Cited by 175Hyperglycemia and glycemic control in critically ill and hospitalized patientsDiabetes Management and ResearchPatient Safety and Medication Errors

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Hypoglycemia-associated Mortality Is Not Drug-associated but Linked to Comorbidities

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Boucai, Laura, Southern, William N., Zonszein, Joel·2011·The American Journal of Medicine

DOI 10.1016/j.amjmed.2011.07.011PMC PMC3200530

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Abstract

Objective Although tight glucose control is used widely in hospitalized patients, there is concern that medication-induced hypoglycemia may worsen patient outcomes. We sought to determine if the mortality risk associated with hypoglycemia in hospitalized noncritically ill patients is linked to glucose-lowering medications (drug-associated hypoglycemia) or merely an association mediated by comorbidities (spontaneous hypoglycemia).Methods A retrospective cohort of patients admitted to the general wards of an academic center during 2007 was studied. The in-hospital mortality risk of a hypoglycemic group (at least 1 blood glucose ≤ 70 mg/dL) was compared with that of a normoglycemic group using survival analysis. Stratification by subgroups of patients with spontaneous and drug-associated hypoglycemia was performed.Results Among 31,970 patients, 3349 (10.5%) had at least 1 episode of hypoglycemia. Patients with hypoglycemia were older, had more comorbidities, and received more antidiabetic agents. Hypoglycemia was associated with increased in-hospital mortality (hazard ratio [HR], 1.67; 95% confidence interval [CI], 1.33-2.09; P<.001). However, this greater risk was limited to patients with spontaneous hypoglycemia (HR, 2.62; 95% CI, 1.97-3.47; P<.001) and not to patients with drug-associated hypoglycemia (HR, 1.06; 95% CI, 0.74-1.52; P=.749). After adjustment for patient comorbidities, the association between spontaneous hypoglycemia and mortality was eliminated (HR, 1.11; 95% CI, 0.76-1.64; P=.582).Conclusion Drug-associated hypoglycemia was not associated with increased mortality risk in patients admitted to the general wards. The association between spontaneous hypoglycemia and mortality was eliminated after adjustment for comorbidities, suggesting that hypoglycemia may be a marker of disease burden rather than a direct cause of death.

