Association of hypoglycaemia and risk of cardiac arrhythmia in patients with diabetes mellitus: a systematic review and meta-analysis
Open accessAbstract
Aims: Hypoglycaemia is associated with increased cardiovascular risk among individuals with diabetes mellitus. It has been hypothesized that hypoglycaemia may trigger autonomic changes leading to increased cardiac arrhythmia risk. We conducted a systematic review and meta‐analysis to explore this association. Materials and methods: Ovid Medline, Embase, Scopus, Web of Science and Cochrane were searched from inception to October 10, 2017. We included studies of adults with diabetes (Type 1 or Type 2) that compared acute electrocardiogram (ECG) changes during episodes of hypoglycaemia and euglycaemia. Results: Our search resulted in 4625 citations, among which 20 studies met the predefined inclusion criteria. Finally, 12 studies were included in the descriptive analysis and 15 in the meta‐analysis. Overall hypoglycaemia was associated with a reduction in heart rate variability and an increase in arrhythmia occurrence. QTc interval length was more significantly prolonged during hypoglycaemia compared to euglycaemia (pooled mean difference [95% confidence intervals] [0.64 (0.27‐1.01], P = ·001). Subgroup analysis based on diabetes type showed that QTc prolongation occurred in individuals with Type 1 and Type 2 diabetes; however, the change between euglycaemia reached statistical significance only among individuals with Type 1 diabetes. Conclusion: Our findings suggest that hypoglycaemia results in ECG alterations that are associated with increased risk of cardiac arrhythmia, which is associated with increased cardiovascular events and mortality. More clinical studies are needed to determine the cardiac risks of hypoglycaemia in individuals with diabetes, especially in Type 2 diabetes.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Hypoglycemia is a reported cause of increased QTc in healthy adults and individuals with diabetes.
“Hypoglycemia is a reported cause of an increase in QTc in healthy adults and individuals with diabetes (7–11, 15).”
From Effect of Hypoglycemia on QT Interval in Individuals With and Without Type 2 Diabetes: A Randomized Crossover Trial (2025) · cites this paper as [15]
The Results (Accepted Article; page unavailable) report that hypoglycaemia was associated with significant QTc prolongation compared with euglycaemia in the pooled studies. The Materials and Methods specify that the review included adults with diabetes and extracted only their data when studies also included people without diabetes. Thus this source supports the claim for people with diabetes, but not its extension to healthy adults or a definitive causal interpretation. (LLM, conf=0.90)
Experimental — accuracy not yet measuredA recent meta-analysis did not demonstrate a significant association between QTc prolongation and hypoglycemia in type 2 diabetes.
“a recent meta-analysis examining this relationship in patients with type 1 and type 2 diabetes did not demonstrate a significant association between QTc prolongation and hypoglycemia in type 2 diabetes (15).”
From Effect of Hypoglycemia on QT Interval in Individuals With and Without Type 2 Diabetes: A Randomized Crossover Trial (2025) · cites this paper as [15]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA statement
Moher, D., Liberati, A., Tetzlaff, J., Altman, D. G., & for the PRISMA Group (2009) · BMJ · doi:10.1136/bmj.b2535 · Cited by 83,823 · see citing works
Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement
