diaendoСахарный диабетDiabetes mellitus2072-03512072-0378Endocrinology research centre10.14341/DM13200diaendo-13200Research ArticleОригинальные исследованияOriginal StudiesКлинико-лабораторные и генетические особенности семейных форм сахарного диабета 1 типаClinical, bio­chemical and genetic characteristics of familial forms of type 1 diabeteshttps://orcid.org/0000-0002-5463-0425ЗуфароваЮ. М.ZufarovaI. M.

Зуфарова Юлдуз Муроджоновна; Researcher ID: AGE-4004-2022.

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

Iulduz M. Zufarova - MD; Researcher ID: AGE-4004-2022.

11 Dm. Ulyanova street, 117036 Moscow

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

Лаптев Дмитрий Никитич, д.м.н..; Researcher ID: O-1826-2013; Scopus Author ID: 24341083800

Москва

Dmitry N. Laptev - MD, PhD

Moscow

laptevdn@ya.ruhttps://orcid.org/0000-0002-7045-8215МинниахметовИ. Р.MinniahmetovI. R.

Минниахметов Илдар Рамилевич - к.б.н.

Москва

Ildar R. Minniakhmetov - PhD in Biology.

Moscow

minniakhmetov@gmail.comhttps://orcid.org/0000-0002-8643-850XХусаиноваР. И.KhusainovaR. I.

Хусаинова Рита Игоревна - д.б.н. ; Researcher ID: E-6061-2014; Scopus Author ID: 6602798130.

Москва

Rita I. Khusainova -PhD in Biology ; Researcher ID: E-6061-2014; Scopus Author ID: 6602798130.

Moscow

https://orcid.org/0000-0003-1172-3557ПоповС. В.PopovS. V.

Попов Сергей Владимирович - к.б.н.

Москва

Sergey V. Popov, PhD in Biology.

Moscow

swpopov73@gmail.comhttps://orcid.org/0000-0001-7821-3979ТитовичЕ. В.TitovichE. V.

Титович Елена Витальевна - к.м.н.; Researcher ID: AAO-2567-2020; Scopus Author ID: 6507024916.

Москва

Elena V. Titovich - MD, PhD; Researcher ID: AAO-2567-2020; Scopus Author ID: 6507024916.

Moscow

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

Еремина Ирина Александровна - к.м.н. ; 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/0000-0002-5507-4627ПетерковаВ. А.PeterkovaV. A.

Петеркова Валентина Александровна - д.м.н., профессор, академик РАН.

Москва

Valentina A. Peterkova - PhD, Professor, Academician of the RAS.

Moscow

peterkovava@hotmail.comГНЦ РФ ФГБУ «Национальный медицинский исследовательский центр эндокринологии»РоссияEndocrinology Research CentreRussian Federation202417012025276520527Copyright © Зуфарова Ю.М., Лаптев Д.Н., Минниахметов И.Р., Хусаинова Р.И., Попов С.В., Титович Е.В., Еремина И.А., Петеркова В.А., 20252025Зуфарова Ю.М., Лаптев Д.Н., Минниахметов И.Р., Хусаинова Р.И., Попов С.В., Титович Е.В., Еремина И.А., Петеркова В.А.Zufarova I.M., Laptev D.N., Minniahmetov I.R., Khusainova R.I., Popov S.V., Titovich E.V., Eremina I.A., Peterkova V.A.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/13200ОБОСНОВАНИЕ

ОБОСНОВАНИЕ. Семейные формы сахарного диабета 1 типа (СД1) представляют особый интерес в связи с высокой концентрацией заболевания, что может быть обусловлено особыми генетическими и средовыми факторами. Их изучение может позволить лучше понять и выявить новые иммунологические и генетические особенности СД1.

ЦЕЛЬ

ЦЕЛЬ. Изучить клинико-лабораторные и генетические особенности семейных форм СД1.

МАТЕРИАЛЫ И МЕТОДЫ

МАТЕРИАЛЫ И МЕТОДЫ. Одноцентровое одномоментное исследование, включающее 267 пациентов с семейной формой СД1, и 681 пациента со спорадической формой СД1, госпитализированных в ФГБУ «НМИЦ эндокринологии» МЗ РФ в 2016–2023 гг., у которых проведена оценка клинических, лабораторных и генетических параметров.

