The roles of insulin and hyperglycemia in sepsis pathogenesis (original) (raw)
Related papers
Insulin in sepsis and septic shock
The Journal of the Association of Physicians of India, 2003
NF-kappaB activation, and elevated concentrations of macrophage migration inhibitory factor (MIF), tumor necrosis factor-alpha (TNF-alpha), interleukin-1(IL-1), IL-6, free radicals, inducible nitric oxide (iNO), and stress hyperglycemia occurs in sepsis and this leads to systemic inflammatory response and myocardial depression seen in sepsis and septic shock. Conversely, insulin suppresses production of MIF, TNF-alpha, IL-1, IL-6, and free radicals, enhances endothelial NO generation, and enhances the production of anti-inflammatory cytokines IL-4, and IL-10, corrects stress hyperglycemia and improves myocardial function. This supports my earlier proposal that insulin (with or without glucose and potassium) therapy to maintain euglycemia suppresses the inflammatory response, improves myocardial function, and thus, is of benefit in acute myocardial infarction, sepsis andseptic shock.
2013
Severe metabolic derangement is characteristic of systemic inflammatory response in septic conditions. Changes in blood glucose levels are often deleterious further impairing organ functioning. Thus they are a subject of strict and sometimes even too aggressive control. Its disadvantages demand and stimulate research of new strategies. In the present paper we systematically review the current therapeutic options and recent research advances in the field of hyperglycemia in sepsis. They include the pathogenesis of sepsis and the role of insulin in this pathology. A special attention is paid to the glycemic control in sepsis. The correct strategy of glycemic control is combined approach with computerized infusion, continuous blood glucose monitoring and proper feeding support. Scripta Scientifica Medica 2013; 45(1): 7-11.
Blood insulin responses to blood glucose levels in high output sepsis and septic shock
The American Journal of Surgery, 1978
and reduced pancreatic insulin secretion are well known features of hypovolemic shock [I, 2]. More recently low blood insulin levels also have been recognized as characteristic of stress in septic shock [3-51. However, in the clinical course of the seriously septic patient, when the circulatory stress has been resolved and equilibrium has been established, it appears that the situation is different. Clinical and experimental observations by our group and others have indicated that blood insulin levels relative to blood glucose levels approach normal values in severely infected patients who are doing well with the high cardiac outputs typical of the recovery pattern [3-61. Because of the importance of blood insulin levels in the energy metabolism of glucose and other substrates, both in health [ 71 and disease, data are presented from a series of observations in thirty-eight patients with major infections whose circulatory status was determined by cardiac outputs, measured at the same times as blood samples were drawn. Since hepatic glucogenesis and the body glucose pool are known to be increased in sepsis [8-101, measurements of the principal glucogenic precursors in the blood, lactate and alanine ]11], were also made simultaneously. In addition to differentiating significantly the insulin responses of the patients with high and low cardiac outputs, the data from both groups are compared with blood glucose and insulin values obtained from thirty-five normal people during glucose tolerance tests. The results indicate that, in
Annals of The Royal College of Surgeons of England, 2004
Loss of the anabolic effect of insulin (insulin resistance) is a key component of the adverse metabolic consequences of sepsis and may contribute to the apparent lack of efficacy of feeding regimens in critically ill patients. The mechanisms which underlie the development of insulin resistance in stress remain unclear. In this series of studies, the locus of insulin resistance in the septic patient was shown to lie within the metabolic pathways of glucose storage (glycogen synthesis) within skeletal muscle, was noted to be unrelated to the actions of hormone mediators such as leptin and was shown not to be associated with altered nutrient-induced thermogenesis during total parenteral nutrition (TPN). Clinically applicable maximal rates of glucose-based TPN for septic patients were calculated. A technique was also developed in which insulin resistance could be induced and studied in healthy volunteers. These studies demonstrated that insulin resistance develops within 7 h of an inflammatory stimulus and, as in clinical sepsis, is characterised by selective impairment of glucose storage. Finally, a series of related studies indicated that the magnitude and nature of the inflammatory response in vivo could be enhanced by exogenous insulin infusion, indicating links between the hormone systems involved in intermediary metabolism and the inflammatory response. These findings have significant implications for the optimal design of feeding regimens for critically ill patients.
