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

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.

Keywords: C1q/TNF-related protein 1; CTRP1; ICU; adipokine; critical illness; diabetes; glucose metabolism; inflammation; metabolism; sepsis.

Figure 1

CTRP1 levels in critically ill patients and sepsis. (a) CTRP1 plasma concentrations, at time of admission to the ICU, were significantly elevated in critically ill patients (n = 218) compared with healthy controls (n = 66) (p < 0.001; U-Test). (b) CTRP1 levels are associated with the presence of sepsis (sepsis, n = 145; no sepsis, n = 73) (p = 0.006; U-Test). *: extreme outlier; ICU—intensive care unit; CTRP1—C1q/TNF-related protein 1.

Figure 2

CTRP1 levels in critically ill patients are not associated with disease severity and short-term mortality. (a) Patients with high disease severity (n = 147), as defined by an APACHE-II score above 10, are not associated with elevated plasma CTRP1, but show a tendency towards higher CTRP1 levels at ICU admission (p = 0.339; U-Test). (b) Patients that died during the course of ICU treatment (n = 49) are characterized by a tendency towards higher plasma CTRP1 concentrations already at ICU admission (p = 0.166; U-Test). APACHE—Acute Physiology And Chronic Health Evaluation; ICU—intensive care unit; CTRP1—C1q/TNF-related protein 1.

Figure 3

Impact of metabolic comorbidities on CTRP1 levels. CTRP1 plasma concentrations are significantly elevated in ICU patients with pre-existing type 2 diabetes (n = 150) (p = 0.004; U-test) (a). CTRP1 levels are not associated with obesity, as defined by a body-mass index (BMI) above 30 kg/m² (n = 55) (p = 0.219; U-Test (b) and r = 0.189, p = 0.007; Spearman rank correlation test (c). BMI—body mass index; ICU—intensive care unit; CTRP1—C1q/TNF-related protein 1.

Figure 4

CTRP1 levels correlate with renal function in critically ill patients. In the ICU cohort, CTRP1 correlates with markers of excretory renal function such as creatinine (a) and GFR-cystatin C (b). GFR—glomerular filtration rate.