Early diabetic nephropathy and endothelial dysfunction in children with type 1 diabetes mellitus

Diabetes mellitus is an established risk factor for early cardiovascular disease. The microvascular complications of type 1 diabetes are known to increase with duration of the disease. The extent of vascular disease in Type 1 DM may reflect duration of the disease and severity of chronic metabolic derangements. The aim of this study was to analyze the relation between the duration of diabetes and the microvascular complication markers such as microalbuminuria, vascular endothelial growth factor, angiopoietin-2, arterial stiffness and ambulatuar blood pressure monitoring (ABPM). Forty children with Type 1 DM attending the Pediatric Endocrinology Out-patient Clinic of Çukurova University and 40 healthy children were included in the study. Patients were divided into two subgroups: 20 children 5 to 9 years following the onset of diabetes were included in DM-1 group, and 20 children ≥10 years following the onset of diabetes were included in DM-2 group. All the children had 24 h urine microalbumine excretion, HbA1c level, renal function tests, lipid profile. All children also underwent 24 h blood pressure monitoring and all had Ang-2 and VEGF levels measured using ELISA test. Arterial stiffness was assessed with pulse wave analysis (PWA) and pulse wave velocity (PWV) using Vicorder device and carotis intima thickness was measured using an ultrasonogrophic device named Acuson. 24 h urine microalbumine excretion was higher in DM-1 and DM2 groups compared to controls (p=0,037, p=0,006 respectively). No significant difference was found in HbA1c levels between DM-1 and DM-2 groups. Systolic, diastolic and mean blood pressure of daytime, night time and 24 h z scores were found significantly higher in DM-1 and DM-2 groups compared to controls (p<0.001). Systolic and diastolic blood pressure loads (>%30) were significantly higher in DM-1 and DM-2 groups compared to controls. Mean cIMT was not higher in DM-1 and DM-2 group compared to controls. There was no significant difference between the groups regarding carotid distenbility, elasticity RAW and SDS, stifness RAW and SDS. Pulse wave velocity level was higher in DM-2 group compared to control (p=0.02). VEGF levels were found higher in DM-1 and DM-2 groups compared to controls (p<0.001). Ang-2 levels were higher in DM-2 group compared to controls (p<0.001). No significant difference was found in Ang-2 levels between DM-1 and control groups (p<0.5). There was a significant difference in Ang-2 levels between DM-1 and DM-2 groups (p=0,017). Significant positive correlation was found between Ang-2 and 24 h urinary microalbumine excretion. In this study, detection of hypertension in diabetic patients and significant higher levels of VEGF and Ang-2 levels show incipient microvascular complication and endothelial damage. 24 h urine microalbuminuria, higher blood pressure profile could be predictors of diabetic nephropathy in these children. Strict glycemic control are recommended for reducing the microvascular complication in diabetic children. Key words: Type 1 Diabetes Mellitus, microvascular complications, Ang-2, VEGF