Microvascular and hypoxic disorders in children with diabetic nephropathy
Background: In diabetes mellitus type I (T1D) progression of cardio-renal disorders, i.e. arterial hypertension and its complications, diabetic nephropathy (DN), is still the most important side-effect. Search of the mechanisms underlying these damages is on priority list. Vitamin D deficiency identified as a common metabolic/endocrine disorder worldwide in health and diseases. There are data about the role of Vitamin D in T1D in adults. However, this issue remains to be open in pediatric practice.
Aim: To study the levels of Vitamin D, Endothelin-1 and primary cellular hypoxia markers in children with T1D and DN and to find out the network of these markers inter-relation.
Material and Methods: Thirty six (36) children T1D aged 6 to 17 years hospitalized in Endocrinology unit in Children Clinical Hospital №6 (Kyiv, Ukraine) studied. Vitamin D3 levels measured using ELISA assay and commercially available kit (Vitamin D3 (human) ELISA kit (BioVision, USA). Endothelin-1 levels measured using ELISA assay and commercially available Endothelin-1 ELISA kit (Abcam, USA). The O2-Hb dissociation rate studied spectrophotometrically. Results processed using STATISTICA 6.0 and non-parametric statistical method (Mann-Whitney test).
Results: In our study normal level, insufficiency and deficiency of the Vitamin D defined as - ≥30ng/mL, 21-29ng/mL and ≤20ng/mL, respectively. All patients included into the study during the period September-May. We show that the most prominent Vitamin D3 deficiency detected in the group of patients with diabetic nephropathy (DN). In control group Vitamin D3 was detected at level 35.68±1.56ng/mL, in patients with T1D – 32.37±5.1ng/mL, in patients with DN – 19.39±1.76ng/mL (р<0.01 as compared to control group). Analysis of the Vitamin D3 levels and the disease course show negative correlation (R=-0.79, р<0.001). In all children the hemoglobin affinity to O2 molecule studied based on Sore peak analysis. Control group show this index at level 3.05±0.23 a.u., children with T1D – 3.61±0.25 a.u. (p<0.05), patients with DN 1.76±0.27 a.u. (p<0.01, compared to control group value). In all children with T1D and DN increased level of ET-1 measured.
Conclusion: Our data show the prominent deficiency of Vitamin D in T1D patients and patients with DN, increased ET-1 level (a potent vasoconstrictor peptide), and reduction of the O2-Hb dissociation rate. We hypothesize that Vitamin D deficiency is a result of toxic effect of glucose. Increased ET-1 in all patients is a sign of early microvascular changes and resistant vessels damage leading to DN progression and arterial hypertension. All mentioned above changes accompanied by reduced O2-Hb dissociation as a result of increased level of HbA1C and may be a reason of cellular hypoxia.