diaendoСахарный диабетDiabetes mellitus2072-03512072-0378Endocrinology research centre10.14341/DM12921diaendo-12921Research ArticleОригинальные исследованияOriginal StudiesРоль специфических панкреатических антител в дифференциальной диагностике полной клинико-лабораторной ремиссии сахарного диабета 1 типа и MODY у детейThe role of specific pancreatic antibodies in the differential diagnosis of complete clinical and laboratory remission of type 1 diabetes mellitus and MODY in childrenhttps://orcid.org/0000-0002-8181-5572СечкоЕ. А.SechkoE. A.

Сечко Елена Александровна - кандидат медицинских наук; Researcher ID: S-4114-2016; Scopus Author ID: 55880018700; eLibrary SPIN: 4608-5650.

117036, Москва, ул. Дм. Ульянова, д. 11

Elena A. Sechko - MD, PhD; Researcher ID: S-4114-2016; Scopus Author ID: 55880018700; eLibrary SPIN: 4608-5650.

11 Dm. Ulyanova street, 117036 Moscow

elena.sechko@bk.ruhttps://orcid.org/0000-0003-0123-8857РоманенковаЕ. М.RomanenkovaE. M.

Романенкова Елизавета Михайловна - Researcher ID: AAB-7186-2021; eLibrary SPIN: 6190-0118.

Москва

Elizaveta M. Romanenkova - MD; Researcher ID: AAB-7186-2021; eLibrary SPIN: 6190-0118.

Moscow

romanenkovae@list.ruhttps://orcid.org/0000-0001-7021-1151ЕреминаИ. А.EreminaI. A.

Еремина Ирина Александровна - кандидат медицинских наук; Researcher ID: S-3979-2016; Scopus Author ID: 6701334405.

Москва

Irina A. Eremina - MD, PhD; Researcher ID: S-3979-2016; Scopus Author ID: 6701334405.

Moscow

ieremina58@gmail.comhttps://orcid.org/0000-0002-0316-8314ЗильберманЛ. И.ZilbermanL. I.

Зильберман Любовь Иосифовна - кандидат медицинских наук; eLibrary SPIN 4488-7724.

Москва

Lubov I. Zilberman - MD, PhD; eLibrary SPIN 4488-7724.

Moscow

zilbermanl@yandex.ruНиканкинаЛ. В.NikankinaL. V.

Никанкина Лариса Вячеславовна - кандидат медицинских наук; eLibrary SPIN: 4679-9356.

Москва

Larisa V. Nikankina - MD, PhD; eLibrary SPIN: 4679-9356.

Moscow

lnikankina@mail.ruhttps://orcid.org/0000-0001-6953-6928ЗураеваЗ. Т.ZuraevaZ. T.

Зураева Замира Тотразовна - кандидат медицинских наук; eLibrary SPIN: 6002-0455.

Москва

Zamira T. Zuraeva - MD, PhD; eLibrary SPIN: 6002-0455.

Moscow

zuraeva_zamira@mail.ruhttps://orcid.org/0000-0001-9621-5732БезлепкинаО. Б.BezlepkinaO. B.

Безлепкина Ольга Борисовна - доктор медицинских наук; Researcher ID: B-6627-2017; Scopus Author ID: 6507632848; eLibrary SPIN: 3884-0945.

Москва

Olga B. Bezlepkina - MD, PhD; Researcher ID: B-6627-2017; Scopus Author ID: 6507632848; eLibrary SPIN: 3884-0945.

Moscow

olgabezlepkina@mail.ruhttps://orcid.org/0000-0002-5507-4627ПетерковаВ. А.PeterkovaV. A.

Петеркова Валентина Александровна - доктор медицинских наук, профессор, академик РАН; e-library SPIN: 4009-2463.

Москва

Valentina A. Peterkova - MD, PhD, Professor, academician of Russian Academy of Medical Sciences; e-library SPIN: 4009-2463.

Moscow

peterkovava@hotmail.comhttps://orcid.org/0000-0002-4316-8546ЛаптевД. Н.LaptevD. N.

Лаптев Дмитрий Никитич - доктор медицинских наук; Researcher ID: O-1826-2013; Scopus Author ID: 24341083800; e-library SPIN: 2419-4019.

Москва

Dmitry N. Laptev - MD, PhD; Researcher ID: O-1826-2013; Scopus Author ID: 24341083800; e-library SPIN: 2419-4019.

Moscow

laptevdn@ya.ruНациональный медицинский исследовательский центр эндокринологииРоссияEndocrinology Research CentreRussian Federation202230112022255449457Copyright © Сечко Е.А., Романенкова Е.М., Еремина И.А., Зильберман Л.И., Никанкина Л.В., Зураева З.Т., Безлепкина О.Б., Петеркова В.А., Лаптев Д.Н., 20222022Сечко Е.А., Романенкова Е.М., Еремина И.А., Зильберман Л.И., Никанкина Л.В., Зураева З.Т., Безлепкина О.Б., Петеркова В.А., Лаптев Д.Н.Sechko E.A., Romanenkova E.M., Eremina I.A., Zilberman L.I., Nikankina L.V., Zuraeva Z.T., Bezlepkina O.B., Peterkova V.A., Laptev D.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.dia-endojournals.ru/jour/article/view/12921ОБОСНОВАНИЕ

ОБОСНОВАНИЕ. Сахарный диабет 1 типа (СД1) характеризуется аутоиммунным разрушением β-клеток, обусловленным влиянием факторов окружающей среды и генетической предрасположенностью. После начала инсулинотерапии у 80% детей с СД1 отмечаются снижение дозы инсулина и развитие клинико-лабораторной ремиссии СД1, или «медового месяца». При длительном отсутствии потребности в инсулине в случаях ранней доклинической диагностики СД1 и при полной клинико-лабораторной ремиссии СД1 более 6 мес возникает вопрос о необходимости проведения дифференциальной диагностики между аутоиммунным СД и неиммунными формами СД.

