diaendoСахарный диабетDiabetes mellitus2072-03512072-0378Endocrinology research centre10.14341/DM13011diaendo-13011Research ArticleКлинический случайCase reportСахарный диабет, ассоциированный с синдромом инсулинорезистентности типа АDiabetes mellitus associated with type A insulin resistancehttps://orcid.org/0000-0002-8181-5572СечкоЕ. А.SechkoE. A.

Сечко Елена Александровна - кандидат медицинских наук.

117292, Москва, ул. Дм. Ульянова, д. 11

Elena A. Sechko - MD, PhD.

11 Dm. Ulyanova street, Moscow 117292

elena.sechko@bk.ruhttps://orcid.org/0000-0003-4950-3920КураеваТ. Л.KuraevaT. L.

Кураева Тамара Леонидовна - доктор медицинских наук, профессор.

Москва

Tamara L. Kuraeva - MD, PhD, Professor.

Moscow

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

Петеркова Валентина Александровна - доктор медицинских наук, профессор, академик РАН.

Москва

Valentina A. Peterkova - MD, PhD, Professor, academician of Russian Academy of Medical Sciences

Moscow

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

Лаптев Дмитрий Никитич, доктор медицинских наук.

Москва

Dmitry N. Laptev - MD, PhD.

Moscow

laptevdn@ya.ruГНЦ РФ ФГБУ «Национальный медицинский исследовательский центр эндокринологии»РоссияEndocrinology Research CentreRussian Federation202314072023263284290Copyright © Сечко Е.А., Кураева Т.Л., Петеркова В.А., Лаптев Д.Н., 20232023Сечко Е.А., Кураева Т.Л., Петеркова В.А., Лаптев Д.Н.Sechko E.A., Kuraeva T.L., 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/13011

Синдром инсулинорезистентности типа А — моногенное заболевание, в основе которого лежит дефект действия инсулина, наблюдается у лиц женского пола с acantosis nigricans (AN), гиперандрогенией, гиперинсулинемией, инсулинорезистентностью (ИР) без ожирения. Представлен семейный случай сахарного диабета (СД) с ИР у двух сестер с ожирением и отягощенной наследственностью по СД в трех поколениях. Через 5–6 мес после перенесенной инфекции COVID-19 была зафиксирована гипергликемия в 13 лет у старшей сестры и в 11 — у младшей сестры. У матери, 40 лет, СД 2 типа (СД2) диагностирован одновременно с детьми. У бабушки по материнской линии СД2 с 58 лет. Через 6 мес после диагностики гипергликемии проведено обследование. У старшей сестры отмечались ожирение, AN, стрии. Уровень гликированного гемоглобина (HbA1c) 6,2%, нарушение толерантности к глюкозе (НТГ), гиперинсулинемия и ИР, гиперандрогения. Диагностированы неалкогольная жировая болезнь печени (НАЖБП), артериальная гипертензия. У младшей сестры — ожирение, стрии. HbA1c — 6,0%. Диагностированы нарушение гликемии натощак, НТГ, гиперинсулинемия, ИР, НАЖБП. Аутоантитела (ААт) к ZnT8A, IA2, GAD отсутствовали у обеих сестер. При молекулярно-генетическом исследовании выявлена гетерозиготная мутация в гене INSR p.V167M у обеих сестер, матери и бабушки. Особенностью данного клинического случая является диагностика синдрома ИР типа А в семье с фенотипом СД2, что демонстрирует необходимость проведения молекулярно-генетического исследования детям с нарушениями углеводного обмена и ожирением при отсутствии ААт. Одновременная диагностика СД у трех членов одной семьи после перенесенной инфекции COVID-19, ранее не имевших нарушений углеводного обмена, позволяет предполагать, что SARS-CoV-2 может явиться триггером развития нарушений углеводного обмена при ИР типа А.

Insulin resistance type A is a monogenic disorder with insulin action defect, observed in females with acanthosis nigricans (AN), hyperandrogenism, hyperinsulinemia, insulin resistance (IR) without obesity. We present a family case of diabetes mellitus (DM) with IR in two sisters with obesity and positive family history of DM in three generations. Hyperglycemia was identified at the age of 13 in the older sister and at 11 in the younger sister after COVID-19. Type 2 diabetes (DM2) was diagnosed in mother in the same time with children. Maternal grandmother was diagnosed with DM2 in 58 years old. Patients were examined in 6 months after diagnosis hyperglycemia in Endocrinology Research Centre. The older sister had obesity, AN, and striae distensae. Glycosylated hemoglobin (HbA1c) 6.2%. Impaired glucose tolerance (IGT), hyperinsulinemia and IR, hyperandrogenism, non-alcoholic fatty liver disease (NAFLD), arterial hypertension were diagnosed. The younger sister had obesity, striae distensae. HbA1c — 6.0%. Impaired fasting glucose (IFG), IGT, hyperinsulinemia, IR, NAFLD were diagnosed. Antibodies (AAb) to ZnT8A, IA2, GAD absented in both sisters. A genetic test was provided, a heterozygous mutation in the INSR gene p.V167M was identified in both sisters, mother and grandmother. IR type A was identified in a family with the phenotype of DM2 in this case. This case demonstrated that children with carbohydrate metabolism disorders and obesity without Islet cell autoantibodies have to reffered for a genetic testing. Disordered carbohydrate metabolism was diagnosed in the same time after a COVID-19 in three family members who did not previously have disordered carbohydrate metabolism. We suppose that SARS-CoV-2 can be a trigger for the development of carbohydrate metabolism disorders in IR type A.