Moher, D., Liberati, A., Tetzlaff, J., Altman, D. G., & The PRISMA Group (2009) · PLoS Medicine · doi:10.1371/journal.pmed.1000097 · Cited by 64,042 · see citing works
Measuring inconsistency in meta-analyses
Higgins, J. P. T., Thompson, S. G., Deeks, J. J., & Altman, D. G. (2003) · BMJ · doi:10.1136/bmj.327.7414.557 · Cited by 63,139 · see citing works
Quantifying heterogeneity in a meta‐analysis
Higgins, J. P. T., & Thompson, S. G. (2002) · Statistics in Medicine · doi:10.1002/sim.1186 · Cited by 36,763 · see citing works
Stroup, D. F. (2000) · JAMA · doi:10.1001/jama.283.15.2008 · Cited by 20,623 · see citing works
Estimating the mean and variance from the median, range, and the size of a sample
Hozo, S. P., Djulbegovic, B., & Hozo, I. (2005) · BMC Medical Research Methodology · doi:10.1186/1471-2288-5-13 · Cited by 9,062 · see citing works
Effects of Intensive Glucose Lowering in Type 2 Diabetes
(2008) · New England Journal of Medicine · doi:10.1056/nejmoa0802743 · Cited by 7,888 · see citing works
Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes
(2008) · New England Journal of Medicine · doi:10.1056/nejmoa0802987 · Cited by 7,397 · see citing works
Cochrane Handbook for Systematic Reviews of Interventions
Tarsilla, M. (2010) · Journal of MultiDisciplinary Evaluation · doi:10.56645/jmde.v6i14.284 · Cited by 5,228 · see citing works
Glucose control and vascular complications in veterans with type 2 diabetes
Duckworth, W., Abraira, C., Moritz, T., Reda, D., Emanuele, N., Reaven, P. D., Zieve, F. J., Marks, J., Davis, S. N., Hayward, R., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0808431 · Cited by 4,762 · see citing works
Leon, B. M. (2015) · World Journal of Diabetes · doi:10.4239/wjd.v6.i13.1246 · Cited by 1,215 · see citing works
Boussageon, R., Bejan-Angoulvant, T., Saadatian-Elahi, M., Lafont, S., Bergeonneau, C., Kassai, B., Erpeldinger, S., Wright, J. M., Gueyffier, F., & Cornu, C. (2011) · BMJ · doi:10.1136/bmj.d4169 · Cited by 803 · see citing works
International Hypoglycaemia Study Group (2017) · Diabetes Care · doi:10.2337/dc16-2215 · Cited by 608 · see citing works
Goto, A., Arah, O. A., Goto, M., Terauchi, Y., & Noda, M. (2013) · BMJ · doi:10.1136/bmj.f4533 · Cited by 492 · see citing works
Malík, M., Färbom, P., Batchvarov, V., Hnatkova, K., & Camm, A. J. (2002) · Heart · doi:10.1136/heart.87.3.220 · Cited by 437 · see citing works
Chow, E., Bernjak, A., Williams, S., Fawdry, R. A., Hibbert, S., Freeman, J., Sheridan, P. J., & Heller, S. R. (2014) · Diabetes · doi:10.2337/db13-0468 · Cited by 403 · see citing works
Rate-corrected QT interval: Techniques and limitations
Funck‐Brentano, C., & Jaillon, P. (1993) · The American Journal of Cardiology · doi:10.1016/0002-9149(93)90035-b · Cited by 401 · see citing works
Acute and chronic complications of type 2 diabetes mellitus in children and adolescents
Pinhas‐Hamiel, O., & Zeitler, P. S. (2007) · The Lancet · doi:10.1016/s0140-6736(07)60821-6 · Cited by 386 · see citing works
Hypoglycemia and cardiovascular risks
Frier, B. M., Schernthaner, G., & Heller, S. R. (2011) · Diabetes Care · doi:10.2337/dc11-s220 · Cited by 381 · see citing works
Unexplained Deaths of Type 1 Diabetic Patients
Tattersall, R. B., & Gill, G. V. (1991) · Diabetic Medicine · doi:10.1111/j.1464-5491.1991.tb01516.x · Cited by 308 · see citing works
Gill, G. V., Woodward, A., Casson, I. F., & Weston, P. J. (2008) · Diabetologia · doi:10.1007/s00125-008-1177-7 · Cited by 296 · see citing works
Intensive Blood Glucose Control and Vascular Outcomes in Patients with Type 2 Diabetes
Moneta, G. L. (2009) · Yearbook of Vascular Surgery · doi:10.1016/s0749-4041(08)79023-7 · Cited by 242 · see citing works
