Predictors of microvascular complications in children and adolescents with type I diabetes mellitus

ABSTRACT

Diabetes mellitus is characterized by microangiopathy and increased angiogenic response. Several angiogenic factors are involved in vascular endothelial growth. This work was designed to study serum levels of angiogenic factors vascular endothelial growth factor [VEGF], basic fibroblast growth factor [bFGF], angiogenin and transforming growth factor-beta 1 [TGF-beta1] and their relationship to metabolic control in children and adolescents with type I diabetes mellitus and to evaluate whether these angiogenic factors can predict and identify cases at greater risk to develop diabetic retinopathy or persistent microalbuminuria in a follow-up period of 12 months. The present study included 20 type I diabetic cases aged 6-18 years and 15 healthy controls. Diabetic cases were subjected to detailed history taking, clinical examination, fundus examination, electroretinography [ERG] and repeated estimation of glycosylated hemoglobin [HbA1C%] and fasting blood glucose in addition to urinary albumin excretion [UAE] ug/minute/1.73m[2] in repeated 24 hours collection of urine. These data were collected at the baseline [at the beginning of the study] and after 12 months follow-up period. Baseline investigations included the determination of blood urea, serum creatinine and assessment of serum angiogenic factors VEGF, bFGF, angiogenin and TGF- beta1 by ELISA. At the beginning of the study, diabetic cases had significantly higher serum levels of VEGF, bFGF and angiogenin and significantly lower oscillatory potentials amplitude [Ops] than the control group. When diabetic cases were followed up for 12 months, 4/20 cases developed background retinopathy in fundus examination and 5/20 developed incipient nephropathy [persistent microalbuminuria] Development of microvascular complications was associated with significantly higher HbA1C%, serum VEGF, bFGF and angiogenin than uncomplicated cases. Furthermore, cases with diabetic retinopathy had significantly higher UAE and significantly lower baseline Ops than those without. Angiogenic factors as VEGF, bFGF and angiogenin and ERG examination could be used as predictors for identification of diabetic cases at high risk to develop diabetic retinopathy with a sensitivity of 75-100% and specificity of 81.25-93.75% and in prediction of incipient diabetic nephropathy with a sensitivity of 60-100% and a specificity of 86.67-93.33%. Angiogenic factors were correlated with HbA1C% and repeated blood glucose. The medical management of diabetes mellitus should be focused not only on metabolic control but also on measurement of angiogenic factors and ERG examination to predict cases at high risk of microvascular complications for early and more effective intervention that may include in the future antagonists to angiogenic factors