Review ArticleHyperglycemia, Insulin, and Insulin Resistance in Sepsis
Introduction
Insulin is an essential hormone with multiple biochemical effects. Clinical studies typically focus on glucose metabolism and consider situations in which there is inadequate insulin production or insulin resistance. Patients with sepsis and other acute medical disorders frequently have hyperglycemia; this develops acutely and does not require the premorbid condition of diabetes. Potential explanations include an imbalance between anabolic hormones (insulin) and catabolic hormones and the acute development of insulin resistance. These complex events make it difficult to know whether high glucose levels just reflect the severity of the acute stress or whether they contribute directly to poor outcomes. Studies on insulin levels and insulin resistance in patients with acute systemic illness have the potential to clarify the role of various factors relevant to hyperglycemia and the potential utility of insulin administration independent of glucose levels.
Section snippets
Insulin
Insulin is an anabolic hormone with three main functions: modulation of cellular metabolism, cell growth and differentiation, and receptor internalization. Its release is stimulated by glucose entering the beta cells via GLUT-2 facilitated diffusion, and it is mainly cleared by insulinase in the liver and kidneys.1 In cellular metabolism, insulin has a role in carbohydrate, protein, and lipid homeostasis. It increases glucose uptake in adipose and muscle tissues by promoting the translocation
Insulin receptors
Increases in blood glucose levels stimulate the pancreas to secrete insulin; its signaling is initiated through binding to insulin receptors located mostly on the surface of liver, muscle, adipose cells, pancreatic beta cells, and pancreatic alpha cells. The insulin receptor is composed of an extracellular domain made of 2 alpha subunits and an intracellular domain made of 2 beta subunits. The binding of insulin to the alpha domain results in conformational changes in membrane-bound
Insulin resistance
Systemic insulin resistance refers to impaired biologic responses to insulin; it manifests with decreased glucose transport and metabolism in skeletal muscle and adipose tissue, failure of insulin to suppress gluconeogenesis in the liver, and failure of insulin to suppress lipolysis in the adipose tissue. Processes that interfere with the phosphorylation of the insulin receptor and insulin receptor substrates result in insulin resistance. Central adiposity is a known factor associated with
Glucose levels and insulin in clinical studies
Glucose metabolism is commonly impaired in patients with acute illness, even in non-diabetic patients. Van Vught and coworkers studied the relationship between admission glucose levels > 70 mg/dL and outcomes in 987 patients with sepsis.7 Glucose values were collected within the timeframe of 4 h before admission to 4 h after admission. Two hundred one patients had severe hyperglycemia defined as a glucose level ≥ 200 mg/dL, and these patients developed acute kidney injury and acute myocardial
Clinical studies managing glucose levels
The metabolic mechanisms that take place during a hyperglycemic state, such as muscle glycolysis and lipolysis, are indicators of poor outcomes in septic shock patients. These metabolic disturbances limit the body's host defenses against infection by inhibiting chemotactic factors for leukocytes, impairing phagocytosis, altering cytokine patterns with increased concentrations of the early proinflammatory cytokines, tumor necrosis factor-α, and interleukin (IL)-6, and reducing endothelial nitric
Conclusions
The available literature does not provide definitive answers to questions about the association between insulin levels and outcomes in patients with sepsis or septic shock. Several studies have reported that insulin levels are increased in patients with sepsis and septic shock. Limited information suggests that there is an immediate change in insulin sensitivity that varies over the first several days in patients with sepsis. C-peptide levels are higher in patients with sepsis, and the ratio of
References (44)
Insulin resistance is a two-sided mechanism acting under opposite catabolic and anabolic conditions
Med Hypotheses
(2016)- et al.
Sepsis uncouples serum C-peptide and insulin levels in critically ill patients with type 2 diabetes mellitus
Crit Care Resusc
(2019) - et al.
Acute insulin resistance following injury
Trends Endocrinol Metab
(2009) - et al.
Protection of hepatocyte mitochondrial ultrastructure and function by strict blood glucose control with insulin in critically ill patients
Lancet
(2005) - et al.
Association between mitochondrial dysfunction and severity and outcome of septic shock
Lancet
(2002) - et al.
Glucose metabolism and insulin therapy
Crit Care Clin
(2006) - et al.
Molecular mechanisms behind clinical benefits of intensive insulin therapy during critical illness: glucose versus insulin
Best Pract Res Clin Anaesthesiol
(2009) - et al.
Proteolysis in septic shock patients: plasma peptidomic patterns are associated with mortality
Br J Anaesth
(2018) - et al.
The effect of short-term hyperglycemia on the innate immune system
Am J Med Sci
(2016) Association between hyperglycemia and increased hospital mortality in a heterogeneous population of critically ill patients
Mayo Clin Proc
(2003)
Insulin resistance: review of the underlying molecular mechanisms
J Cell Physiol
Williams textbook of endocrinology
Insulin receptor isoforms and insulin receptor/insulin-like growth factor receptor hybrids in physiology and disease
Endocr Rev
What causes the insulin resistance underlying obesity?
Curr Opin Endocrinol Diabetes Obes
Recent advances in the relationship between obesity, inflammation, and insulin resistance
Eur Cytokine Netw
Admission hyperglycemia in critically ill sepsis patients: association with outcome and host response
Crit Care Med
Critical illness-induced dysglycaemia: diabetes and beyond
Crit Care
Intensive insulin therapy in critically ill patients
N Engl J Med
Insulin resistance as a prognostic indicator in severe sepsis, septic shock and multiorgan dysfunction syndrome
J Med Public Health
The role of insulin resistance in outcome of patients with multi organ dysfunction syndrome
J Med Sci Clin Res
Insulin resistance and beta cell function as prognostic indicator in multi-organ dysfunction syndrome
Metab Syndr Relat Disord
Pathophysiological aspects of hyperglycemia in children with meningococcal sepsis and septic shock: a prospective, observational cohort study
Crit Care
Cited by (0)
Conflicts: None.
Financial support: None.