Elevated CTRP1 Plasma Concentration Is Associated with Sepsis and Pre-Existing Type 2 Diabetes Mellitus in Critically Ill Patients.

Eray Yagmur,Ralf Weiskirchen,Alexander Koch,Christian Trautwein,Ger H Koek,Frank Tacke,David Buergerhausen

doi:10.3390/jcm8050661

Abstract

The adipokine family of C1q/TNF-like proteins (CTRP) plays a critical role in regulating systemic energy homeostasis and insulin sensitivity. It is involved in pathophysiological processes including inflammation and insulin-resistant obesity. Sepsis is associated with metabolic alterations and dysregulated adipokines, but the role of CTRP1 in critical illness and sepsis is unclear. We investigated CTRP1 plasma concentrations in 145 septic and 73 non-septic critically ill patients at admission to the medical intensive care unit (ICU) in comparison to 66 healthy controls. We also assessed associations of CTRP1 with clinical characteristics, adipokine levels, metabolic and inflammatory parameters. CTRP1 plasma concentration was significantly elevated in critically ill patients compared to healthy subjects. CTRP1 levels were significantly higher in ICU patients with sepsis. CTRP1 correlated strongly with markers of inflammatory response, renal function, liver damage and cholestasis. Furthermore, CTRP1 levels were higher in ICU patients with type 2 diabetes mellitus, and correlated with HbA1c and body mass index. This study demonstrates significantly elevated levels of CTRP1 in critically ill patients, particularly with sepsis, and links circulating CTRP1 to inflammatory and metabolic disturbances.

Highlights

The highly conserved family of secreted C1q/TNF-relatedproteins (CTRP) is a paralogue of adiponectin with diverse functions in regulating metabolism and immunity [1,2,3,4]
CTRP1 with BMI, but weak evidence, we found that CTRP1 in critical illness is not associated with a variety of established biomarkers of energy substrate metabolism or diabetes-related cytokines such as insulin, leptin, leptin receptor, ghrelin, adiponectin, resistin or retinol-binding protein 4 (RBP4)
Prospectively enrolled study, CTRP1 levels were significantly elevated in critically ill patients and were associated with inflammation and sepsis as well as diabetes and metabolic disturbances

Summary

Introduction

The highly conserved family of secreted C1q/TNF-related (glyco-)proteins (CTRP) is a paralogue of adiponectin with diverse functions in regulating metabolism and immunity [1,2,3,4]. It is well known that infectious and inflammatory diseases such as sepsis and systemic inflammatory response syndrome are accompanied by metabolic alterations such as insulin resistance or dysregulated adipokines [13]. The stimulation of human vascular smooth muscle cells by CTRP1 results in upregulated expression of pro-inflammatory cytokines such as interleukin 6 (IL-6), monocyte chemoattractant protein 1 (MCP1) and intracellular adhesion molecule 1 (ICAM1) [19]. These genes were proposed as potential key modulators regarding the function of CTRP1 in inflammatory diseases [19]. We assessed plasma CTRP1 concentration in a large cohort of critically ill medical patients admitted to the intensive care unit (ICU) in order to investigate the diagnostic and clinical relevance of circulating CTRP1

Experimental Section

Results

Conclusions