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Empowering hospitalized patients with diabetes: implementation of a hospital-wide CGM policy with EHR-integrated validation for dosing insulin
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Continuous Glucose Monitoring in General Wards for Prevention of Hypoglycemia: Results From the Glucose Telemetry System Pilot Study
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Hypoglycemia as a Driver of Cardiovascular Risk in Diabetes
Moheet, A. A., & Seaquist, E. R. (2013) · Current Atherosclerosis Reports · doi:10.1007/s11883-013-0351-7 · Cited by 30
Association of Inpatient Glucose Measurements With Amputations in Patients Hospitalized With Acute Diabetic Foot
Peled, S., Pollack, R. M., Elishoov, O., Haze, A., & Cahn, A. (2019) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2019-00774 · Cited by 31
Glycemic Control and Cardiovascular Disease: What’s a Doctor to Do?
Kishore, P., Kim, S. H., & Crandall, J. P. (2012) · Current Diabetes Reports · doi:10.1007/s11892-012-0268-5 · Cited by 30
“These finding support the view, also proposed by others [50], that the”
Result
Regular insulin added to total parenteral nutrition vs subcutaneous glargine in non-critically ill diabetic inpatients, a multicenter randomized clinical trial: INSUPAR trial
Olveira, G., Abuín, J., López, R., Herránz, S., García‐Almeida, J. M., García-Malpartida, K., Ferrer, M., Cáncer, E., Pérez, L. M. L., Álvarez, J., et al. (2019) · Clinical Nutrition · doi:10.1016/j.clnu.2019.02.036 · Cited by 30
“Similar to hyperglycemia, hypoglycemia is associated with increased in-hospital mortality but the risk might be limited to patients with spontaneous hypoglycemia and not to patients with drug-associated hypoglycemia [38].”
Background
Incidence and Correlates of Hypoglycemia in Type 2 Diabetes. The Hypos-1 Study
Ozzello, C. B. G. A. (2014) · Journal of Diabetes & Metabolism · doi:10.4172/2155-6156.1000344 · Cited by 27
“The importance of the frailty of the patient is further documented by the association with diabetes complications, increasing age and diabetes duration [27,28].”
Background
Medication-induced and spontaneous hypoglycemia carry the same risk for hospital mortality in critically ill patients
Saliba, L., Cook, C. H., Dungan, K. M., Porter, K. M., & Murphy, C. V. (2016) · Journal of Critical Care · doi:10.1016/j.jcrc.2016.06.010 · Cited by 26
“One study suggests similar mortality in medicationinduced vs spontaneous hypoglycemia, whereas others have suggested that spontaneous hypoglycemia is associated with higher risk for mortality than medication-induced hypoglycemia [10,13,14].”
Background
Inpatient Hypoglycemia: A Challenge That Must Be Addressed
Eiland, L. A., Goldner, W. S., Drincic, A., & Desouza, C. V. (2013) · Current Diabetes Reports · doi:10.1007/s11892-013-0445-1 · Cited by 26
“Additionally, after adjusting for patient comorbidities, no association was found between spontaneous hypoglycemia and mortality [30].”
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The impact of glycaemic variability on the surgical patient
Dhatariya, K., Levy, N., & Hall, G. (2016) · Current Opinion in Anaesthesiology · doi:10.1097/aco.0000000000000326 · Cited by 26
“The risk factors for developing inpatient hypoglycemia include older age, presence of comorbidities, diabetes, increasing number of antidiabetic agents, tight glycaemic control, septic shock, renal insufficiency, mechanical ventilation, and severity of illness [57,58].”
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Long-term insulin glargine therapy in type 2 diabetes mellitus: a focus on cardiovascular outcomes
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Umpierrez, G. E., & Kosiborod, M. (2014) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2014.03.008 · Cited by 21
“Results of several studies have shown that it’s primarily spontaneous (rather than iatrogenic) hypoglycemia that is associated with increased risk of inpatient mortality and complications (Boucai et al., 2011; Gamble, Eurich, Marrie, & Majumdar, 2010; Kosiborod et al., 2009).”
Background
Association of hypoglycaemia with the risks of arrhythmia and mortality in individuals with diabetes - a systematic review and meta-analysis
Li, G., Zhong, S., Wang, X., & Zhuge, F. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1222409 · Cited by 23
“Meanwhile, some studies (25) show that only spontaneous hypoglycaemia is associated with increased mortality, while others (26, 27) show no effect.”
Background
Association Between Intra-Hospital Uncontrolled Glycemia and Health Outcomes in Patients with Diabetes: A Systematic Review of Observational Studies
Carvalho, R. C., Nishi, F. A., Ribeiro, T. B., França, G. G., & Aguiar, P. M. (2020) · Current Diabetes Reviews · doi:10.2174/1573399816666200130093523 · Cited by 20
Hypoglycemia in noncritically ill patients receiving total parenteral nutrition: A multicenter study.
Olveira, G., Tapia, M. J., Ocón, J., Cabrejas-Gómez, C., Ballesteros-Pomar, M. D., Vidal‐Casariego, A., Irigoyen, C. A., Olivares, J., Conde-García, M. D. C., García‐Manzanares, Á., et al. (2014) · Nutrition · doi:10.1016/j.nut.2014.04.023 · Cited by 17
“5%) had at least one episode of hypoglycemia (<70mg/ dL) [28].”
Background
Continuous glucose monitoring (CGM) in a non-Icu hospital setting: The patient's journey
Irace, C., Coluzzi, S., Cianni, G. D., Forte, E., Landi, F., Rizzo, M. R., Sesti, G., Succurro, E., & Consoli, A. (2023) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2023.06.021 · Cited by 16
Inpatient Management of T2DM and Hyperglycemia in Older Adults
DeCarlo, K., & Wallia, A. (2019) · Current Diabetes Reports · doi:10.1007/s11892-019-1209-3 · Cited by 15
Risk factors at admission of in-hospital dysglycemia, mortality, and readmissions in patients with type 2 diabetes and pneumonia
