Risks/Outcomes/PredictorsHyperglycemia in sepsis is a risk factor for development of type II diabetes
Introduction
Hyperglycemia is common during acute infection, particularly in patients with sepsis [1], as is in other critical illnesses and is often referred to as critical illness hyperglycemia (CIH). It may arise in patients with previously diagnosed diabetes or impaired glucose metabolism, or as a first manifestation of previously undiagnosed diabetes. However, it frequently occurs in patients who have normal glucose metabolism before and after the septic episode.
Increase of blood glucose during infection, as in other acute insults to the organism, is a part of adaptive response, mediated by inflammation and neuroendocrine mechanisms. Activation of hypothalamic-pituitary-adrenal axis in stress leads to release of cortisol, but stress response also increases secretion of other anti-insulin hormones: catecholamines, glucagon and growth hormone [2], [3]. Proinflammatory cytokines, predominantly interleukin-1 and tumor necrosis factor α, cause hyperglycemia and peripheral insulin resistance by promoting the same hormones, but also by altering insulin receptor signaling [4], [5], [6], [7], [8]. In muscle and fat cells, inflammation-mediated insulin resistance decreases glucose uptake, whereas in hepatocytes, it causes ongoing gluconeogenesis regardless of hyperglycemia and increased insulin release. In addition, despite hyperglycemia and peripheral insulin resistance insulin concentrations in sepsis may be normal or even decreased, due to suppression of pancreatic β cells caused by proinflammatory cytokines and stimulation of α receptors by catecholamines [9], [10]. All these mechanisms are physiologic responses to infection and are probably present in all patients with sepsis, but evident hyperglycemia is not present in all of them. It is most obviously associated with severity disease, and has been associated with unfavorable outcome in sepsis [1].
Hyperglycemia itself was shown to be harmful during critical illness. Tight glucose control during sepsis has been shown to be associated benefit in survival [11], [12], [13], [14] and is now a part of the Surviving Sepsis Campaign Guidelines [15].
The association between severity of illness, hyperglycemia and outcome is clear, but all patients with severe infections, even with organ failure, do not develop hyperglycemia and some will have increased blood glucose even in milder disease.
Our hypothesis therefore was that hyperglycemia in non-diabetic patients with sepsis is not only a marker of disease severity but is also a marker of latent disturbance in glucose metabolism and that it could be associated with increased risk of developing type 2 diabetes or impaired glucose metabolism in the period following recovery from sepsis.
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Patients and methods
This was a prospective, noninterventional single-center study. Adult patients with sepsis admitted to the medical intensive care unit (ICU), University Hospital Rebro during 5 years (July 1998-June 2003) with negative history for diabetes mellitus (DM), impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) were evaluated.
The following data were collected for all patients: age, sex, family history of diabetes, body mass index (BMI), serum cholesterol and triglyceride concentrations.
Hyperglycemia and severity of sepsis
During the 5 inclusion years, there were 1843 admissions to our ICU, 744 (40.3%) with sepsis (including severe sepsis and septic shock). There were 584 septic patients with no history of hyperglycemia or diabetes mellitus (Fig. 1) before the admission: 226 (38.7%) had mild sepsis, 276 (47.2%) severe sepsis, and 88 (15.1%) had septic shock.
Hyperglycemia was more frequent in patients with severe sepsis (n = 100, 36.2%) and septic shock (n = 40, 45.5%) than in mild sepsis (n = 60, 26.5%) (P =
Discussion
According to our results, patients with hyperglycemia during sepsis are at increased risk of developing type 2 diabetes mellitus or impaired glucose metabolism (IFG or IGT).
The results also confirm previously known fact that hyperglycemia is more frequent in more severe disease and that it is associated with higher mortality risk [1], [22], [23]. Glucose variability was not higher in more severe disease, but higher variability of glucose was observed in patients who did not survive. This result
Conclusion
Hyperglycemia in nondiabetic patients with sepsis is related to severity of illness and probably to an intrinsic disturbance of glucose metabolism. Hyperglycemia is associated with 4-fold risk for development of diabetes mellitus and double risk for development of IFG or IGT in the 5 years after septic episode. Patients with hyperglycemia in sepsis should be followed up as high-risk population for development of diabetes.
References (44)
Neuroendocrine pathobiology of chronic critical illness
Crit Care Clin
(2002)- et al.
Stress-induced hyperglycemia
Crit Care Clin
(2001) - et al.
Tumor necrosis factor-alpha inhibits insulin-induced increase in endothelial nitric oxide synthase and reduces insulin receptor content and phosphorylation in human aortic endothelial cells
Metabolism
(2002) Alterations in fuel metabolism in critical illness: hyperglycaemia
Best Pract Res
(2001)- et al.
Caloric intake in medical ICU patients: consistency of care with guidelines and relationship to clinical outcomes
Chest
(2003) - et al.
Stress-induced hyperglycemia in patients with severe sepsis: a compromising factor for survival
Am J Med Sci
(2008) - et al.
Impact of acute hyperglycemia during primary stent implantation in patients with ST-elevation myocardial infarction
J Cardiol
(2009) - et al.
American College of Endocrinology position statement on inpatient diabetes and metabolic control
Endocr Pract
(2004) - et al.
Blood insulin responses to blood glucose levels in high output sepsis and septic shock
Am J Surg
(1978) - et al.
Metabolic syndrome and insulin resistance significantly correlate with body mass index
Arch Med Res
(2008)
Glucose metabolism and insulin resistance in sepsis
Curr Pharm Des
The dynamic neuroendocrine response to critical illness
Endocrinol Metab Clin North Am
Inflammatory status and insulin resistance
Curr Opin Clin Nutr Metab Care
Mediators of cytokine-induced insulin resistance in obesity and other inflammatory settings
Curr Opin Clin Nutr Metab Care
Stress-hyperglycemia, insulin and immunomodulation in sepsis
Intensive Care Med
Low-dose interleukin 1 and tumor necrosis factor individually stimulate insulin release but in combination cause suppression
Eur J Endocrinol
Influence of diabetes and hyperglycaemia on infectious disease hospitalisation and outcome
Diabetologia
Hyperglycaemia and mortality in critically ill patients. A prospective study
Intensive Care Med
Intensive insulin therapy in the critically ill patients
N Eng J Med
Glycometabolic state at admission: important risk marker of mortality in conventionally treated patients with diabetes mellitus and acute myocardial infarction: long-term results from the Diabetes and Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) study
Circulation
Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2008
Intensive Care Med
APACHE II: a severity of disease classification system
Crit Care Med
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