title: Insulin resistance in critical illness.
abstract: OBJECTIVE
  The purpose of this review is to describe current concepts on inflammation, immunity and insulin resistance. Metabolic and immune systems are closely involved in inflammation and significantly contribute to the pathology seen in the pediatric intensive care unit. The ability of insulin to decrease hepatic glucose production, suppress adipose tissue lipolytic rate, stimulate skeletal muscle glucose uptake, suppress protein breakdown and increase protein synthesis is critical to maintain metabolic function. Hence, a better understanding of these regulatory mechanisms and the alterations leading to dysfunction will set the basis for a better metabolic and immune support of critically ill patients.
  
  
  RESULTS
  Inflammation can be elicited by infection (sepsis) through pathogen associated molecular patterns (PAMPs) or through danger associated molecular patterns (DAMPs) as a response to an insult (systemic inflammatory response syndrome; SIRS) in the absence of infection. Mitochondrial DAMPs and PAMPs share the same pattern recognition receptors. These receptors act also as nutrient sensors, and in the presence of fatty acids will induce an inflammatory cascade that affects insulin signaling with development of insulin resistance. Lipotoxicity is emerging as a significant contributor to the development of insulin resistance.
  
  
  CONCLUSIONS
  Insulin resistance is an adaptive mechanism that prioritizes utilization of energy for immune response in the presence of infection or injury. A better understanding of the complex interactions between metabolism, inflammation and immunity in critically ill children will lead to appropriate metabolic and immune support of these patients.
authors.affiliation: Division of Critical Care, Department of Pediatrics, Children's Medical Center, University of Texas Southwestern, Dallas, USA.
authors.forename: Archana
authors.initials: A
authors.lastname: Dhar
authors.forename: Leticia
authors.initials: L
authors.lastname: Castillo
mesh_terms: D002648:Child; D016638:Critical Illness; D006801:Humans; D006943:Hyperglycemia / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D015228:Hypertriglyceridemia / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D007249:Inflammation / Q000276:immunology / Q000378:metabolism*; D007333:Insulin Resistance / Q000276:immunology / Q000502:physiology*