РЕЗУЛЬТАТЫ

РЕЗУЛЬТАТЫ. Медиана возраста манифестации была значимо ниже у детей с семейной формой СД1 (5,2 [3,0; 8,0] и 6,4 [3,6; 9,2] соответственно, p<0,001). Острая манифестация заболевания в состоянии кетоза или диабетического кетоацидоза (ДКА) отмечалась чаще в группе со спорадической формой СД1 (90,3% vs 74%, p<0,001). Частота ДКА в дебюте заболевания в группе сибсов, заболевших в семье первыми, составила 50,5%, в группе сибсов, заболевших вторыми и третьими, — 19,5%, в то время как у детей из семей, где один или оба родителя имеют СД1, — 21% (p<0,001). У детей с семейной формой СД1 чаще выявлялись антитела IAA и GAD (p<0,013 и p<0,003 соответственно). Значимых различий в показателях метаболической компенсации СД1 в исследуемых группах не отмечалось. Предрасполагающие HLA-гаплотипы DRB1*04-DQA1*03:03-DQB1*03:02 и DRB1*07-DQA1*02:01-DQB1*02:02 чаще встречались при семейной форме СД1 (p<0,001 и p<0,001), в то время как протекторный гаплотип DRB1*08-DQA1*04:01-DQB1*04:02 — при спорадической форме.

ЗАКЛЮЧЕНИЕ

ЗАКЛЮЧЕНИЕ. Семейные формы СД1 характеризуются более ранним возрастом, меньшим, но все еще значимым риском ДКА при манифестации заболевания, а также особенностями иммунологического профиля и распределения предрасполагающих и защитных HLA-гаплотипов. Полученные данные будут способствовать улучшению прогнозирования рисков и дальнейшим исследованиям в области изучения патогенеза СД1.

BACKGROUND

BACKGROUND: Familial clustering of type 1 diabetes (T1D) highlights the importance of genetic and environmental factors in the pathophysiology of diabetes mellitus (DM). It could be the key to understanding of new immunological and genetic characteristics of T1D.

AIM

AIM: To study the clinical, biochemical, immunological and genetic characteristics of children with familial forms of T1D.

MATERIALS AND METHODS

MATERIALS AND METHODS: A single-center cross-sectional study included 267 patients with familial T1D and 681 patients with sporadic T1D. Clinical and metabolic characteristics, beta cell autoantibodies and HLA class II genetics from patients with T1D hospitalized to Endocrinology Research Centre Moscow between 2016 and 2023 were analyzed.

RESULTS

RESULTS: The median age of onset of DM was significantly lower in children with familial T1D (5,2 [3,0; 8,0] vs 6,4 [3,6; 9,2], p<0,001). Children with sporadic T1D had diabetic ketosis or diabetic ketoacidosis (DKA) at presentation more frequently (90,3% vs 74%, p<0,001). Among the sib-pair groups 50,5% of first-affected siblings and 19,5% of second- and third-affected siblings had DKA at presentation, while in children from parent-offspring subgroup DKA episodes were observed in 21% of patients (p<0,001). IAA and GAD antibodies were more frequent in familial cases (p<0,013, p<0,003). In our groups, no significant differences in metabolic compensation of the T1D were found. HLA haplotypes associated with an increased disease risk DRB1*04-DQA1*03:03-DQB1*03:02 and DRB1*07-DQA1*02:01-DQB1*02:02 were more common in children with familial T1D (p<0.001 and p<0.001), while the protective haplotype DRB1*08-DQA1*04:01-DQB1*04:02 was more frequent in sporadic forms.

CONCLUSION

CONCLUSION: Due to our study familial forms of T1D are characterized by an earlier age of onset, a smaller risk of DKA at presentation, as well as features of the immunological profile and predisposing and protective HLA haplotypes presentation. We believe more studies are required in the future to look for risk factors and pathogenesis unserstanding.

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