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

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          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.

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          Most cited references27

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          Retinol-binding protein 4 and insulin resistance in lean, obese, and diabetic subjects.

          Insulin resistance has a causal role in type 2 diabetes. Serum levels of retinol-binding protein 4 (RBP4), a protein secreted by adipocytes, are increased in insulin-resistant states. Experiments in mice suggest that elevated RBP4 levels cause insulin resistance. We sought to determine whether serum RBP4 levels correlate with insulin resistance and change after an intervention that improves insulin sensitivity. We also determined whether elevated serum RBP4 levels are associated with reduced expression of glucose transporter 4 (GLUT4) in adipocytes, an early pathological feature of insulin resistance. We measured serum RBP4, insulin resistance, and components of the metabolic syndrome in three groups of subjects. Measurements were repeated after exercise training in one group. GLUT4 protein was measured in isolated adipocytes. Serum RBP4 levels correlated with the magnitude of insulin resistance in subjects with obesity, impaired glucose tolerance, or type 2 diabetes and in nonobese, nondiabetic subjects with a strong family history of type 2 diabetes. Elevated serum RBP4 was associated with components of the metabolic syndrome, including increased body-mass index, waist-to-hip ratio, serum triglyceride levels, and systolic blood pressure and decreased high-density lipoprotein cholesterol levels. Exercise training was associated with a reduction in serum RBP4 levels only in subjects in whom insulin resistance improved. Adipocyte GLUT4 protein and serum RBP4 levels were inversely correlated. RBP4 is an adipocyte-secreted molecule that is elevated in the serum before the development of frank diabetes and appears to identify insulin resistance and associated cardiovascular risk factors in subjects with varied clinical presentations. These findings provide a rationale for antidiabetic therapies aimed at lowering serum RBP4 levels. Copyright 2006 Massachusetts Medical Society.
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            Weight reduction increases plasma levels of an adipose-derived anti-inflammatory protein, adiponectin.

            Adiponectin, an adipose tissue-specific plasma protein, was recently revealed to have anti-inflammatory effects on the cellular components of vascular wall. Its plasma levels were significantly lower in men than in women and lower in human subjects with obesity, type 2 diabetes mellitus, or coronary artery disease. Therefore, it may provide a biological link between obesity and obesity-related disorders such as atherosclerosis, against which it may confer protection. In this study, we observed the changes of plasma adiponectin levels with body weight reduction among 22 obese patients who received gastric partition surgery. A 46% increase of mean plasma adiponectin level was accompanied by a 21% reduction in mean body mass index. The change in plasma adiponectin levels was significantly correlated with the changes in body mass index (r = -0.5, P = 0.01), waist (r = -0.4, P = 0.04) and hip (r = -0.6, P = 0.0007) circumferences, and steady state plasma glucose levels (r = -0.5, P = 0.04). In multivariate linear regression models, the increase in adiponectin as a dependent variable was significantly related to the decrease in hip circumference (beta = -0.16, P = 0.028), after adjusting body mass index and waist circumference. The change in steady state plasma glucose levels as a dependent variable was related to the increase of adiponectin with a marginal significance (beta = -0.92, P = 0.053), after adjusting body mass index and waist and hip circumferences. In conclusion, body weight reduction increased the plasma levels of a protective adipocytokine, adiponectin. In addition, the increase in plasma adiponectin despite the reduction of the only tissue of its own synthesis suggests that the expression of adiponectin is under feedback inhibition in obesity.
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              Subcutaneous and Visceral Adipose Tissue: Their Relation to the Metabolic Syndrome

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                Author and article information

                Journal
                Crit Care
                Critical Care
                BioMed Central
                1364-8535
                1466-609X
                2009
                9 July 2009
                : 13
                : 4
                : R112
                Affiliations
                [1 ]Department of Intensive Care Medicine, Katholieke Universiteit Leuven, Herestraat 49, 3000 Leuven, Belgium
                [2 ]The Medical Research Laboratories, Clinical Institute, Aarhus University Hospital, Nørrebrogade 42-44, 8000 Aarhus, Denmark
                [3 ]Immunoendocrine Research Unit, Medicial Department M, Aarhus University Hospital, Norrebrogade 42-44, 8000 Aarhus, Denmark
                Article
                cc7956
                10.1186/cc7956
                2750156
                19589139
                eb3b62f2-d7fa-48d7-87ad-1e68024bcb0a
                Copyright ©2009 Langouche et al.; licensee BioMed Central Ltd.

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium provided the original work is properly cited.

                History
                : 6 March 2009
                : 17 April 2009
                : 5 May 2009
                : 9 July 2009
                Categories
                Research

                Emergency medicine & Trauma
                Emergency medicine & Trauma

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