Intensive insulin therapy in the medical ICU
Open accessAbstract
BACKGROUND: Intensive insulin therapy reduces morbidity and mortality in patients in surgical intensive care units (ICUs), but its role in patients in medical ICUs is unknown. METHODS: In a prospective, randomized, controlled study of adult patients admitted to our medical ICU, we studied patients who were considered to need intensive care for at least three days. On admission, patients were randomly assigned to strict normalization of blood glucose levels (80 to 110 mg per deciliter [4.4 to 6.1 mmol per liter]) with the use of insulin infusion or to conventional therapy (insulin administered when the blood glucose level exceeded 215 mg per deciliter [12 mmol per liter], with the infusion tapered when the level fell below 180 mg per deciliter [10 mmol per liter]). There was a history of diabetes in 16.9 percent of the patients. RESULTS: In the intention-to-treat analysis of 1200 patients, intensive insulin therapy reduced blood glucose levels but did not significantly reduce in-hospital mortality (40.0 percent in the conventional-treatment group vs. 37.3 percent in the intensive-treatment group, P=0.33). However, morbidity was significantly reduced by the prevention of newly acquired kidney injury, accelerated weaning from mechanical ventilation, and accelerated discharge from the ICU and the hospital. Although length of stay in the ICU could not be predicted on admission, among 433 patients who stayed in the ICU for less than three days, mortality was greater among those receiving intensive insulin therapy. In contrast, among 767 patients who stayed in the ICU for three or more days, in-hospital mortality in the 386 who received intensive insulin therapy was reduced from 52.5 to 43.0 percent (P=0.009) and morbidity was also reduced. CONCLUSIONS: Intensive insulin therapy significantly reduced morbidity but not mortality among all patients in the medical ICU. Although the risk of subsequent death and disease was reduced in patients treated for three or more days, these patients could not be identified before therapy. Further studies are needed to confirm these preliminary data. (ClinicalTrials.gov number, NCT00115479.)
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Aggressive lowering of glycemia in the ICU may be associated with increased mortality.
“However, subsequent studies showed that such aggressive lowering of glycemia in the ICU is not uniformly beneficial, markedly increases the risk of severe hypoglycemia, and may be associated with increased mortality (70–74).”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [73]
Experimental — accuracy not yet measuredAggressive lowering of glycemia in the ICU is not uniformly beneficial.
“However, subsequent studies showed that such aggressive lowering of glycemia in the ICU is not uniformly beneficial, markedly increases the risk of severe hypoglycemia, and may be associated with increased mortality (70–74).”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [73]
Experimental — accuracy not yet measuredAggressive lowering of glycemia in the ICU markedly increases the risk of severe hypoglycemia.
“However, subsequent studies showed that such aggressive lowering of glycemia in the ICU is not uniformly beneficial, markedly increases the risk of severe hypoglycemia, and may be associated with increased mortality (70–74).”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [73]
In hospitalized patients with and without diabetes, hyperglycemia predicts poor clinical outcome and mortality.
“Observational studies in hospitalized patients with and without diabetes indicate that hyperglycemia is a predictor of poor clinical outcome and mortality.1–4”
From A comparison study of continuous insulin infusion protocols in the medical intensive care unit: Computer-guided vs. Standard column-based algorithms (2010) · cites this paper as [3]
Early randomized trials of intensified insulin therapy in surgical and medical acute critical illness reported reduced risk of multiorgan failure, systemic infections, and short- and long-term mortality.
“Early randomized controlled trials of intensified insulin therapy in patients with surgical and medical acute critical illness reported a reduction on the risk of multiorgan failure and systemic infections,3–5 as well as short- and long-term mortality.1,4”
From A comparison study of continuous insulin infusion protocols in the medical intensive care unit: Computer-guided vs. Standard column-based algorithms (2010) · cites this paper as [3]
The overall rate of severe hypoglycemic events in international trials ranged from 5% to 28.6%.
“The overall rate of severe hypoglycemic events in international trials ranged between 5% to 28.6%.3,4,7,8,18,19”
From A comparison study of continuous insulin infusion protocols in the medical intensive care unit: Computer-guided vs. Standard column-based algorithms (2010) · cites this paper as [3]
The rate of severe hypoglycemia (<40 mg/dL) in this trial was lower than rates reported in recent international trials of intensive glycemic control.
