Toll/Interleukin-1 receptor member ST2 exhibits higher soluble levels in type 2 diabetes, especially when accompanied with left ventricular diastolic dysfunction

Abstract

BackgroundSoluble ST2, a member of the of the Toll/IL-1 superfamily, is a novel biomarker with exceptional predictive value in heart failure and myocardial infarction- related mortality as well as in acute dyspneic states. Soluble ST2 is considered a decoy receptor of IL 33 that blocks the protective effects of the cytokine in atherosclerosis and cardiac remodeling. In the present study we investigated the differences in the levels of soluble ST2, BNP and hs-CRP between healthy controls and patients with type 2 diabetes with and without left ventricular diastolic dysfunction. A secondary aim was to investigate correlations between sST2 and other biomarkers of type 2 diabetes, such as HbA1c.Methods158 volunteers were recruited and underwent a complete Doppler-echocardiographic evaluation of both systolic & diastolic cardiac function. All subjects with ejection fraction < 50% were excluded. The study population was divided in 4 groups as follows: A: 42 healthy controls, B: 18 subjects without diabetes with LVDD, C: 48 patients with type 2 diabetes without LVDD & D: 50 patients with type 2 diabetes & LVDD. ELISA technique was performed to measure sST2 levels. Statistical analysis was performed with Kruskal-Wallis & Mann-Whitney test (continuous variables), chi squared & Fischer exact test (discrete variables), Spearman coefficient (univariate analysis) and step-wise backward method (multivariate analysis).ResultsPatients with type 2 diabetes with (p < 0.001) or without LVDD (p = 0.007) had higher serum ST2 levels compared to healthy controls, state found also for hs-CRP levels but not for the corresponding BNP levels (p = 0.213 & p = 0.207 respectively). Patients with type 2 diabetes & LVDD had higher serum ST2 in relation to diabetic patients without LVDD (p = 0.001). In multivariate analysis HbA1c positively and independently correlated with sST2 levels in both groups of patients with type 2 diabetes.ConclusionsPatients with type 2 diabetes exhibit higher sST2 levels compared to healthy controls. The presence of LVDD in patients with type 2 diabetes is associated with even higher sST2 levels. A significant correlation between glycemic control and sST2 levels was also revealed.

Regulation of De Novo Adipocyte Differentiation Through Cross Talk Between Adipocytes and Preadipocytes

“…On one hand, IL-33 has been considered to prevent adipose tissue inflammation and thus reduce metabolic complications (38,41). However, other studies have linked increased Il-33 levels to morbid obesity and the development of diabetes (40,41). Since IL-33 has been mainly implicated in immune cell function, our findings might provide a link between inflammation and adipocyte differentiation.…”

Emerging role of interleukin‐33 in autoimmune diseases

“…The above evidence suggests that manipulating IL‐33 expression may be a useful therapeutic strategy for treating or preventing T2D in obese patients. In fact, high levels of sST2 are detected in T2D patients compared with healthy controls, and the levels are even higher in those with left ventricular diastolic dysfunction . Furthermore, sST2 levels are positively and independently correlated with glycaemic controls in T2D and the authors proposed that chronic inflammation most likely establishes the basis of increased sST2 levels.…”

Soluble ST2 Levels and Left Ventricular Structure and Function in Patients With Metabolic Syndrome

“…Recently, sST2 has been reported to be increased in patients with heart failure, myocardial infarction, hypertension, severe obesity, and diabetes [91011121314]. sST2 emerged as a prognostic biomarker for both nonfatal cardiac events and mortality in high-risk patients [15].…”