Soluble Endoglin Level Increase Occurs Prior to Development of Subclinical Structural Vascular Alterations in Diabetic Adolescents

Abstract

Objective:Soluble endoglin (S-endoglin) has been implicated as a potential marker of endothelial dysfunction (ED) and was reported to be elevated in diabetic adults, correlating with the severity of diabetic vasculopathy. However, circulating S-endoglin and its association with other markers of ED have not been formerly analyzed in the first decade of diabetes onset in adolescents with type 1 diabetes mellitus (T1DM).Methods:Fifty-eight adolescents with moderately/poorly controlled T1DM were included in this study and twenty-nine healthy adolescents served as controls. The diabetic group was divided into two groups based on the presence of microalbuminuria, as the microalbuminuria group (n=15) and the normoalbuminuria group (n=43). Functional vascular alterations were evaluated by measuring serum S-endoglin and plasma nitric oxide (NO) concentrations, the flow-mediated dilatation (FMD) of the brachial artery. Carotid intima media thickness (CIMT) was measured for evaluation of structural vascular alterations.Results:The S-endoglin and NO levels of both microalbuminuria and normoalbuminuria groups were higher than those of the control group (for S-endoglin, p=0.047 and p<0.001; for NO, p=0.004 and p=0.006, respectively). The FMD percent was lower in the microalbuminuria group compared to the normoalbuminuria and control groups (p=0.036 and p=0.020, respectively). There were negative correlations between S-endoglin concentration and FMD percent (r=-0.213, p=0.051) and between serum S-endoglin concentration and albumin excretion rate (r=-0.361, p=0.005). No significant differences were found in CIMT among any of the groups (p=0.443).Conclusion:In adolescents with T1DM, S-endoglin concentrations might increase in parallel to the deterioration in endothelial function before subclinical structural vascular alterations become evident.

Soluble endoglin regulates expression of angiogenesis-related proteins and induction of arteriovenous malformations in a mouse model of hereditary hemorrhagic telangiectasia

“…Abnormal levels of sEng are found in several endothelium-related pathological conditions, including pre-eclampsia ( Venkatesha et al, 2006 ; Oujo et al, 2013 ; Gregory et al, 2014 ), atherosclerosis, hypercholesterolemia ( Blann et al, 1996 ; Blaha et al, 2008 ; Rathouska et al, 2015 ), diabetes mellitus ( Blázquez-Medela et al, 2010 ; Ceriello et al, 2015 ; Emeksiz et al, 2016 ), hypertension ( Blázquez-Medela et al, 2010 ), diabetic retinopathy ( Malik et al, 2005 ), coronary artery disease ( Li et al, 2000a ; Ikemoto et al, 2012 ; Saita et al, 2017 ), HHT1 ( Letarte et al, 2005 ; Botella et al, 2015 ), acute myocardial infarction ( Cruz-Gonzalez et al, 2008 ) and cancer ( Li et al, 2000b ; Bernabeu et al, 2009 ). In many of these diseases, the deregulated levels of sEng in plasma, serum or urine from patients have been postulated to be a reliable biomarker for severity correlation and prognosis.…”

Novel Biomarkers for Evaluation of Endothelial Dysfunction

“…108 Also, in a cross-sectional study with adolescents with type 1 diabetes mellitus, a relative decline in sEng levels was observed with the development of microalbuminuria, an indicator of generalized ED, supporting the hypothesis that increased sEng may be an early indicator of vascular alterations. 124 Another study showed that patients with acute myocardial infarction (AMI) had lower levels of sEng than healthy individuals and that decreased sEng levels were associated with a higher CV mortality. 125 These authors argued that this phenomenon may be related to a decrease in membrane endoglin levels, especially L-endoglin, which is thought to be related to a stable atherosclerotic plaque phenotype.…”

Endothelin‐1 levels are decreased in pediatric Type 1 diabetes and negatively correlate with the carotid intima media thickness

“…Elevated cIMT in patients with T1D is supported by several studies in the pediatric population, demonstrating impairments to occur relatively early in the course of the disease, although this is not a universal finding. 10,[16][17][18][19][20] Moreover, the results of the Epidemiology of Diabetes Interventions and Complications study found no significant differences in cIMT between the diabetic cohort and nondiabetic controls, including young adults with a mean disease duration of about 14 years. 21 Similarly conflicting results, regarding associations of cIMT with disease duration can be found.…”