Hyperglycemia in sepsis is a risk factor for development of type II diabetes
Journal of Critical Care, 2010
Hyperglycemia is frequent in sepsis, even in patients without diabetes or impaired glucose metabolism. It is a consequence of inflammatory response and stress, so its occurrence is related to severity of illness. However, not all severely ill develop hyperglycemia and some do even in mild disease. We hypothesized the existence of latent disturbance of glucose metabolism that contributes to development of hyperglycemia and that those patients might have increased risk for diabetes.Patients admitted with sepsis and no history of impaired glucose metabolism were included and divided in the hyperglycemia group (glucose ≥7.8 mmol/L) and normoglycemia group. Severity of sepsis was assessed. Surviving patients without diabetes at discharge were followed-up for 5 years to investigate risk for development of diabetes.Hyperglycemia was related to severity of sepsis. Follow-up was finished for 55 patients with hyperglycemia, of which 8 (15.7%) developed diabetes, and 118 patients with normoglycemia, of which 5 (4.2%) developed diabetes (P = .002). Relative risk for developing type 2 diabetes was 4.29 (95% CI, 1.35-13.64).Patients with hyperglycemia in sepsis who are not diagnosed with diabetes before or during the hospitalization should be considered a population at increased risk for developing diabetes.
Insulin-mediated glucose uptake by individual tissues during sepsis
Metabolism, 1990
Gram-negative hypermetabolic sepsis has been previously reported to produce whole body insulin resistance. The present study was performed to determine in vivo which tissues are responsible for the sepsis-induced decrease in insulin-mediated glucose uptake (IMGU). and whether that decrease was related to a change in regional blood flow. Vascular catheters were placed in rats and sepsis was induced by subcutaneous injections of Escherichia coli. Insulin action was assessed 20 hours after the first injection of bacteria by the combined use of the euglycemic hyperinsulinemic clamp and the tracer 2-deoxyglucose IdGlc) technique. Insulin was infused at various rates in separate groups of septic and nonseptic rats for 3 hours to produce steady-state insulin levels between 70 and 20,000 pU/mL. Rats were injected with [U-'4C]-dGlc 140 minutes after the start of the euglycemic hyperinsulinemic clamp for determination of the glucose metabolic rate (Rg) in selected tissues. The maximal response to insulin was decreased 30% to 40% in the gastrocnemius, and in the red and white quadriceps. The former two muscles also showed a decrease in insulin sensitivity. However, the insulin resistance seen in hindlimb muscles was not evident in all muscles of the body, since tMGU by abdominal muscle, diaphragm, and heart wes not impaired by sepsis. The basal Rg by skin, spleen, ileum, and lung was increased by sepsis, and was higher than the insulin-stimulated increases in Rg by these tissues in nonseptic animals. Cardiac output was similar in septic and nonseptic rats and did not change during the infusion of insulin. Under basal conditions, sepsis appeared to redistribute blood flow away from the red quadriceps and skin, and increased flow to the liver (arterial), lung, and small intestine. When plasma insulin levels were elevated, hepatic arterial blood flow was increased, and flow to the red quadriceps and skin was decreased in nonseptic animals. Hyperinsulinemia did not produce any consistent change in regional blood flow in septic animals. The results of this study indicate that a decrease rate of IMGU in muscle is primarily responsible for the whole body insulin resistance seen during hypermetabolic sepsis, and that the impairment of insulin action in skeletal muscle is not
HillenbrandA WeissM 2012 Intern J Inflamm Rev Adipokine Sepsis Insulin 972368
Background. Assessment of white adipose tissue has changed in recent years, with WAT now being considered as an active endocrine organ, secreting a large number of bioactive mediators, so-called adipokines. Besides other functions, these adipokines are involved in inflammatory response thereby exhibiting predominantly proinflammatory or anti-inflammatory properties and contribute to insulin resistance. Methods. Comprehensive review of the literature of the role of adipokines relevant to critical care medicine using PubMed search. Results. Adiponectin-the prototype of an anti-inflammatory and insulin-sensitizing adipokine-is diminished in sepsis, while resistin-a protein with proinflammatory properties-is elevated. Plasminogen activator inhibitor-1, interleukin (IL)-1, IL-6, IL-8, and IL-10, and tumor-necrosis-factor-alpha mediate insulin resistance and are elevated in sepsis, while retinolbinding protein-4 concentrations are significantly reduced in sepsis. Chemerin displays potent anti-inflammatory and insulinresistance properties, while monocyte chemotactic protein-1-increased in sepsis-contributes to macrophage infiltration in adipose tissue and insulin resistance. Conclusions. The expression of adipokines in humans is altered as well in obese as in septic patients with elevated levels of proinflammatory adipokines. Changes in adipokine levels in acute sepsis could contribute to insulin resistance. Consequently, in critically ill patients, these alterations underline a possible contribution of adipokines in the development of hyperglycemia.