ЦЕЛЬ

ЦЕЛЬ. Изучить клинические, иммунологические, генетические характеристики ремиссии СД1 и диабета взрослого типа у молодых лиц (MODY) у детей, определить дифференциально-диагностические критерии СД1 и MODY у детей.

МАТЕРИАЛЫ И МЕТОДЫ

МАТЕРИАЛЫ И МЕТОДЫ. Одноцентровое одномоментное двухвыборочное неконтролируемое сравнительное исследование, включающее данные 150 детей, госпитализированных в ФГБУ «НМИЦ эндокринологии» в 2016–2021 гг. Изучены 2 популяции пациентов: 1-я популяция — пациенты с полной клинико-лабораторной ремиссией СД1 (n=36), 2-я популяция — пациенты с MODY, подтвержденным в ходе молекулярно-генетического исследования (n=114).

РЕЗУЛЬТАТЫ

РЕЗУЛЬТАТЫ. Медиана возраста манифестации СД значимо выше у пациентов с СД1 — 11,25 года [8,33; 13,78] против MODY — 7,5 года [4,6; 12,2] (p=0,004). У пациентов с ремиссией СД1 уровень гликированного гемоглобина составил 6,0% [5,6; 6,4], при MODY — 6,5% [6,2; 6,7] (p<0,001). Для пациентов с MODY наиболее характерно нарушение гликемии натощак — 6,27 ммоль/л [5,38; 6,72], тогда как для ремиссии СД1 характерна нормогликемия — 5,12 ммоль/л [4,17; 5,87]. При проведении перорального глюкозотолерантного теста уровни гликемии на 120-й минуте в 2 группах значимо не отличались (p=0,08). Отягощенный наследственный анамнез у пациентов с MODY отмечался чаще (93% против 66,7%). Положительный титр аутоантител (АТ) чаще определялся у пациентов с ремиссией СД1 — 77,8%, у пациентов с MODY — 11,4%. У пациентов с MODY выявлялось повышение титра не более 1 вида АТ.

ЗАКЛЮЧЕНИЕ

ЗАКЛЮЧЕНИЕ. Наибольшую значимость для проведения дифференциальной диагностики СД1 и MODY при длительном инсулиннезависимом периоде (более 6 мес) у детей с СД показали АТ ZnT8 и IA2. При отсутствии АТ рекомендовано проведение молекулярной диагностики. При выявлении только одного типа АТ решение о необходимости молекулярно-генетического анализа должно проводиться на основании комплексного анализа фенотипических характеристик пациента, включая данные наследственного анамнеза, особенности манифестации, показателей углеводного обмена.

BACKGROUND

BACKGROUND: T1D is characterized by autoimmune destruction of pancreatic β-cells, which develops due to genetic and environmental risk factors. Shortly after initiating the treatment with insulin, 80% of children with T1D may require smaller doses of insulin and develop clinical and laboratory remission of the disease so called «honeymoon». The issue of whether there is a need of differential diagnosis between autoimmune DM and non-immune forms of DM raises in cases of preclinical diagnosis of T1D and laboratory remission for more than 6 months.

AIM

AIM: To study the clinical, immunological, genetic characteristics of T1D remission phase and MODY in children, to determine the diagnostic criteria for T1D and MODY in children.

MATERIALS AND METHODS

MATERIALS AND METHODS: A single-centre, cross sectional noncontrolled comparative study of two independent cohorts. Data of 150 children examined in the Endocrinology Research Center (January 2016–June 2021). First cohort included patients with complete clinical and laboratory remission of T1D (n=36), second cohort included patients with MODY, confirmed by genetic study (n=114).

RESULTS

RESULTS: The median age of diabetes manifestation was significantly higher in patients with T1D — 11.25 years [8.33; 13.78] than in patients with MODY — 7.5 years [4.6; 12.2] (p=0.004). In patients with T1D remission the level of glycated hemoglobin was 6.0% [5.6; 6.4], in group with MODY — 6.5% [6.2; 6.7] (p<0.001). Patients with monogenic diabetes had impaired fasting glucose — 6.27 mmol/l [5.38; 6.72], while patients with remission phase had normoglycemia — 5.12 mmol/l [4.17; 5.87]. The oral glucose tolerance test was perform to all patients, two-hour glucose level did not significantly differ in two groups (p=0.08). A strong family history of diabetes in patients with MODY registered more often (93% vs. 66.7%). A positive autoantibody titer detected more often in patients with remission of T1D (77.8%) than in patients with MODY (11.4%). In addition, no more than 1 type of autoantibodies was detected in patients with MODY.

CONCLUSION

CONCLUSION: Antibodies ZnT8 and IA2 showed the greatest significance for the differential diagnosis of T1D and MODY in cases with long absents of insulin requirement in children with diabetes mellitus. Genetic test is recommended in seronegative cases. If only one type of AT is detected, specialist should decide on the need to do diagnostic genetic test based on a comprehensive analysis of the patient’s clinic characteristics, including family history, manifestation and blood glucose levels.

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The authors declare that there are no conflicts of interest present.