Concentration of diabetes-associated autoantibodies against islet autoantigens (IA-2A, GADA, IAA), levels of basal and postprandial glycemia, and secretory state of basal and stimulated C-peptide in the preclinical period of type 1 diabetes development in children and adolescents as immunological, metabolic and hormonal predictors of the clinical onset of the disease

Abstract

Materials and methods. Based on clinical and immunological studies, in this study, we present data on the establishment of mechanisms that are responsible for the development of early and late pre-clinical stages of the type 1 diabetes (T1D), obtained by studying diabetes-associated autoantibodies (DAAb) and the levels of basal and postprandial glycemia, and C-peptide secretion at the preclinical stage of T1D development in children and adolescents. Results. As a result we were able to form a group of marker-positive children with a genetic predisposition and an increased predicted risk of developing the diease. A total of 474 practically healthy normoglycemic children and adolescents aged 7 to 18 years were examined. An elevated titre of DAAb, mainly GADA and IA-2A was found in 94 (25.68 %) of 366 children with a genetic predisposition for at least of two determinants of DAAb, and the clinical onset of T1D manifesting in 68 (72.34 %) of them from 6 months to 15 years (30.9 ± 3.2 months). The formula of combined occurrence and values of simultaneously elevated titres of DAAb against islet autoantigens, namely, IA-2A + GADA, which is a predictor of the duration of the preclinical stage of T1D, was determined. Conclusions. It was established that the early preclinical development of T1D in DAAb + children was characterized by the presence of dysglycemia in the form of elevated glycemia 2 hours after the glucose tolerance test and a steady decrease in the secretion of stimulated C-peptide; additionally, dysglycemia was jointed as impaired fasting glycemia, and there was a decrease in both basal and stimulated secretions of C peptide, indicating the depletion of the potential of pancreatic beta-cells. Key words: type 1 diabetes (T1D), children and adolescents, diabetes-associated autoantibodies (DAAb), autoantibodies against glutamic acid decarboxylase (GADA), autoantibodies against tyrosine phosphatase (IA-2A), basal and postprandial glycemia, basal and stimulated C-peptide. For citation: Tronko MD, Mankovskyi BM, Popova VV, Zak KP. Concentration of diabetes-associated autoantibodies against islet autoantigens (IA-2A, GADA, IAA), levels of basal and postprandial glycemia, and secretory state of basal and stimulated C-peptide in the preclinical period of type 1 diabetes development in children and adolescents as immunological, metabolic and hormonal predictors of the clinical onset of the disease. Journal of the National Academy of Medical Sciences of Ukraine. 2019;25(3):285–95