The Journal of Clinical Endocrinology & Metabolism, 2006
Context: Hyperglycemia and insulin resistance are common findings in critically ill adult patients and are associated with increased morbidity and mortality. Objectives: The objective of this study was to investigate the hyperglycemic response to critical illness in children. Design: The study was designed as an observational cohort study. Setting: The study was set in a university-affiliated pediatric intensive care unit. Patients: Six children with meningococcal sepsis (MS) without shock and 10 children with meningococcal septic shock (MSS) were patients. Main Outcome Measures: Differences in blood glucose levels (measured during 72 h after admission) and differences in plasma levels of glucoregulatory hormones (insulin, GH, IGF-I, cortisol, glucagons, leptin), soluble cytokine receptors (sTNF-R55, R75, sIL-1R2), and IL-6 (measured on d 3) between MS and MSS patients were assessed. Results: Blood glucose levels on d 2 and 3 were higher in MSS patients than in MS patients [7.5 (3.9-13.0) vs. 5.1 (4.0-6.0) and 6.5 (4.0-9.9) vs. 5.5 (4.8-6.8) mmol/liter, both P Ͻ 0.05]. Maximum blood glucose values recorded in individual patients were higher in MSS patients [9.3 (6.5-13) vs. 7.2 (6.2-9.9), P Ͻ 0.05] and correlated with severity of illness (r ϭ 0.833, P Ͻ 0.001). Insulin levels in MSS patients were significantly lower (7.2 vs. 19.0 mU/liter, P Ͻ 0.001), compatible with insufficient insulin response to hyperglycemia, whereas MS patients showed insulin resistance. Insulin levels correlated inversely with levels of sTNF-R55 and R75 (r ϭ Ϫ0.814 and Ϫ0.878, both P Ͻ 0.001), suggesting suppression of the proinflammatory response on insulin secretion. Conclusion: Hyperglycemia associated with hypoinsulinemia rather than insulin resistance may be the normal pathophysiological response in acute MSS in children. Our study emphasizes that application of intensive insulin therapy in critically ill children demands further investigation.
Critical Care, 2012
Introduction: The aim of the present study was to investigate the relationship between the blood IL-6 level, the blood glucose level, and glucose control in septic patients. Methods: This retrospective observational study in a general ICU of a university hospital included a total of 153 patients with sepsis, severe sepsis, or septic shock who were admitted to the ICU between 2005 and 2010, stayed in the ICU for 7 days or longer, and did not receive steroid therapy prior to or after ICU admission. The severity of stress hyperglycemia, status of glucose control, and correlation between those two factors in these patients were investigated using the blood IL-6 level as an index of hypercytokinemia. Results: A significant positive correlation between blood IL-6 level and blood glucose level on ICU admission was observed in the overall study population (n = 153; r = 0.24, P = 0.01), and was stronger in the nondiabetic subgroup (n = 112; r = 0.42, P < 0.01). The rate of successful glucose control (blood glucose level < 150 mg/dl maintained for 6 days or longer) decreased with increase in blood IL-6 level on ICU admission (P < 0.01). The blood IL-6 level after ICU admission remained significantly higher and the 60-day survival rate was significantly lower in the failed glucose control group than in the successful glucose control group (P < 0.01 and P < 0.01, respectively). Conclusions: High blood IL-6 level was correlated with hyperglycemia and with difficulties in glucose control in septic patients. These results suggest the possibility that hypercytokinemia might be involved in the development of hyperglycemia in sepsis, and thereby might affect the success of glucose control.