Serum Levels of TWEAK and Scavenger Receptor CD163 in Type 1 Diabetes Mellitus: Relationship with Cardiovascular Risk Factors. A Case-Control Study

Abstract

ObjectiveTo test the usefulness of serum concentrations of tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) and soluble scavenger receptor CD163 (sCD163) as markers of subtle inflammation in patients with type 1 diabetes mellitus (T1DM) without clinical cardiovascular (CV) disease and to evaluate their relationship with arterial stiffness (AS).MethodsSixty-eight patients with T1DM and 68 age and sex-matched, healthy subjects were evaluated. Anthropometrical variables and CV risk factors were recorded. Serum concentrations of sTWEAK and sCD163 were measured. AS was assessed by aortic pulse wave velocity (aPWV). All statistical analyses were stratified by gender.ResultsT1DM patients showed lower serum concentrations of sTWEAK (Men: 1636.5 (1146.3–3754.8) pg/mL vs. 765.9 (650.4–1097.1) pg/mL; p<0.001. Women: 1401.0 (788.0–2422.2) pg/mL vs. 830.1 (562.6–1175.9) pg/mL; p = 0.011) compared with their respective controls. Additionally, T1DM men had higher serum concentrations of sCD163 (285.0 (247.7–357.1) ng/mL vs. 224.8 (193.3–296.5) ng/mL; p = 0.012) compared with their respective controls. sTWEAK correlated negatively with aPWV in men (r = −0.443; p<0.001). However, this association disappeared after adjusting for potential confounders. In men, the best multiple linear regression model showed that the independent predictors of sTWEAK were T1DM and WHR (R2 = 0.640; p<0.001). In women, T1DM and SBP were the independent predictors for sTWEAK (R2 = 0.231; p = 0.001).ConclusionsTWEAK is decreased in T1DM patients compared with age and sex-matched healthy subjects after adjusting for classic CV risk factors, although sTWEAK levels may be partially influenced by some of them. Additionally, T1DM men have higher serum concentrations of sCD163. These results point out an association between the inflammatory system and CV risk in T1DM.

Soluble TWEAK levels predict the presence of carotid atherosclerotic plaques in subjects free from clinical cardiovascular diseases

“…We observed a gradual decrease in sTWEAK values in parallel with an increment in cardiovascular risk factors. This is in agreement with previous studies in which sTWEAK plasma levels were diminished in patients with type 1 [29] or type 2 diabetes mellitus [12] and hypertension [30]. In addition, we also observed that sTWEAK concentrations were independently and negatively correlated with c-IMT in the whole population.…”

The Relationship between Plasma Soluble Tnf-like Weak Inducer of Apoptosis Level and Inflammatory Markers in Patients with Type 2 Diabetes Mellitus

“…When groups were considered separately, RAS blockers did not have any effect on sTWEAK, TNF-a, IL-I and hsCRP levels in Group 2 and Group 3. The mean TNF-a level was lower in patients given an RAS blocker in Group 1. sTWEAK levels were found to be negatively correlated with the presence ofDM, smoking history, systolic and diastolic blood pressure, fasting plasma glucose, HbA Ic and IL-6 in type-I diabetic patients (15). We detected no relationship between sTWEAK levels and fasting plasma glucose and HbA1)evels in any of the study groups.…”

The role of tumor necrosis factor-like weak inducer of apoptosis in atherosclerosis via its two different receptors

“…CD163 is a marker for anti-inflammatory activity in macrophages (57) and is potentially a newly identified receptor for TWEAK, as reported previously (18,21). Increasing in vivo and in vitro evidence suggests that the interaction between TWEAK and CD163 may affect the development of atherosclerosis and related diseases (19,20,(57)(58)(59)(60).…”

“…Additionally, the TWEAK/Fn14 combination may become a novel target of interference in atherosclerosis development. As for CD163, in addition to its potential diagnostic uses in atherosclerosis-related diseases, it is also an interesting candidate for medical therapy (19,57,58,60). This is because CD163, as an example of the atheroprotective intraplaque population, eliminates free-Hb and releases a large quantity of anti-inflammatory mediators via activating downstream pathways (62,64).…”