Analysis of Apoptotic, Clinical, and Laboratory Parameters in Type 1 Diabetes and Early Diabetic Nephropathy: Clustering and Potential Groups Evaluation for Additional Therapeutic Interventions

Abstract

Objective: Type 1 diabetes (T1D) is one of the most prevalent chronic illnesses diagnosed in childhood. Diabetic nephropathy (DN) is one of the commonest complication of T1D. Therefore the development of specific treatment that arrests progression of DN based on an individual approach would be beneficial. Analysis of criteria of apoptosis, and clinical, and laboratory characteristics in T1D and early DN in the framework of clustering may be helpful in the identification of potential groups for additional therapeutic interventions. Methods: A survey of 104 children (62 males, 42 females) with T1D and DN aged 2 to 17 years in the Endocrinology unit of Clinical Pediatric Hospital No 6 (Kyiv, Ukraine) was performed. Clinical data (age, gender, disease duration, blood pressure), conventional laboratory markers including complete blood count, serum cholesterol, hemoglobin A1c (Hb1Ac), glomerular filtration rate (GFR), and microalbuminurea (MAU), and markers of apoptosis (BcL-xL, caspase-3) and transcriptional factor HIF-1alfa were analyzed. Results: A cluster group in T1D children was characterized by somewhat higher number of platelets (PLT) - 344.9±7.88·109/L, increased GFR up to hyperfiltration level 124.5±8.86 mL/min/1.73 m2 and decreased anti-apoptotic defense - BcL-xL 144.9±2.35 a.u. was identified. Children with DN may be divided into three groups based on age, body mass index, systolic blood pressure, PLT count, erthyrocyte sedimentation rate, albumin/globulin ratio, serum cholesterol, Hb1Ac, number of diabetic ketoacidosis (DKA) episodes, GFR, MAU, HIF-1alfa, Bcl-xL, caspase-3 levels. Among children with early DN a cluster characterized by the following parameters was found: PLT count - 311.±12.05·109/L, frequency of DKA episodes - 4.82±0.26 episodes/year, MAU - 112.0±10.12 mm/24 h, HIF - 200.5±3.49a.u., BcL-xL - 128.8±3.1 a.u., and caspase-3 - 159.6±5.5 a.u. Conclusion: Thus, we hypothesize that T1D pediatric patients with increased PLT count, hyperfiltration and reduced anti-apoptotic defense may represent a group for additional therapeutic interventions, such as antioxidants along with stndard therapies to achieve optimal glycemic control. Within the DN group there was a sub-group with somewhat increased PLT count, high frequency of DKA episodes/year, high MAU, prominent increase in HIF level, prominent disturbances in apoptosis controlling factors BcL-xL and caspase-3 tht may require additional therapeutic interventions, again including antioxidants, but may additionally benefit from anti-apoptotic effectors along with optimal glycemic control, and management of hypertension and albuminuria.