Olsen, M. T., Klarskov, C. K., Hansen, K. B., Pedersen‐Bjergaard, U., & Kristensen, P. L. (2024) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2024.108803 · Cited by 14
Spontaneous and iatrogenic hypoglycaemia related to mortality in the ICU
Cichosz, S. L., Redke, F., & Hejlesen, O. K. (2019) · Diabetes & Metabolism · doi:10.1016/j.diabet.2019.02.001 · Cited by 14
Avoiding hypoglycaemia: a new target of care for elderly diabetic patients
Wong, C. (2015) · Hong Kong Medical Journal · doi:10.12809/hkmj144494 · Cited by 14
Single prognostic cut-off value for admission glycemia in acute myocardial infarction has been used although high-risk stems from hyperglycemia as well as from hypoglycemia (a narrative review)
Koracevic, G. P., Mićić, S., Stojanović, M., Tomasevic, M. V., Kostić, T. L., Koraćević, M., & Janković, I. (2020) · Primary care diabetes · doi:10.1016/j.pcd.2020.09.004 · Cited by 14
Aging and comorbidities influence the risk of hospitalization and mortality in diabetic patients experiencing severe hypoglycemia
Nuzzo, A., Brignoli, A., Ponziani, M. C., Zavattaro, M., Prodam, F., Castello, L. M., Avanzi, G. C., Marzullo, P., & Aimaretti, G. (2021) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2021.09.016 · Cited by 13
Evaluation of Outcomes and Complications in Patients Who Experience Hypoglycemia After Cardiac Surgery
Lowden, E., Schmidt, K., Mulla, I., Andrei, A., Cashy, J., Oakes, D. J., Aleppo, G., Grady, K. L., Wallia, A., & Molitch, M. E. (2016) · Endocrine Practice · doi:10.4158/ep161427.or · Cited by 13
Hypoglycemia, Malnutrition and Body Composition
Khanimov, I., Shimonov, M., Wainstein, J., & Leibovitz, E. (2020) · Advances in experimental medicine and biology · doi:10.1007/5584_2020_526 · Cited by 13
Management of hospitalized type 2 diabetes mellitus patients
Marín-Peñalver, J. J., Timon, I. M., & del Cañizo-Gómez, F. J. (2016) · Journal of Translational Internal Medicine · doi:10.1515/jtim-2016-0027 · Cited by 11
Hypoglycaemia Among Diabetes Patients: A Preventive Approach
Mohajan, D., & Mohajan, H. K. (2023) · Journal of Innovations in Medical Research · doi:10.56397/jimr/2023.09.05 · Cited by 12
Management of Type-I Diabetes: A Right Procedure to Normal Life Expectancy
Mohajan, D., & Mohajan, H. K. (2023) · Frontiers in Management Science · doi:10.56397/fms.2023.12.07 · Cited by 12
“However, in severe hypoglycaemia blood glucose levels could be in 2.8 to 3.3mmol/l (Boucai et al., 2011).”
BackgroundInfluential
Challenges and Strategies for Inpatient Diabetes Management in Older Adults
Gosmanov, A. R., Mendez, C. E., & Umpierrez, G. E. (2020) · Diabetes Spectrum · doi:10.2337/ds20-0008 · Cited by 12
Association between dysglycemia and the Charlson Comorbidity Index among hospitalized patients with diabetes
Khan, S. A., Shields, S. A., Abusamaan, M. S., & Mathioudakis, N. N. (2022) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2022.108305 · Cited by 12
Glycaemic status, insulin resistance, and risk of infection-related mortality: a cohort study
Cheong, H. S., Chang, Y., Kim, Y., Joo, E., Kwon, M., Wild, S. H., Byrne, C. D., & Ryu, S. (2023) · European Journal of Endocrinology · doi:10.1093/ejendo/lvad011 · Cited by 10
Top 10 Facts to Know About Inpatient Glycemic Control
Horton, W. B., & Subauste, J. S. (2015) · The American Journal of Medicine · doi:10.1016/j.amjmed.2015.10.007 · Cited by 10
Efficacy and Safety of Empagliflozin Continuation in Patients with Type 2 Diabetes Hospitalised for Acute Decompensated Heart Failure
Perez-Belmonte, L. M., Ricci, M., Sanz‐Cánovas, J., Millán‐Gómez, M., Osuna‐Sánchez, J., Ruiz-Moreno, M. I., Bernal-López, M. R., Lopez-Carmona, M. D., Jiménez-Navarro, M. F., Gómez‐Doblas, J. J., et al. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10163540 · Cited by 10
“Insulin regimens have been linked to a higher risk of hypoglycaemic episodes, which occur in as many as one out of every three treated patients [33].”
Background
Low hemoglobin A1C increases the risk of disability in community-dwelling older non-diabetics adults
Kim, K., Kim, S., Kim, K. W., Jang, H. C., Kim, C.-H., & Chin, H. J. (2015) · The journal of nutrition health & aging · doi:10.1007/s12603-015-0583-z · Cited by 10
“Nonetheless, previous reports showed that hypoglycemic episodes occur even among non-diabetic hospitalized older patients and the increased mortality is not associated drugtreatment but linked with comorbidities (21, 22).”
Inpatient glycemic management in internal medicine: an observational multicenter study in Nanjing, China
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Background
Simplified glycaemic management for patients with type 2 diabetes admitted for acute decompensated heart failure using linagliptin
Perez-Belmonte, L. M., Osuna‐Sánchez, J., Rico-Robles, J. I., Ricci, M., Lara, J. P., & Gómez‐Huelgas, R. (2021) · Medicina Clínica · doi:10.1016/j.medcli.2021.02.009 · Cited by 8
Management of Inpatient Hyperglycemia and Diabetes in Older Adults
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“Treatment with insulin is the most common risk factor for inpatient hypoglycemia (47,51).”
Risk Factors for Glycemic Control in Hospitalized Patients with Type 2 Diabetes Receiving Continuous Subcutaneous Insulin Infusion Therapy
Wang, S.-H., Shao, W., Jiang, Q., Zheng, X., Shen, Q., Lin, X.-Y., Zhang, Q.-Q., Zhang, L., Shi, X., Wang, W.-G., et al. (2022) · Diabetes Therapy · doi:10.1007/s13300-022-01342-9 · Cited by 7
Association Between the Use of Long-Acting Insulin and Hypoglycemia in Nondiabetic Patients in the Surgical Intensive Care Unit
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“Boucai and colleagues reported that increasing age was associated with higher rates of hypoglycemia, and similarly, our study identified age as a significant predictor of hypoglycemia.(27) It has also been shown that higher BMI can reduce the risk of developing hypoglycemia.”

