 patients completed follow-up. SH was defined as hypoglycemic episodes requiring hospitalization or medical care in an emergency department. We used the Cox proportional hazards regression analysis to test associations between SH episodes and potential explanatory variables.

Results

Among the 624 participants who completed follow-up, 60 patients (9.6%) had previous CVD. Compared to patients without CVD, patients with previous CVD were older, had a longer duration of diabetes and hypertension, received more insulin, and had more diabetic microvascular complications at baseline. During follow-up, 62 patients (9.9%) experienced at least one SH episode (incidence of 1.33 per 100 patient-years). The development of SH was associated with a history of CVD (hazard ratio, 1.99; 95% confidence interval, 1.07 to 3.72; P=0.031) after adjusting for sex, age, diabetic duration, hypertension, hemoglobin A1c levels, diabetic complications, cardiovascular autonomic neuropathy, and insulin use.

Conclusion

A history of CVD was an independent risk factor for the development of SH in patients with type 2 diabetes mellitus. For patients with CVD, modulation of glycemic targets and diabetic education for the prevention of hypoglycemia should be implemented.

Citations

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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

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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
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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
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Thomas Forst, Peter Bramlage
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Increasing Trend in the Number of Severe Hypoglycemia Patients in Korea: Jin Taek Kim, Tae Jung Oh, Ye An Lee, Jun Ho Bae, Hyo Jeong Kim, Hye Seung Jung, Young Min Cho, Kyong Soo Park, Soo Lim, Hak Chul Jang, Hong Kyu Lee; Diabetes Metab J. 2011;35(2):166-172. Published online April 30, 2011; DOI: https://doi.org/10.4093/dmj.2011.35.2.166

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30 Crossref

Abstract PDF PubReader

Background

To investigate whether the number of subjects with severe hypoglycemia who are brought to a hospital emergency department is increasing and to identify whether there have been changes in the demographic and clinical characteristics of those subjects.

Methods

We analyzed data from the Emergency Departments of two general hospitals in Seoul, Korea. We included data from all adult subjects with type 2 diabetes who presented to an emergency department with severe hypoglycemia between January 1, 2004 and December 30, 2009.

Results

A total of 740 cases of severe hypoglycemia were identified. The mean subject age was 69±12 years, mean duration of diabetes was 13.8±9.3 years, and 53.2% of subjects were receiving insulin therapy. We observed a sharp rise in the number of cases between 2006 and 2007. Stages 3-5 chronic kidney disease was diagnosed in 31.5% of subjects, and low C-peptide levels (<0.6 ng/mL) were found in 25.5%. The mean subject age, duration of diabetes, HbA1c level, and renal and insulin secretory function values did not change significantly during the study period. The proportion of glimepiride use increased, while use of gliclazide decreased among sulfonylurea users. Use of insulin analogues increased, while use of NPH/RI decreased among insulin users.

Conclusion

We identified a sharp increase in the number of subjects with severe hypoglycemia presenting to an emergency room since 2006. The clinical characteristics of these subjects did not change markedly during the study period. Nationwide studies are warranted to further clarify this epidemic of severe hypoglycemia.

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