Weiss, J. N., Chen, P., Qu, Z., et al. (2000) · Circulation Research · doi:10.1161/01.res.87.12.1103 · Cited by 218 · see citing works
Ng, G. A., Brack, K. E., Patel, V. C., & Coote, J. H. (2006) · Cardiovascular Research · doi:10.1016/j.cardiores.2006.12.001 · Cited by 203 · see citing works
Self-citationProlonged QTc interval predicts mortality in patients with Type 1 diabetes mellitus
Rossing, P. R., Breum, L., Major‐Pedersen, A., et al. (2001) · Diabetic Medicine · doi:10.1046/j.1464-5491.2001.00446.x · Cited by 172 · see citing works
Incidence of Coronary Heart Disease in Type 2 Diabetic Men and Women
Avogaro, A., Giorda, C. B., Maggini, M., Mannucci, E., Raschetti, R., Lombardo, F. L., Alegiani, S. S., Turco, S., Velussi, M., & Ferrannini, E. (2007) · Diabetes Care · doi:10.2337/dc06-2558 · Cited by 169 · see citing works
Hypoglycemia, Diabetes, and Cardiovascular Disease
Snell‐Bergeon, J. K., & Wadwa, R. P. (2012) · Diabetes Technology & Therapeutics · doi:10.1089/dia.2012.0031 · Cited by 163 · see citing works
DEVOTE 3: temporal relationships between severe hypoglycaemia, cardiovascular outcomes and mortality
on behalf of the DEVOTE Study Group, Pieber, T. R., Marso, S. P., McGuire, D. K., Zinman, B., Poulter, N. R., Emerson, S. S., Pratley, R. E., Woo, V. C., Heller, S. R., et al. (2017) · Diabetologia · doi:10.1007/s00125-017-4422-0 · Cited by 150 · see citing works
Increased QT dispersion during hypoglycaemia in patients with type 2 diabetes mellitus
Landstedt‐Hallin, L., Englund, A., Adamson, U., & Lins, P. ‐. (1999) · Journal of Internal Medicine · doi:10.1046/j.1365-2796.1999.00528.x · Cited by 141 · see citing works
Hypoglycaemia and Cardiac Arrhythmias in Patients with Type 2 Diabetes Mellitus
Lindström, T., Jorfeldt, L., Tegler, L., & Arnqvist, H. J. (1992) · Diabetic Medicine · doi:10.1111/j.1464-5491.1992.tb01834.x · Cited by 113 · see citing works
Novodvorsky, P., Bernjak, A., Chow, E., Iqbal, A., Sellors, L., Williams, S., Fawdry, R. A., Parekh, B., Jacques, R. M., Marques, J. L. B., et al. (2017) · Diabetes Care · doi:10.2337/dc16-2177 · Cited by 111 · see citing works
Dead-in-bed syndrome in young diabetic patients.
Søvik, O., & Thordarson, H. B. (1999) · PubMed · Cited by 97 · see citing works
Effects of controlled hypoglycaemia on cardiac repolarisation in patients with type 1 diabetes
Koivikko, M. L., Karsikas, M., Salmela, P. I., Tapanainen, J. S., Ruokonen, A., Seppänen, T., Huikuri, H. V., & Perkiömäki, J. S. (2008) · Diabetologia · doi:10.1007/s00125-007-0902-y · Cited by 89 · see citing works
Influence of Autonomic Neuropathy on QTc Interval Lengthening During Hypoglycemia in Type 1 Diabetes
Lee, S. P., Yeoh, L., Harris, N. D., Davies, C. M., Robinson, R. T. C. E., Leathard, A. D., Newman, C. M. H., Macdonald, I. A., & Heller, S. R. (2004) · Diabetes · doi:10.2337/diabetes.53.6.1535 · Cited by 85 · see citing works
Chow, E., Bernjak, A., Walkinshaw, E., Lubina-Solomon, A., Freeman, J., Macdonald, I. A., Sheridan, P. J., & Heller, S. R. (2017) · Diabetes · doi:10.2337/db16-1310 · Cited by 63 · see citing works
Christensen, T. F., Tarnow, L., Randløv, J., Kristensen, L. E., Struijk, J. J., Eldrup, E., & Hejlesen, O. K. (2010) · Diabetologia · doi:10.1007/s00125-010-1802-0 · Cited by 61 · see citing works
Tu, E., Twigg, S. M., Duflou, J. A., & Semsarian, C. (2008) · The Medical Journal of Australia · doi:10.5694/j.1326-5377.2008.tb01849.x · Cited by 60 · see citing works
Koivikko, M. L., Salmela, P. I., Airaksinen, J. K. E., Tapanainen, J. S., Ruokonen, A., Mäkikallio, T. H., & Huikuri, H. V. (2005) · Diabetes · doi:10.2337/diabetes.54.3.744 · Cited by 59 · see citing works
