Insulin infusion in acute illness

Dandona, Paresh; Mohanty, Priya; Chaudhuri, Ajay; Garg, Rajesh; Aljada, Ahmad

doi:10.1172/jci26045

Cited by 129 publications

(99 citation statements)

References 23 publications

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“…Nontraditional risk factors might represent further links (or intermediate phenotypes) between insulin resistance and CVD. Accordingly, in vitro and in vivo data suggest that insulin reduces platelet aggregation (10) and fibrinogen synthesis (12), possesses antiinflammatory and antioxidant properties (13,14), and favorably influences the endothelial function and the physiology of the vascular wall (11,15,16). If we assume that insulin resistance is not confined to glucose metabolism but encompasses many, if not all, biological effects of the hormone, these effects of insulin would be blunted in insulin-resistant states.…”

Section: Discussionmentioning

confidence: 99%

Insulin Resistance as Estimated by Homeostasis Model Assessment Predicts Incident Symptomatic Cardiovascular Disease in Caucasian Subjects From the General Population

Bonora

Kiechl²,

Willeit³

et al. 2007

Diabetes Care

305

209

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OBJECTIVE -The purpose of this study was to evaluate whether insulin resistance is associated to cardiovascular disease (CVD) and to understand whether this association can be explained by traditional and novel CVD risk factors associated with this metabolic disorder. RESEARCH DESIGN AND METHODS-We examined a sample representative of the population of Bruneck, Italy (n ϭ 919; aged 40 -79 years). Insulin-resistant subjects were those with a score in the top quartile of the homeostasis model assessment (HOMA) for insulin resistance (HOMA-IR). Risk factors correlated with insulin resistance included BMI, A1C, HDL cholesterol, triglycerides, blood pressure, high-sensitivity C-reactive protein (hsCRP), fibrinogen, oxidized LDL, vascular cell adhesion molecule-1 (VCAM-1), and adiponectin. Subjects without CVD at baseline were followed up for 15 years for incident CVD, a composite end point including fatal and nonfatal myocardial infarction and stroke, transient ischemic attack, and any revascularization procedure.RESULTS -During follow-up, 118 subjects experienced a first symptomatic CVD event. Levels of HOMA-IR were higher at baseline among subjects who developed CVD (2.8) compared with those remaining free of CVD (2.5) (P Ͻ 0.05). Levels of HOMA-IR also were significantly correlated (P Ͻ 0.05) with most CVD risk factors we evaluated. In Cox proportional hazard models, insulin-resistant subjects had an age-, sex-, and smoking-adjusted 2.1-fold increased risk (95% CI 1.3-3.1) of incident symptomatic CVD relative to non-insulin-resistant subjects. After sequential adjustment for physical activity and classic risk factors (A1C, LDL cholesterol, and hypertension) as well as BMI, HDL cholesterol, triglycerides, and novel risk factors, including fibrinogen, oxidized LDL, hsCRP, VCAM-1, and adiponectin, the association between HOMA-IR and incident CVD remained significant and virtually unchanged (hazard ratio 2.2 [95% CI 1.4 -3.6], P Ͻ 0.001).CONCLUSIONS -HOMA-estimated insulin resistance is associated with subsequent symptomatic CVD in the general population independently of all classic and several nontraditional risk factors. These data suggest that insulin resistance may be an important target to reduce CVD risk. Diabetes Care 30:318 -324, 2007I nsulin resistance is a pathogenic factor for type 2 diabetes (1,2) and is associated with diverse cardiovascular disease (CVD) risk states, including obesity, essential hypertension, hypertriglyceridemia, and low HDL cholesterol (3). A significant proportion of apparently healthy subjects also are insulin resistant (4,5). In aggregate, insulin resistance and related conditions are very common, affecting as many as 30 -40% of subjects living in affluent countries. Insulin resistance is also a common finding in developing countries. Throughout the world hundreds of millions of people and perhaps even Ͼ1 billion people are estimated to have insulin resistance (6).In recent years the question as to whether insulin resistance is involved in the pathogenesis of CVD has persisted. This ...