“The rate of severe hypoglycemic events (<40 mg/dL) observed in both arms of our trial was significantly lower than those reported in recent international trials of intensive glycemic control.3,4,8”
From A comparison study of continuous insulin infusion protocols in the medical intensive care unit: Computer-guided vs. Standard column-based algorithms (2010) · cites this paper as [3]
Aggressive lowering of glycemia in the ICU may be associated with increased mortality.
“However, subsequent studies showed that such aggressive lowering of glycemia in the ICU is not uniformly bene fi cial, markedly increases the risk of severe hypoglycemia, and may be associated with increased mortality (70 -74).”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [73]
Aggressive lowering of glycemia in the ICU is not uniformly beneficial.
“However, subsequent studies showed that such aggressive lowering of glycemia in the ICU is not uniformly bene fi cial, markedly increases the risk of severe hypoglycemia, and may be associated with increased mortality (70 -74).”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [73]
Aggressive lowering of glycemia in the ICU markedly increases the risk of severe hypoglycemia.
“However, subsequent studies showed that such aggressive lowering of glycemia in the ICU is not uniformly bene fi cial, markedly increases the risk of severe hypoglycemia, and may be associated with increased mortality (70 -74).”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [73]
A subsequent study of a similar intervention in patients in a medical ICU showed that the group receiving intensive insulin therapy had reduced morbidity but no difference in mortality overall.
“A subsequent study of a similar intervention in patients in a medical ICU (330) showed that the group receiving intensive insulin therapy had reduced morbidity but no difference in mortality overall.”
From Standards of Medical Care in Diabetes—2009 (2009) · cites this paper as [330]
There is relatively strong evidence from randomized controlled trials for a glycemic target of blood glucose <110 mg/dl in surgical patients in critical care units.
“There is relatively strong evidence from randomized controlled trials for a glycemic target of blood glucose <110 mg/dl (6.1 mmol/l) in surgical patients in critical care units (328–330).”
From Standards of Medical Care in Diabetes—2009 (2009) · cites this paper as [330]
In several studies of critically ill medical patients, the incidence of severe hypoglycemia (blood glucose <40 mg/dl) was approximately threefold greater in intensively treated patients.
“However, in several studies of critically ill medical patients (330,331,333), the incidence of severe hypoglycemia (blood glucose <40 mg/dl) was approximately threefold greater in intensively treated patients.”
From Standards of Medical Care in Diabetes—2009 (2009) · cites this paper as [330]
In that medical ICU study, death rates were significantly lower in those patients who were treated for longer than 3 days; but these patients could not be identified before therapy.
“Death rates were significantly lower in those patients who were treated for longer than 3 days; but these patients could not be identified before therapy.”
From Standards of Medical Care in Diabetes—2009 (2009) · cites this paper as [330]
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- Authors
- Van den Berghe, G., Wilmer, A., Hermans, G., Meersseman, W., Wouters, P. J., Milants, I., Van Wijngaerden, E., Bobbaers, H., & Bouillon, R.
- Affiliations
- KU Leuven (BE)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2006-02-02
- Volume
- 354
- Issue
- 5
- Pages
- 449-461
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2115285670
- Cited by
- 3,639
- References
- 28
- Citations by year
- 2026: 40 · 2025: 46 · 2024: 53 · 2023: 51 · 2022: 58 · 2021: 94 · 2020: 89 · 2019: 89 · 2018: 92 · 2017: 121 · 2016: 137 · 2015: 165 · 2014: 203 · 2013: 185 · 2012: 232
- FWCI
- 302.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Novo Nordisk
- Servier
- 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 › Critical Care and Intensive Care Medicine › Intensive Care Unit Cognitive Disorders
- Keywords
- intensive insulin therapy, glycemic control, blood glucose normalization, medical intensive care unit, in-hospital mortality, morbidity, acute kidney injury, weaning from mechanical ventilation, ICU length of stay, history of diabetes, critically ill patients
- MeSH terms
- Aged, Blood Glucose, Critical Care, Female, Humans, Hypoglycemic Agents, Insulin, Intensive Care Units, Kidney Diseases, Length of Stay, Male, Middle Aged, Prognosis, Ventilator Weaning, Proportional Hazards Models, Survival Analysis, Critical Illness, Treatment Outcome, Hospital Mortality, APACHE
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