Trial reportThe Journal of clinical investigation2005
Intensive insulin therapy protects the endothelium of critically ill patients.
Trial report in The Journal of clinical investigation, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 125 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
125 citing papers in PubMed, 3 syntheses or guidelines pooled it, 465 citations in OpenAlex.
- Impact of tight blood glucose control on atrial fibrillation in critically ill patients receiving early parenteral nutrition: an individual patient data meta-analysis of two large randomized controlled trials.Journal of cardiothoracic surgery · 2026Pooled it
- Interventions for preventing critical illness polyneuropathy and critical illness myopathy.The Cochrane database of systematic reviews · 2014Pooled it
- Clinical review: Critical illness polyneuropathy and myopathy.Critical care (London, England) · 2008Pooled it
- Effect of Permissive Underfeeding with Intensive Insulin Therapy on MCP-1, sICAM-1, and TF in Critically Ill Patients.Nutrients · 2019Trial
- Intraoperative tight glucose control using hyperinsulinemic normoglycemia increases delirium after cardiac surgery.Anesthesiology · 2015Trial
- Critical illness induces nutrient-independent adipogenesis and accumulation of alternatively activated tissue macrophages.Critical care (London, England) · 2013Trial
- Pilot study of the SPRINT glycemic control protocol in a Hungarian medical intensive care unit.Journal of diabetes science and technology · 2012Trial
- sRAGE in diabetic and non-diabetic critically ill patients: effects of intensive insulin therapy.Critical care (London, England) · 2011Trial
- Insulin suppresses endotoxin-induced oxidative, nitrosative, and inflammatory stress in humans.Diabetes care · 2010Trial
- Tight blood glucose control is renoprotective in critically ill patients.Journal of the American Society of Nephrology : JASN · 2008Trial
- Hypoglycaemia: the limiting factor in the glycaemic management of the critically ill?Diabetologia · 2006Trial
- Bispecific Antibodies in B-Cell Lymphomas: Mechanisms, Efficacy, Toxicity, and Management.Medicina (Kaunas, Lithuania) · 2026Review
- The association between triglyceride glucose-body mass index and mortality in intensive care unit patients: a propensity score matching analysis.European journal of medical research · 2025Article
- Optimising cardiac surgery outcomes in people with diabetes: the OCTOPuS pilot feasibility study.Health technology assessment (Winchester, England) · 2025Article
- Integrated Metabolomics and Lipidomics Analysis Reveals the Mechanism Behind the Action of Chiglitazar on the Protection Against Sepsis-Induced Acute Lung Injury.Metabolites · 2025Article
- The Association Between Dysglycemia and Endotheliopathy in ICU Patients With and Without Diabetes: A Cohort Study.Critical care explorations · 2025Observational
- Effect of short-term intensive insulin pump therapy on serum endotrophin levels in patients with newly diagnosed type 2 diabetes.Frontiers in endocrinology · 2025Article
- Risk factors and clinical outcome of postoperative hyperglycemia after cardiac surgery with cardiopulmonary bypass.Frontiers in cardiovascular medicine · 2025Article
- The impact of pre-transplantation diabetes and obesity on acute graft-versus-host disease, relapse and death after allogeneic hematopoietic cell transplantation: a study from the EBMT Transplant Complications Working Party.Bone marrow transplantation · 2024Article
- Inflammatory and endothelial host responses in community-acquired pneumonia: exploring the relationships with HbA1c, admission plasma glucose, and glycaemic gap-a cross-sectional study.Frontiers in immunology · 2024Article
65 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The vascular endothelium controls vasomotor tone and microvascular flow and regulates trafficking of nutrients and biologically active molecules. When endothelial activation is excessive, compromised microcirculation and subsequent cellular hypoxia contribute to the risk of organ failure. We hypothesized that strict blood glucose control with insulin during critical illness protects the endothelium, mediating prevention of organ failure and death. In this preplanned subanalysis of a large, randomized controlled study, intensive insulin therapy lowered circulating levels of ICAM-1 and tended to reduce E-selectin levels in patients with prolonged critical illness, which reflects reduced endothelial activation. This effect was not brought about by altered levels of endothelial stimuli, such as cytokines or VEGF, or by upregulation of eNOS. In contrast, prevention of hyperglycemia by intensive insulin therapy suppressed iNOS gene expression in postmortem liver and skeletal muscle, possibly in part via reduced NF-kappaB activation, and lowered the elevated circulating NO levels in both survivors and nonsurvivors. These effects on the endothelium statistically explained a significant part of the improved patient outcome with intensive insulin therapy. In conclusion, maintaining normoglycemia with intensive insulin therapy during critical illness protects the endothelium, likely in part via inhibition of excessive iNOS-induced NO release, and thereby contributes to prevention of organ failure and death.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.