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Section: Discussionmentioning

confidence: 99%

Insulin Resistance as Estimated by Homeostasis Model Assessment Predicts Incident Symptomatic Cardiovascular Disease in Caucasian Subjects From the General Population

Bonora

Kiechl²,

Willeit³

et al. 2007

Diabetes Care

305

209

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Section: The Isc Innate Immunity and Aging In Mammalsmentioning

confidence: 99%

“…The anti-inflammatory effects of insulin have been revisited recently in light of the beneficial effects of intensive insulin therapy (IIT) of critically ill patients [28,29]. These patients typically suffer from stress hyperglycemia, so the beneficial effects of IIT have not been clearly attributed to the prevention of hyperglycemia, which can induce oxidative stress, or to the purported anti-inflammatory effects of elevated levels of insulin in vivo [29,30].Taken together, IGF-I and insulin can exert anti-and pro-inflammatory effects on immune cells, but these effects are mediated by low to physiological levels of IGF-I, while an excess of insulin is required to observe similar effects. At high concentrations, insulin can bind to the IGF-I receptor [31], suggesting that the similar effects of insulin and IGF-1 at different doses are due to binding to the IGF-1 receptor.…”

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confidence: 99%

The insulin signaling cascade from nematodes to mammals: Insights into innate immunity of Anopheles mosquitoes to malaria parasite infection

Luckhart

Riehle

2007

Developmental & Comparative Immunology

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As revealed over the past twenty years, the insulin signaling cascade plays a central role in regulating immune and oxidative stress responses that affect the life spans of mammals and two model invertebrates, the nematode Caenorhabitis elegans and the fruit fly Drosophila melanogaster. In mosquitoes, insulin signaling regulates key steps in egg maturation and immunity and likely affects aging, although the latter has yet to be examined in detail. Reproduction, immunity and aging critically influence the capacity of mosquitoes to effectively transmit malaria parasites. Current work has demonstrated that molecules from the invading parasite and the blood meal elicit functional responses in female mosquitoes that are regulated through the insulin signaling pathway or by crosstalk with interacting pathways. Defining the details of these regulatory interactions presents significant challenges for future research, but will increase our understanding of mosquito/malaria parasite transmission and of the conservation of insulin signaling as a key regulatory nexus in animal biology. Keywordsinsulin; Anopheles; Plasmodium; mosquito; malaria; aging; oxidative stress; innate immunity; nitric oxide; transforming growth factor; β In all well-studied metazoans, metabolism, growth, and longevity are coordinately regulated via a nexus that involves signaling cascades activated by insulin and insulin-like growth factors (IGF). Although these pathways differ in downstream physiological effects and some of their signaling proteins, the proteins themselves and their scaffolding interactions are largely conserved among model organisms ( Fig. 1), particularly in the nematode Caenorhabditis elegans, the fruit fly Drosophila melanogaster, and the mouse Mus musculus. This review will examine our current understanding of how the insulin and IGF signaling cascades (ISC) regulate immunity in these diverse model organisms. In addition, we will explore how recent Correspondence to: Shirley Luckhart. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errorsmaybe discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Key targets of daf-16 regulation include genes for mitochondrial manganese superoxide dismutase (MnSOD) and glutathione S-transferase, which are closely linked to aging in C. elegans and other organisms, and genes for numerous C-type lectins, which play critical roles in cell adhesion and pathogen recognition [5]. Downregulation of these gene targets in daf-16 mutants would be predicted to enhance oxidative stress, which has been linked directly to aging in C. elegans [6,7], and decrease pathogen recognition [8]. Conversely, rescue of downregulated MnSOD...

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“…(2, 8-10). Hipergliseminin özellikle, öncesinde diyabeti olmayan hastalarda mortaliteyi artırdığı, immünsüpresif, proinflamatuvar, protrombotik ve hücre membran yapısında bozulmaya neden olduğu, miyokardiyal kontraktiliteyi azalttığı çalışmalarda gösterilmiş-tir (11,(12)(13)(14).…”

Section: İnsülin İnfüzyon Tedavi Protokolüunclassified

Efficacy of an Insulin Infusion Treatment Protocol Administered in a Medical Intensive Care Unit

