Trial reportCritical care (London, England)2011
sRAGE in diabetic and non-diabetic critically ill patients: effects of intensive insulin therapy.
Trial report in Critical care (London, England), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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.
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Who cites it
12 citing papers in PubMed, 19 citations in OpenAlex.
- Association between enteral carboxymethyllysine intake and daily glycemic variability in critically ill adults: A retrospective cohort study.JPEN. Journal of parenteral and enteral nutrition · 2025Article
- The Association Between Dysglycemia and Endotheliopathy in ICU Patients With and Without Diabetes: A Cohort Study.Critical care explorations · 2025Observational
- Hyperactivated RAGE in Comorbidities as a Risk Factor for Severe COVID-19-The Role of RAGE-RAS Crosstalk.Biomolecules · 2021Review
- COVID-19 and Diabetes: The Importance of Controlling RAGE.Frontiers in endocrinology · 2020Article
- Hyperglycemia-Driven Neuroinflammation Compromises BBB Leading to Memory Loss in Both Diabetes Mellitus (DM) Type 1 and Type 2 Mouse Models.Molecular neurobiology · 2019Article
- Diabetes-Specific Formulae Versus Standard Formulae as Enteral Nutrition to Treat Hyperglycemia in Critically Ill Patients: Protocol for a Randomized Controlled Feasibility Trial.JMIR research protocols · 2018Article
- Soluble RAGEs - Prospects for treating & tracking metabolic and inflammatory disease.Vascular pharmacology · 2015Review
- The altered renal and hepatic expression of solute carrier transporters (SLCs) in type 1 diabetic mice.PloS one · 2015Article
- Elevation of high-mobility group box 1 after clinical autologous islet transplantation and its inverse correlation with outcomes.Cell transplantation · 2014Article
- Soluble receptor for advanced glycation end products in critically ill patients and its associations with other clinical markers and 28-day mortality.Clinical interventions in aging · 2014Article
- Potential of the angiotensin receptor blockers (ARBs) telmisartan, irbesartan, and candesartan for inhibiting the HMGB1/RAGE axis in prevention and acute treatment of stroke.International journal of molecular sciences · 2013Review
- Receptor for advanced glycation end products (RAGE) and implications for the pathophysiology of heart failure.Current heart failure reports · 2012Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionHyperglycemia represents an independent prognostic factor in critically ill non-diabetic patients but not in those with diabetes. In this context, there is an ongoing debate on the benefit of an intensive insulin therapy, particularly in diabetic patients. We tested the hypothesis that expression of the receptor for advanced glycation end-products (RAGE), an important signal transduction receptor that elicits long-lasting nuclear factor kappa B (NF-κB) activation, may underlie this difference. RAGE expression is regulated by multiple ligands, including high mobility group box-1 (HMGB-1), and is reflected by its released soluble form (sRAGE).
methodsA predesigned analysis was conducted of prospectively collected samples from 76 hyperglycemic critically ill patients (33 type-2 diabetes, 43 non-diabetes) aged ≥ 18 years with blood glucose of > 6.1 mmol/L enrolled in a randomized controlled trial comparing intensive insulin therapy with conventional insulin therapy. sRAGE and its ligand HMGB-1 together with IL-6, and soluble thrombomodulin (as markers of inflammation and endothelial cell injury, respectively) were evaluated in ICU, at Days 1, 3, 5 and 7. Plasma samples from 18 healthy subjects were used as controls.
resultsBoth diabetic and non-diabetic hyperglycemic patients showed increased plasma sRAGE, HMGB-1 and soluble thrombomodulin levels at the time of admission to ICU. Plasma IL-6 concentration was only increased in non-diabetic patients. Plasma levels of sRAGE were higher in diabetic compared with non-diabetic patients. Intensive insulin therapy resulted in a significant decrease of sRAGE and thrombomodulin at Day 7, in diabetic but not in non-diabetic patients. Circulating sRAGE levels correlated positively with IL-6 and soluble thrombomodulin levels and inversely with HMGB-1. Multivariate regression analysis demonstrated that sRAGE remains independently correlated with HMGB-1 only in diabetic patients. Neither sRAGE nor any inflammatory markers are associated with mortality.
conclusionsThese findings support the hypothesis that sRAGE release, time-course and response to intensive insulin therapy differ between hyperglycemic diabetic and non-diabetic critically ill patients. Whether this difference underlies the dissimilarity in clinical outcome of hyperglycemia in these two conditions warrants further studies.
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