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

Abstract

Introduction: Critically 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.

Methods: We 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).

Results: During 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.

Conclusions: Acute critical illness is associated with immediate, but transiently low serum adipokine levels. Adiponectin and RBP4 are associated with altered insulin resistance in critical illness.

Trial registration: ClinicalTrials.gov NCT00115479.

Figure 1

Circulating adipokines during critical illness. (a-c) Impact of acute illness: Results from healthy volunteers, patients not critically ill undergoing elective surgery, and critically ill patients on admission to the ICU are presented as box plots (boxes are medians and interquartile ranges; whiskers are 10^th and 90^th percentiles). (d-f) Critically ill patients who received CIT (white bars) or IIT (gray bars). Reference values (mean ± SEM) of healthy controls are indicated by two horizontal dotted lines. Adm = admission day; D5 = day 5; D10 = day 10; LD = the last day of ICU stay; ICU = intensive care unit. Data are presented as mean ± SEM. *P ≤ 0.05; **P ≤ 0.01. For statistical analysis, we subtracted corresponding admission-day values, and for leptin, we used log-transformed data as indicated on the figure.