Whitsel, E. A., Boyko, E. J., Rautaharju, P. M., et al. (2005) · Diabetes Care · doi:10.2337/diacare.28.8.2045 · Cited by 57 · see citing works
Koivikko, M. L., Tulppo, M. P., Kiviniemi, A. M., Kallio, M., Perkiömäki, J. S., Salmela, P. I., Airaksinen, J. K. E., & Huikuri, H. V. (2012) · Diabetes Care · doi:10.2337/dc11-2120 · Cited by 46 · see citing works
Cardiac Effects of Sulfonylurea-Related Hypoglycemia
Middleton, T. L., Wong, J., Molyneaux, L. M., Brooks, B. A., Yue, D. K., Twigg, S. M., & Wu, T. (2017) · Diabetes Care · doi:10.2337/dc16-1972 · Cited by 40 · see citing works
Lipponen, J. A., Kemppainen, J., Karjalainen, P. A., Laitinen, T. P., Mikola, H., Kärki, T., & Tarvainen, M. P. (2011) · Physiological Measurement · doi:10.1088/0967-3334/32/6/003 · Cited by 30 · see citing works
Nicolson, W. B., McCann, G. P., Smith, M. I., Sandilands, A., Stafford, P. J., Schlindwein, F. S., Samani, N. J., & Ng, G. A. (2014) · Heart · doi:10.1136/heartjnl-2014-305672 · Cited by 29 · see citing works
Self-citationAutonomic control during acute hypoglycemia in type 1 diabetes mellitus
Limberg, J. K., Farni, K. E., Taylor, J. L., Dube, S., Basu, A., Basu, R., Wehrwein, E. A., & Joyner, M. J. (2014) · Clinical Autonomic Research · doi:10.1007/s10286-014-0253-y · Cited by 27 · see citing works
Christensen, T. F., Cichosz, S. L., Tarnow, L., Randløv, J., Kristensen, L. E., Struijk, J. J., Eldrup, E., & Hejlesen, O. K. (2014) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2014.03.007 · Cited by 25 · see citing works
Soydan, N., Bretzel, R. G., Fischer, B., Wagenlehner, F. R. A., Pilatz, A. M. E., & Linn, T. (2013) · Metabolism · doi:10.1016/j.metabol.2012.12.003 · Cited by 25 · see citing works
Lee, A. S., Brooks, B. A., Simmons, L., Kilborn, M. J., Wong, J., Twigg, S. M., & Yue, D. K. (2016) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2016.01.005 · Cited by 21 · see citing works
QT Measurement and Heart Rate Correction during Hypoglycemia: Is There a Bias?
Christensen, T. F., Randløv, J., Kristensen, L. E., Eldrup, E., Hejlesen, O. K., & Struijk, J. J. (2010) · Cardiology Research and Practice · doi:10.4061/2010/961290 · Cited by 20 · see citing works
Due-Andersen, R., Høi-Hansen, T., Larroudé, C. E., et al. (2008) · EP Europace · doi:10.1093/europace/eun137 · Cited by 15 · see citing works
Koivikko, M. L., Kenttä, T. V., Salmela, P. I., Huikuri, H. V., & Perkiömäki, J. S. (2016) · Acta Diabetologica · doi:10.1007/s00592-016-0941-2 · Cited by 15 · see citing works
Cichosz, S. L., Frystyk, J., Tarnow, L., & Fleischer, J. (2017) · Diabetes Technology & Therapeutics · doi:10.1089/dia.2016.0342 · Cited by 13 · see citing works
Induction in C57BL/KsJ Mice of Complement-dependent Antibody Cytotoxic to Cultured Beta Cells
Leiter, E. H., Simon, D. M., Cherry, M., et al. (1981) · Diabetes · doi:10.2337/diab.30.1.30 · Cited by 11 · see citing works
Færch, L. H., Thorsteinsson, B., Tarnow, L., Holst, J. J., Kjær, T., Kanters, J., Larroude, C., Dela, F., & Pedersen-Bjergaard, U. (2015) · Journal of the Renin-Angiotensin-Aldosterone System · doi:10.1177/1470320314529356 · Cited by 8 · see citing works
QT interval prolongation during rapid fall in blood glucose in type I diabetes
Christensen, T. F., Lewinsky, I., Kristensen, L. E., et al. (2007) · Computers in cardiology · doi:10.1109/cic.2007.4745492 · Cited by 8 · see citing works
Rozkovec, A., Rowlands, E., Singh, D., et al. (1982) · Circulation · doi:10.1161/01.cir.66.5.1137 · Cited by 4 · see citing works
[Electrocardiographic changes in insulin induced hypoglycemia].
