Adiponectin, retinol-binding protein 4, and leptin in protracted critical illness of pulmonary origin

Abstract

IntroductionCritically ill patients requiring intensive care uniformly develop insulin resistance. This is most pronounced in patients with sepsis. Recently, several hormones secreted by adipose tissue have been identified to be involved in overall insulin sensitivity in metabolic syndrome-related conditions. However, little is known about these adipokines in critical illness.MethodsWe studied circulating levels of the adipokines adiponectin, retinol-binding protein 4 (RBP4), and leptin during critical illness, and the impact of intensive insulin therapy, a therapy shown to affect insulin sensitivity, in serum samples from prolonged critically ill patients with a respiratory critical illness (n = 318). For comparison, we studied healthy subjects (n = 22) and acutely stressed patients (n = 22).ResultsDuring acute critical illness, circulating levels of adiponectin, RBP4, and leptin were low. Patients with sepsis had lower levels of leptin and RBP4 than did nonseptic patients. When critical illness was sustained, adipokine levels returned to normal reference values. Insulin therapy enhanced adiponectin, blunted the rise of RBP4, and did not alter leptin levels.ConclusionsAcute critical illness is associated with immediate, but transiently low serum adipokine levels. Adiponectin and RBP4 are associated with altered insulin resistance in critical illness.

Adipocytokines in Severe Sepsis and Septic Shock

“…In the same study low adiponectin serum concentrations at admission to ICU have been found as a positive prognostic indicator for ICU and overall survival in contrast to the above mentioned theory of low adiponectin levels worsening the outcome of critically ill patients [72]. Interestingly, no correlation of adiponectin with cytokines or mediators of inflammation have been reported in critically ill patients [64,72]. The mechanisms of adiponectin excretion and biodegradation in critical disease are presently unclear.…”

“…Yousef and colleagues also reported increased values for IL-6, CRP, TNF-α and leptin at admission to ICU, with leptin threshold values of 38 µg/l for distinguishing between SIRS and sepsis [7]. Controversially, among other studies, a study from Denmark revealed low leptin levelsand also low adiponectin and RBP4 levels -at admission to the ICU, possibly due to an acute stress response [64]. The absence of increasing leptin levels in these studies may be due to the short duration of the experiments, given that a delay is needed to observe an increase of leptin following a LPS-stimulation [65].…”

“…In critical disease RBP4 serum levels have been found decreased compared to healthy controls, independent of the origin of critical illness [64,92]. During the course of disease, serum levels normalized with resolving critical illness [64].…”

“…Glucocorticoids, inflammation, and oxidative stress -commonly associated with critical disease -are known for reducing adiponectin synthesis [81]. Matching these facts, some studies reported low adiponectin levels in patients with critical disease of pulmonary origin and also in rats with sepsis (without analyzing the impact of the measured low values on mortality or outcome) [64,82]. Nevertheless, there are conflicting data concerning the role of adiponectin in critical illness.…”

“…During the course of disease, serum levels normalized with resolving critical illness [64]. Langouche and colleagues hypothesized that reduced synthesis or increased removal might be the reason for the decreased serum levels.…”