Authors: Boucai, L., Southern, W. N., & Zonszein, J.
Affiliations: Albert Einstein College of Medicine (US)
Corresponding author: Boucai, Laura
ORCID: Boucai, Laura
Zonszein, Joel
Venue: The American Journal of Medicine
Publisher: Elsevier BV
Published: 2011-11
Volume: 124
Issue: 11
Pages: 1028-1035
ISSN: 0002-9343 (ISSN-L)
DOI: 10.1016/j.amjmed.2011.07.011
PMC: PMC3200530
OpenAlex: W2018247534
Cited by: 175
References: 33
Citations by year: 2026: 6 · 2025: 6 · 2024: 9 · 2023: 15 · 2022: 10 · 2021: 9 · 2020: 11 · 2019: 12 · 2018: 9 · 2017: 11 · 2016: 22 · 2015: 16 · 2014: 11 · 2013: 13 · 2012: 14
FWCI: 10.22
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: The American Journal of Medicine (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Center for Research Resources
National Institutes of Health
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hyperglycemia and glycemic control in critically ill and hospitalized patients
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Patient Safety and Medication Errors
Keywords: hypoglycemia, in-hospital mortality, spontaneous hypoglycemia, glucose-lowering medications, comorbidities, tight glycemic control, antidiabetic drugs
MeSH terms: Adult, Aged, Aged, 80 and over, Blood Glucose, Cause of Death, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Female, Humans, Hypoglycemia, Hypoglycemic Agents, Male, Middle Aged, New York City, Retrospective Studies, Risk, Risk Factors, Cohort Studies, Comorbidity, Proportional Hazards Models, Survival Analysis, Hospital Mortality

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Hypoglycemia-associated Mortality Is Not Drug-associated but Linked to Comorbidities

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