сахарный диабет у детейинсулинорезистентностьинсулинорезистеность типа Амоногенный сахарный диабетрецептор инсулинаген INSRгиперандрогенияdiabetes mellitus in childreninsulin resistanceinsulin resistance type Amonogenic diabetes mellitusinsulin receptorgene INSRhyperandrogenismИсследование выполнено в рамках государственного задания, номер государственного учета 123021000040-9ReferencesLevy-Marchal C, Arslanian S, Cutfield W, et al. Insulin resistance in children: Consensus, perspective, and future directions. J Clin Endocrinol Metab. 2010;95(12):5189-5198. doi: https://doi.org/10.1210/jc.2010-1047Levy-Marchal C, Arslanian S, Cutfield W, et al. Insulin resistance in children: Consensus, perspective, and future directions. J Clin Endocrinol Metab. 2010;95(12):5189-5198. doi: https://doi.org/10.1210/jc.2010-1047Tagi VM, Giannini C, Chiarelli F. Insulin resistance in children. Front Endocrinol (Lausanne). 2019;10:S23-S27. doi: https://doi.org/10.3389/fendo.2019.00342Tagi VM, Giannini C, Chiarelli F. Insulin resistance in children. Front Endocrinol (Lausanne). 2019;10:S23-S27. doi: https://doi.org/10.3389/fendo.2019.00342Ten S, Maclaren N. Insulin resistance syndrome in children. J Clin Endocrinol Metab. 2004;89(6):2526-2539. doi: https://doi.org/10.1210/jc.2004-0276Ten S, Maclaren N. Insulin resistance syndrome in children. J Clin Endocrinol Metab. 2004;89(6):2526-2539. doi: https://doi.org/10.1210/jc.2004-0276Kleinberger JW, Copeland KC, Gandica RG, et al. Monogenic diabetes in overweight and obese youth diagnosed with type 2 diabetes: the TODAY clinical trial. Genet Med. 2018;20(6):583-590. doi: https://doi.org/10.1038/gim.2017.150Kleinberger JW, Copeland KC, Gandica RG, et al. Monogenic diabetes in overweight and obese youth diagnosed with type 2 diabetes: the TODAY clinical trial. Genet Med. 2018;20(6):583-590. doi: https://doi.org/10.1038/gim.2017.150Сечко Е.А., Кураева Т.Л., Зильберман Л.И., и др.. Неиммунный сахарный диабет у детей, обусловленный гетерозиготными мутациями в гене глюкокиназы (GCK-MODY): анализ данных 144 пациентов // Сахарный диабет. — 2022. — Т. 25. — №5. — С. 145-154. doi: https://doi.org/10.14341/DM12819Sechko EA, Kuraeva TL, Zilberman LI, et al. Non-immune diabetes mellitus in children due to heterozygous mutations in the glucokinase gene (GCK-MODY): data of 144 patients. Diabetes mellitus. 2022;25(2):145-154. (In Russ.)]. doi: https://doi.org/10.14341/DM12819Kirkwood A, Stuart G, Harding L. Donohue syndrome: A review of literature, case series, and anesthetic considerations. Pediatr Anesth. 2018;28(1):23-27. doi: https://doi.org/10.1111/pan.13273Kirkwood A, Stuart G, Harding L. Donohue syndrome: A review of literature, case series, and anesthetic considerations. Pediatr Anesth. 2018;28(1):23-27. doi: https://doi.org/10.1111/pan.13273Longo N, Singh R, Griffin LD, et al. Impaired growth in RabsonMendenhall syndrome: lack of effect of growth hormone and insulinlike growth factor-I. J Clin Endocrinol Metab. 1994;79(3):799-805. doi: https://doi.org/10.1210/jcem.79.3.8077364Longo N, Singh R, Griffin LD, et al. Impaired growth in RabsonMendenhall syndrome: lack of effect of growth hormone and insulinlike growth factor-I. J Clin Endocrinol Metab. 1994;79(3):799-805. doi: https://doi.org/10.1210/jcem.79.3.8077364Angelidi AM, Filippaios A, Mantzoros CS. Severe insulin resistance syndromes. J Clin Invest. 2021;131(4):e142245. doi: https://doi.org/10.1172/JCI142245Angelidi AM, Filippaios A, Mantzoros CS. Severe insulin resistance syndromes. J Clin Invest. 2021;131(4):e142245. doi: https://doi.org/10.1172/JCI142245Saito-Hakoda A, Nishii A, Uchida T, et al. A follow-up during puberty in a Japanese girl with type A insulin resistance due to a novel mutation in INSR. Clin Pediatr Endocrinol. 