Severe hypoglycemia and incidence of QT interval prolongation among adults with type 2 diabetes
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Context: There is a paucity of large-scale epidemiological studies on the link between severe hypoglycemia (SH) and corrected QT (QTc) interval prolongation in type 2 diabetes (T2DM). Objective: To evaluate the association of SH with QTc prolongation in adults with T2DM. Methods: Prospective cohort analysis of participants enrolled in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) study without QTc prolongation at baseline. SH was assessed over a 24-month period. Incident QTc prolongation was ascertained using follow-up electrocardiograms. Modified Poisson regression was used to generate the risk ratio (RR) and 95% CI for QTc prolongation. Results: Among 8277 participants (mean age 62.6 years [SD 6.5], 38.7% women, 62.8% White), 324 had ≥1 SH episode (3.9%). Over a median of 5 years, 517 individuals developed QTc prolongation (6.3%). Participants with SH had a 66% higher risk of QTc prolongation (RR 1.66, 95% CI 1.16-2.38). The incidence of QTc prolongation was 10.3% (27/261) and 14.3% (9/63) for participants with 1 and ≥2 SH, respectively. Compared with no SH, RRs for patients with 1 and ≥2 SH episodes were 1.57 (95% CI 1.04-2.39) and 2.01 (95% CI 1.07-3.78), respectively. Age modified the association of SH with QTc prolongation (PInteraction = .008). The association remained significant among younger participants (<61.9 years [median age]: RR 2.63, 95% CI 1.49-4.64), but was nonsignificant among older participants (≥61.9 years: RR 1.37, 95% CI 0.87-2.17). Conclusion: In a large population with T2DM, SH was associated with an increased risk of QTc prolongation independently of other risk factors such as cardiac autonomic neuropathy. The association was strongest among younger participants.
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A recent prospective analysis of individuals with type 2 diabetes in the ACCORD study showed that those who experienced severe hypoglycemia during 5-year follow-up had a 66% higher risk of QTc prolongation, with risk increasing if they had 2 or more episodes.
“A recent prospective analysis of individuals with type 2 diabetes that were part of the ACCORD study showed that those who had experienced severe hypoglycemia (defined as a blood sugar < 50 mg/dL requiring medical assistance) at any point during a 5 year follow-up had a 66% higher risk of QTc prolonga-ion and the risk increased if an individual had 2 or more episodes of severe hypoglycemia (24).”
From Effect of Hypoglycemia on QT Interval in Individuals With and Without Type 2 Diabetes: A Randomized Crossover Trial (2025) · cites this paper as [24]
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Haas, A. V., Koefoed, A. W., Celli, J., Bonyhay, I., White, J., Meyer, K. M., Easly-Merski, R. M., Heydarpour, M., Adler, G. K., & Freeman, R. (2025) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgae919
- Authors
- Kaze, A. D., Yuyun, M. F., Erqou, S., Fonarow, G. C., & Echouffo-Tcheugui, J. B.
- Affiliations
- Department of Medicine, LifePoint Health , Danville, VA 24541 , USA
- Harvard University (US)
- Brown University (US)
- University of California, Los Angeles (US)
- Johns Hopkins University (US)
- Corresponding author
- Echouffo-Tcheugui, Justin B
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2022-04-09
- Volume
- 107
- Issue
- 7
- Pages
- e2743-e2750
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC9202715
- OpenAlex
- W4223585514
- Cited by
- 18
- References
- 37
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 4 · 2023: 4 · 2022: 4
- FWCI
- 2.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (K23 HL153774)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- severe hypoglycemia, QTc prolongation, type 2 diabetes, cardiac arrhythmias, age as confounder, ACCORD trial, young adults
- MeSH terms
- Adult, Diabetes Mellitus, Type 2, Electrocardiography, Female, Humans, Hypoglycemia, Long QT Syndrome, Male, Middle Aged, Prospective Studies, Risk Factors, Incidence
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