Montero, J. M., Camacho, I., Martí, M. P., et al. (1979) · PubMed · Cited by 4 · see citing works
Brown, M. R., Javorsky, G., & Platts, D. G. (2010) · Cardiology Research and Practice · doi:10.4061/2010/750874 · Cited by 2 · see citing works
Chanson, P., & Pariente, A. E. (2014) · PubMed · Cited by 1 · see citing works
Marques (1997) · doi:10.1002/(sici)1096-9136(199708)14:8
Flagged first, then by citations
Research works printed but not linked: 4
- [15]15. Stroup DF, Berlin JA, Morton SC, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. JAMA. 2000; 283: 2008-2012
- [20]20. Bazett H. An analysis of the time-relations of electrocardiograms. Heart. 1920; 7: 353-370
- [54]54. Stiefelhagen P. Underestimated risk for type 2 diabetic patients: Mortal danger due to hypoglycemias! MMW-Fortschr Med. 2010; 152: 12
- [55]55. Struchkova YV, Strongin LG, Pochinka IG, Konysheva MS. Combined monitoring (ECG-MT and CGMS) in the study of arrhythmogenic factors in patients with diabetes mellitus type 2 suffering from chronic cardiac failure. Sovrem Tehnol Med. 2011; 2011: 85-89
Cited by
Sorted by citations
Mattishent, K., & Loke, Y. K. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.571568 · Cited by 69 · see citing works
Fitchett, D., Inzucchi, S. E., Wanner, C., Mattheus, M., George, J. T., Vedin, O., Zinman, B., & Johansen, O. E. (2020) · European Heart Journal · doi:10.1093/eurheartj/ehz621 · Cited by 34 · see citing works
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
- Fitzpatrick, C., Chatterjee, S., Seidu, S., Bodicoat, D. H., Ng, G. A., Davies, M. J., & Khunti, K.
- Affiliations
- University of Leicester (GB)
- Leicester General Hospital (GB)
- Department of Cardiovascular Sciences University of Leicester Leicester UK
- Corresponding author
- Khunti, Kamlesh
- ORCID
- Venue
- Diabetes, Obesity and Metabolism
- Publisher
- Wiley
- Published
- 2018-05-31
- Volume
- 20
- Issue
- 9
- Pages
- 2169-2178
- ISSN
- 1462-8902 (ISSN-L)
- 1463-1326
- OpenAlex
- W2799453671
- Cited by
- 57
- References
- 59
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 3 · 2023: 10 · 2022: 7 · 2021: 8 · 2020: 8 · 2019: 8 · 2018: 2
- FWCI
- 1.00
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes Obesity and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Figshare (submittedVersion, cc-by)
- Minerva Access (University of Melbourne) (submittedVersion)
- Leicester Research Archive (University of Leicester) (submittedVersion, other-oa)
- Funders
- University Hospitals of Leicester NHS Trust
- Loughborough University
- University of Leicester
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- hypoglycemia, cardiac arrhythmias, diabetes mellitus, type 1 diabetes, type 2 diabetes, QTc prolongation, heart rate variability, electrocardiographic changes, autonomic dysfunction, cardiovascular risk
- MeSH terms
- Adult, Aged, Arrhythmias, Cardiac, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Electrocardiography, Female, Heart Rate, Humans, Hypoglycemia, Male, Middle Aged, Risk Factors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