2018;27(1):53-57. doi: https://doi.org/10.1297/cpe.27.53Saito-Hakoda A, Nishii A, Uchida T, et al. A follow-up during puberty in a Japanese girl with type A insulin resistance due to a novel mutation in INSR. Clin Pediatr Endocrinol. 2018;27(1):53-57. doi: https://doi.org/10.1297/cpe.27.53Seino S, Bell GI. Alternative splicing of human insulin receptor messenger RNA. Biochem Biophys Res Commun. 1989;159(1):312-316. doi: https://doi.org/10.1016/0006-291X(89)92439-XSeino S, Bell GI. Alternative splicing of human insulin receptor messenger RNA. Biochem Biophys Res Commun. 1989;159(1):312-316. doi: https://doi.org/10.1016/0006-291X(89)92439-XEpstein FH, Moller DE, Flier JS. Insulin resistance — mechanisms, syndromes, and implications. N Engl J Med. 1991;325(13):938-948. doi: https://doi.org/10.1056/NEJM199109263251307Epstein FH, Moller DE, Flier JS. Insulin resistance — mechanisms, syndromes, and implications. N Engl J Med. 1991;325(13):938-948. doi: https://doi.org/10.1056/NEJM199109263251307Ullrich A, Bell JR, Chen EY, et al. Human insulin receptor and its relationship to the tyrosine kinase family of oncogenes. Nature. 1985;313(6005):756-761. doi: https://doi.org/10.1038/313756a0Ullrich A, Bell JR, Chen EY, et al. Human insulin receptor and its relationship to the tyrosine kinase family of oncogenes. Nature. 1985;313(6005):756-761. doi: https://doi.org/10.1038/313756a0Ebina Y, Ellis L, Jarnagin K, et al. The human insulin receptor cDNA: The structural basis for hormone-activated transmembrane signalling. Cell. 1985;40(4):747-758. doi: https://doi.org/10.1016/0092-8674(85)90334-4Ebina Y, Ellis L, Jarnagin K, et al. The human insulin receptor cDNA: The structural basis for hormone-activated transmembrane signalling. Cell. 1985;40(4):747-758. doi: https://doi.org/10.1016/0092-8674(85)90334-4Ardon O, Procter M, Tvrdik T, et al. Sequencing analysis of insulin receptor defects and detection of two novel mutations in INSR gene. Mol Genet Metab Reports. 2014;(1):71-84. doi: https://doi.org/10.1016/j.ymgmr.2013.12.006Ardon O, Procter M, Tvrdik T, et al. Sequencing analysis of insulin receptor defects and detection of two novel mutations in INSR gene. Mol Genet Metab Reports. 2014;(1):71-84. doi: https://doi.org/10.1016/j.ymgmr.2013.12.006Kahn CR, Flier JS, Bar RS, et al. The syndromes of insulin resistance and acanthosis nigricans: insulin-receptor disorders in man. N Engl J Med. 1976;294(14):739-745. doi: https://doi.org/10.1056/NEJM197604012941401Kahn CR, Flier JS, Bar RS, et al. The syndromes of insulin resistance and acanthosis nigricans: insulin-receptor disorders in man. N Engl J Med. 1976;294(14):739-745. doi: https://doi.org/10.1056/NEJM197604012941401Riqué S, Nogués C, Ibàñez L, et al. Identification of three novel mutations in the insulin receptor gene in type A insulin resistant patients. Clin Genet. 2000;57(1):67-69. doi: https://doi.org/10.1034/j.1399-0004.2000.570110.xRiqué S, Nogués C, Ibàñez L, et al. Identification of three novel mutations in the insulin receptor gene in type A insulin resistant patients. Clin Genet. 2000;57(1):67-69. doi: https://doi.org/10.1034/j.1399-0004.2000.570110.xПетеркова В.А., Кураева Т.Л., Зильберман Л.И., и др. Генетические дефекты действия инсулина. В кн.: Сахарный диабет: многообразие клинических форм / Под ред. Дедова И.И., Шестаковой М.В. — М.: Изд-во МИА; 2016. — С. 114-122.Peterkova VA, Kuraeva TL, Zilberman LI, et al. Geneticheskie defekty deystviya insulin. In: Sakharnyi diabet: mnogoobrazie klinicheskih form. Ed by Dedov II, Shestakova MV. Moscow: MIA; 2016. P. 114-122. (In Russ.).Domínguez-García Á, Martínez R, Urrutia I, et al. Identification of a novel insulin receptor gene heterozygous mutation in a patient with type A insulin resistance syndrome. J Pediatr Endocrinol Metab. 