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

Abstract

Better understanding of the timeline and risk factors for the appearance of complications in pediatric Type-1-diabetes is key for developing prevention strategies. We studied endothelial markers and their determinants in adolescents with Type-1-diabetes at different time points from diagnosis. A cross-sectional study of 58 adolescents, mean age 15.0± 2.4 years; 20 with recent-onset Type-1-diabetes, 20 with over 7 years of Type-1-diabetes and 18 controls. Clinical and biochemical data were collected. Fingertip arterial reactive hyperemia (EndoPAT) and carotid intima-media-thickness (cIMT) were measured to assess endothelial function and structure. Compared to controls, individuals with prolonged Type-1-diabetes had higher mean cIMT (0.49 ± 0.07 mm vs. 0.43 ± 0.05 mm p= 0.021) and maximal cIMT (0.61 ± 0.08 mm 0.52 ± 0.08 mm, p= 0.025). Endothelin-1 levels were significantly lower in subjects with prolonged Type-1-diabetes (1.2± 1.0pg/ml) compared to controls (3.0± 1.7, p= 0.008 pg/ml); they negatively correlated with the mean cIMT (c= -0.291, p= 0.031) and mean 6 months hemoglobin A1c (c= -0.301, p= 0.022) and positively correlated with mean c-peptide levels (c= 0.356, p= 0.006) and the weekly exercise time (c= 0.485, p< 0.001). Endothelin-1 levels did not correlate with EndoPAT results. Our results suggest that the early years after the diagnosis of Type-1-diabetes are an important window for prevention of arterial damage in the pediatric population. The trajectories of relationships of Endothelin-1 with metabolic and vascular measures were opposite from the anticipated, yet consistent. Endothelin-1 related indirectly to adverse measures and directly to favorable measures. Decreased Endothelin-1 levels might reflect early stages in endothelial impairment in Type-1-diabetes, yet its' exact role in the development of complications is yet to be unraveled.