Алгоритм доклинической диагностики сахарного диабета 1-го типа как основа для создания Реестра ДААт-позитивных детей и подростков Украины с прогнозированным развитием заболевания

Ключові слова

type 1 diabetes, children and adolescents, diabetes-associated autoantibodies (DAA), glutamic acid decarboxylase autoantibodies (GADA), tyrosine phosphatase protein (IA‑2A), cytokines, basal and postprandial glycemia, basal and stimulated C-peptide.

Як цитувати

Tron’ko, M., Zak, K., & Popova, V. (2019). Алгоритм доклинической диагностики сахарного диабета 1-го типа как основа для создания Реестра ДААт-позитивных детей и подростков Украины с прогнозированным развитием заболевания. Ендокринологія, 24(3), 203-216. https://doi.org/10.31793/1680-1466.2019.24-3.203


Aim — The establishment of mechanisms for T1D development at early and late preclinical stages of disease formation in children and adolescents. Material and methods. At the State Institution «V.P. Komisarenko Institute of Endocrinology and Metabolism of NAMS of Ukraine» mentioned the Program «Immunity in the preclinical period of T1D development» was initiated, on the basis of which the Register of marker-positive children with predictable development of type 1 diabetes was created, which includes 612 children aged from 7 to 15 years with burdened heredity, in which the titer of diabetes-associated autobodies (DAA), cytokines, levels of basal and postprandial glycemia and secretion of C-peptide at preclinical and clinical stages of T1D development in children and adolescents based on the performed clinical and immunological study. Results. The new data have been obtained at the State Institution «V.P. Komisarenko Institute of Endocrinology and Metabolism of NAMS of Ukraine», which allowed to substantially supplement the existing ideas about the type 1 diabetes (T1D) pathogenesis. As a result of the performed study, a group of marker-positive children with burdened heredity and a predicted risk of developing the disease was formed. It was found that an increased titer of DAA was observed in 162 (35.45%) of 457 children with burdened heredity with no less than two times determination of DAA presence in them, mainly GADA and IA‑2A, the clinical debut was manifested in 86 (53.08%) of them from 6 months to 16 years (27.4±4.3 months). The formula of combined occurrence and values of simultaneously increased DAA titers to islet autoantigens, namely IA‑2A + GADA, was determined, which is a predictor of both the duration of preclinical stage of T1D development and the debut rate. Impaired cytokine production (increase of the level of proinflammatory cytokines IL‑1α, IL‑6 and TNFα, IL‑8 and IL‑16 while reducing the concentration of IL‑4 in the PB) as key factors of the T1D pathogenesis, which determine the rate of T1D debut, and the aggressiveness of its course were also established. It was found that the early preclinical period of T1D development in DAA+ children was characterized by the presence of dysglycemia in the form of increased glycemia in 2 hour after the glucose tolerance test and a slight decrease in secretion of stimulated C-peptide; in addition, dysglycemia in the form of impaired fasting glycemia was added in DAA+
children in the late preclinical period, and a decrease in both basal and stimulated secretion of the C-peptide was determined, indicating that the potential of pancreatic beta cells was depleted.



1. Тронько МД. Досягнення та перспективи розвитку сучасної ендокринології в Україні (до 25-річчя НАМН України). Ендокринологія. 2019;23(1):5-15. (Tron’ko MD. Achievements and prospects of development of modern endocrinology in Ukraine (to the 25th anniversary of the National Academy of Medical
Sciences of Ukraine). Endokrynolohiya. 2019;23(1):5-15).
2. Зак КП, Тронько НД, Попова ВВ, Бутенко АК. Сахарный диабет. Иммунитет. Цитокины. Київ: Книга-плюс, 2015;488 с. (Zak KP, Tronko ND, Popova VV, Butenko AK. Diabetes. Immunity. Cytokines. Kyiv: Knyha-plyus, 2015;488 p.).
3. Atkinson MA. The pathogenesis and natural history of type 1 diabetes. Cold Spring Harb Perspect Med. 2012;2(11): a007641.
4. Atkinson MA. Thirty years of investigating the autoimmune basis for type 1 diabetes: Why can’t we prevent or reverse this disease. Diabetes. 2005;54(5):1253-63.
5. Atkinson MA, Eisenbarth GS, Michels AW. Type 1 diabetes. Lancet. 2014;383(9911): 69-82.
6. Bender Ch, Schlosser M, Christen U. GAD autoantibody affinity in schoolchildren from the general population. Diabetologia. 2014;57(9):1911-8.
7. He JS, Xie PS, Luo DS. Role of immune dysfunction in pathogenesis of type 1 diabetes mellitus in children. Asian Pacific J. Tropical Medicine. 2014;7(10):823-6.
8. Sherry NA, Tsai EB, Herold KC. Natural history of β-cell function in type 1 diabetes. Diabetes. 2005;54(Suppl 2): S32-9.
9. Sosenko JM, Skyler JS, Palmer JP. A longitudinal study of GAD65 and ICA512 autoantibodies during the progression to type 1 diabetes in Diabetes Prevention Trial–Type 1 (DPT‑1) participants. Diabetes Care. 2011;34(11):2435-7.
10. Bingley PJ. Interactions of age, islet cell antibodies, insulin autoantibodies, and first-phase insulin response in predicting risk of progression to IDDM in ICA+ relatives: the ICARUS data set. Islet Cell Antibody Register Users Study.Diabetes. 1996;45(12): 1720-8.
11. Chmiel R, Giannopoulou EZ, Winkler Ch. Progression from single to multiple islet autoantibodies often occurs soon after seroconversion: implications for early screening. Diabetologia. 2015;58(2):411-3.
12. Gabbay MAL, Sato MN, Duarte AJS, Dib SA. Serum titres of anti-glutamic acid decarboxylase‑65 and anti-IA‑2 autoantibodies are associated with different immunoregulatory milieu in newly diagnosed type 1 diabetes patients. Clin Exp Immunol. 2012;168(1):60-7.
13. Lebastchi J, Herold KC. Immunologic and metabolic biomarkers of β-cell destruction in the diagnosis of type 1 diabetes. Cold Spring Harb Perspect Med. 2012;2(6): a007708.
14. Pietropaolo M, Towns R, Eisenbarth GS. Humoral autoimmunity in type 1 diabetes: prediction, significance, and detection of distinct disease subtypes. Cold Spring Harb Perspect Med. 2012;2(10): a012831.
15. Pihoker C, Gilliam LK, Hampe CS, Lernmark Å. Autoantibodies in diabetes. Diabetes. 2005;54(Suppl 2): S52-61.