2014;27(5-6):67-69. doi: https://doi.org/10.1515/jpem-2013-0284Domínguez-García Á, Martínez R, Urrutia I, et al. Identification of a novel insulin receptor gene heterozygous mutation in a patient with type A insulin resistance syndrome. J Pediatr Endocrinol Metab. 2014;27(5-6):67-69. doi: https://doi.org/10.1515/jpem-2013-0284Musso C, Cochran E, Moran SA, et al. Clinical course of genetic diseases of the insulin receptor (Type A and Rabson-Mendenhall Syndromes): A 30-year prospective. Medicine (Baltimore). 2004;83(4):209-222. doi: https://doi.org/10.1097/01.md.0000133625.73570.54Musso C, Cochran E, Moran SA, et al. Clinical course of genetic diseases of the insulin receptor (Type A and Rabson-Mendenhall Syndromes): A 30-year prospective. Medicine (Baltimore). 2004;83(4):209-222. doi: https://doi.org/10.1097/01.md.0000133625.73570.54Калмыкова З.А., Кононенко И.В., Скляник И.А., и др. Гипергликемия и возможные механизмы повреждения β-клеток у пациентов с COVID-19 // Сахарный диабет. — 2020. — Т. 23. — №3. — С. 229-234. doi: https://doi.org/10.14341/DM12485Kalmykova ZA, Kononenko IV, Sklyanik IA, et al. Hyperglycemia and possible mechanisms of β-cell damage in patients with COVID-19. Diabetes mellitus. 2020;23(3):229-234. (In Russ.). doi: https://doi.org/10.14341/DM12485Российская ассоциация эндокринологов. Клинические рекомендации. Сахарный диабет 2 типа у детей. — M.: МЗ РФ; 2020.Rossijskaja associacija jendokrinologov. Klinicheskie rekomendacii. Saharnyj diabet 2 tipa u detej. Moscow: MZ RF; 2020. (In Russ.).Lehto M, Tuomi T, Mahtani MM, et al. Characterization of the MODY3 phenotype. Early-onset diabetes caused by an insulin secretion defect. J Clin Invest. 1997;99(4):582-591. doi: https://doi.org/10.1172/JCI119199Lehto M, Tuomi T, Mahtani MM, et al. Characterization of the MODY3 phenotype. Early-onset diabetes caused by an insulin secretion defect. J Clin Invest. 1997;99(4):582-591. doi: https://doi.org/10.1172/JCI119199Wilkin TJ. The accelerator hypothesis: weight gain as the missing link between Type I and Type II diabetes. Diabetologia. 2001;44(7):914-922. doi: https://doi.org/10.1007/s001250100548Wilkin TJ. The accelerator hypothesis: weight gain as the missing link between Type I and Type II diabetes. Diabetologia. 2001;44(7):914-922. doi: https://doi.org/10.1007/s001250100548Phiske M. An approach to acanthosis nigricans. Indian Dermatol Online J. 2014;5(3):239. doi: https://doi.org/10.4103/2229-5178.137765Phiske M. An approach to acanthosis nigricans. Indian Dermatol Online J. 2014;5(3):239. doi: https://doi.org/10.4103/2229-5178.137765Diamanti-Kandarakis E, Dunaif A. Insulin Resistance and the Polycystic Ovary Syndrome Revisited: An update on mechanisms and implications. Endocr Rev. 2012;33(6):981-1030. doi: https://doi.org/10.1210/er.2011-1034Diamanti-Kandarakis E, Dunaif A. Insulin Resistance and the Polycystic Ovary Syndrome Revisited: An update on mechanisms and implications. Endocr Rev. 2012;33(6):981-1030. doi: https://doi.org/10.1210/er.2011-1034Wei C, Burren CP. Diagnostic and management challenges from childhood, puberty through to transition in severe insulin resistance due to insulin receptor mutations: WEI AND BURREN. Pediatr Diabetes. 2017;18(8):835-838. doi: https://doi.org/10.1111/pedi.12486Wei C, Burren CP. Diagnostic and management challenges from childhood, puberty through to transition in severe insulin resistance due to insulin receptor mutations: WEI AND BURREN. Pediatr Diabetes. 2017;18(8):835-838. doi: https://doi.org/10.1111/pedi.12486

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