Coşkun¹,

Gündoğan²,

Guven³

et al. 2012

Yoğun Bakim Derg

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Aim: To evaluate the efficacy of insulin infusion treatment protocol in the Medical Intensive Care Unit. Material and Methods: This study was performed in our Medical Intensive Care Unit (MICU) at an University Hospital. A total of 145 patients who were hospitalized longer than 24 hours in MICU and received insulin infusion treatment were included in the study. Glucose measurements during infusion were analyzed and 4205 measurements were performed. We developed a protocol which aimed to keep the plasma glucose level between 110-150 mg/dL. Results: The mean plasma glucose level of the patients was 178±57 mg/dL. The goal for a glucose level of 110-150 mg/dL was achieved in 26% of the patients. The rate for less than 110 mg/dL was 7%. Levels above 150 mg/dL were seen in 67%. Among levels higher than 150 mg/dL; levels between 150-200 mg/dL was 35%, levels between 200-300 mg/dL was 21%, levels between 300-400 mg/dL was 3% and levels higher than 400 mg/ dL was 1%. The percentage of hypoglycemia was 0.3%. Conclusion: Our protocol provided that plasma glucose levels higher than 150 mg/dL was found to be very frequent. It seems to be safe for hypoglycemia. The protocol should be revised after evaluation of these high glucose levels. ( Abstract ÖzetGiriş Hiperglisemi kritik hastalarda yaygındır ve bu hastalarda morbidite ve mortaliteyi artıran değiştirilebilir bir risk faktörüdür (1). Hiperglisemi sadece hastalığın şiddetini gösteren bir gösterge değil; aynı zamanda ciddi infeksiyonlar, miyokardial infarktüs, polinöropati ve çoklu organ yetmezliği gibi hastanın kliniğini daha da kötüleştiren komplikasyonların riskini de artıran bir problemdir (2-4). On yıldan fazla bir süredir yoğun bakım ünitelerinde hipergliseminin optimal tedavisi ile ilgili çok fazla tartışma yapılmaktadır. Van den Berghe ve arkadaşları (2) 2001 yılında, cerrahi yoğun bakım ünitesinde tek merkezli, prospektif, randomize kontrollü bir çalışmada yoğun kan şekeri kontrolünün (80-110 mg/dL) faydalarını gösterdiler. Bu ilgi uyandıran sonuçtan sonra dün-yadaki yoğun bakım ünitelerinde sıkı kan şekeri kontrolü için değişik insülin infüzyon protokolleri oluşturuldu (2). Yapılan çalışmalarda yoğun bakımda tedavi gören hastalarda kan şekeri kontrolünün faydaları gösterildi (1, 5).Kritik hastalarda optimum kan şekeri hedef değerleri net değildir. Bizim ünitemizde intravenöz insülin infüzyon protokolü 2009 yılında standardize edildi. Bu protokole göre hedef kan şekeri değeri 110-150 mg/dL olarak belirlendi.Çalışmamızın amacı yoğun bakım ünitemizde uygulanan insülin infüzyon tedavi protokolünün kritik hastaların kan şekeri seviyeleri üze-rine etkinliğinin değerlendirilmesidir. Gereç ve YöntemlerTanımlayıcı tipteki bu çalışma bir Üniversite Hastanesi Medikal Yoğun Bakım Ünitesinde (YBÜ) 1 Haziran 2010-1 Haziran 2011 tarihleri arasında yapıldı. Medikal YBÜ'si 18 yataklı sürekli yoğun bakım uzman-

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Insulin infusion in acute illness

Abstract: dase may provide a new therapeutic avenue to block allergic inflammation at its earliest known step and help those of us who live in the pollen belt to better appreciate the arrival of spring.

Cited by 129 publications

References 23 publications

Insulin Resistance as Estimated by Homeostasis Model Assessment Predicts Incident Symptomatic Cardiovascular Disease in Caucasian Subjects From the General Population

Insulin Resistance as Estimated by Homeostasis Model Assessment Predicts Incident Symptomatic Cardiovascular Disease in Caucasian Subjects From the General Population

The insulin signaling cascade from nematodes to mammals: Insights into innate immunity of Anopheles mosquitoes to malaria parasite infection

Efficacy of an Insulin Infusion Treatment Protocol Administered in a Medical Intensive Care Unit

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