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Hypoglycemia-associated Mortality Is Not Drug-associated but Linked to Comorbidities
Open accessAbstract
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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“The risk factors for inpatient hypoglycemia include older age, presence of comorbidities, diabetes, increasing number of antidiabetic agents, tight glycemic control, septic shock, renal insufficiency, mechanical ventilation, and severity of illness (75,76).”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [75]
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“In a retrospective study of 31,970 patients admitted to the general wards of an academic medical center in 2007, a total of 3,349 patients (10.5%) had at least one episode of hypoglycemia (≤70 mg/dL) (75).”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [75]
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“Oral DPP-4 inhibitors have been tested in RCTs in medical and surgical noncritically ill persons with mild hyperglycemia (admission glucose <180 mg/dL).1351,1354–1357”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [1357]
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“DPP-4 inhibitors combined with low-dose basal insulin have been similarly effective to basal-bolus insulin and associated with less hypoglycemia and less treatment burden.1351,1354–1357,1359”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [1357]
Experimental — accuracy not yet measuredIn the citing paper
“In a retrospective study of 31,970 patients admitted to the general wards of an academic medical center in 2007, a total of 3,349 patients (10.5%) had at least one episode of hypoglycemia ( # 70 mg/dL) (75).”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [75]
In the citing paper
“The risk factors for inpatient hypoglycemia include older age, presence of comorbidities, diabetes, increasing number of antidiabetic agents, tight glycemic control, septic shock, renal insuf fi ciency, mechanical ventilation, and severity of illness (75,76).”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [75]
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BackgroundInfluentialSex difference in the association between malnutrition and hypoglycemia in hospitalized patients
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“Although it is unknown whether this same risk extends to patients with recurrent hypoglycaemia within one monitored patient-day, we submit that this measure is an important evaluation of quality of care as the first hypoglycaemic event should trigger treatment changes that serve to minimize the risk of subsequent hypo…”
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FATORES DE RISCO ASSOCIADOS À HIPOGLICEMIA E ANÁLISE DE EVENTOS ADVERSOS EM UMA TERAPIA INTENSIVA
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“Hyperglycemia and hypoglycemia each increase risks for complications and patient deaths [3,16].”
Hypoglycemia is a strong independent predictor of mortality in acute calculous cholecystitis
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German, N., Popov, A., & Ramanavičienė, A. (2026) · Polymers · doi:10.3390/polym18111273 · Cited by 1
“Hypoglycemia (glucose concentration in the plasma is lower than 70 mg/dL (3.88 mM)) in diabetic persons is linked to morbidity and mortality, and presents a significant challenge to maintaining proper glycemic control [12].”
InfluentialHabashy, N. S., Low, G. K. K., & Hibbert, E. J. (2026) · Diabetology · doi:10.3390/diabetology7100204
Metadata
- Authors
- Boucai, L., Southern, W. N., & Zonszein, J.
- Affiliations
- Albert Einstein College of Medicine (US)
- Corresponding author
- Boucai, Laura
- Venue
- The American Journal of Medicine
- Publisher
- Elsevier BV
- Published
- 2011-11
- Volume
- 124
- Issue
- 11
- Pages
- 1028-1035
- ISSN
- 0002-9343 (ISSN-L)
- 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
- 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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