diaendoСахарный диабетDiabetes mellitus2072-03512072-0378Endocrinology research centre10.14341/DM2015220-31diaendo-6985Research ArticleВопросы патогенезаPathogenesisПосттрансплантационный сахарный диабет. Обзор литературыPost-transplantation diabetes mellitus: an overviewСкляникИгорь АлександровичSklyanikIgor Alexandrovich

клинический ординатор

MD, Resident o the Endocrinology Research Centre

sklyanik.igor@gmail.comШамхаловаМинара ШамхаловнаShamkhalovaMinara Shamkhalovna

д.м.н., зав. отделением диабетической нефропатии и  гемодиализа

MD, PhD, Head of Department of Diabetic Nephropathy and Haemodialysis

shamkhalova@mail.ruШестаковаМарина ВладимировнаShestakovaMarina Vladimirovna

MD, PhD, Corresponding member or Russian Academy of Sciences, Director of Diabetes Institute in Endocrinology Research Centre, Head of Diabetology and Endocrinology Department of Pediatric Faculty in Sechenov First Moscow State Medical University

nefro@endocrincentr.ruФГБУ Эндокринологический Научный Центр, МоскваРоссияEndocrinology Research Centre, MoscowRussian FederationФГБУ Эндокринологический научный центр, МоскваРоссияEndocrinology Research Centre, MoscowRussian FederationФГБУ Эндокринологический научный центр, Москва; ГБОУ ВПО Первый МГМУ им. И.М. Сеченова, МоскваРоссияEndocrinology Research Centre, Moscow; Sechenov First Moscow State Medical University, MoscowRussian Federation2015160420151822031Copyright © Скляник И.А., Шамхалова М.Ш., Шестакова М.В., 20152015Скляник И.А., Шамхалова М.Ш., Шестакова М.В.Sklyanik I.A., Shamkhalova M.S., Shestakova M.V.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.dia-endojournals.ru/jour/article/view/6985

Обзор представляет анализ клинических и экспериментальных исследований, посвященных проблеме посттрансплантационного сахарного диабета (ПТСД) ? специфического осложнения после трансплантации солидных органов.Поиск литературных источников проведен по ключевым словам ?посттрансплантационный диабет?, впервые выявленный сахарный диабет?, ?трансплантация?, ?иммуносупрессия?, ?posttransplantation diabetes mellitus?, ?new onset diabetes after transplantation?, ?transplantation?, ?immunosuppression? в реферативных базах данных eLibrary, PubMed, Scopus: 523 результата, в том числе 4 ? в отечественной литературе (1 оригинальное исследование). В анализ вошли оригинальные исследования, обзоры и мета-анализы, а также монографии, опубликованные на русском и английском языке не ранее 2005 г. В обзоре аккумулировано более 60 актуальных на сегодняшний день оригинальных исследований и обзорных статей.Рассмотрены диагностические критерии, факторы риска возникновения заболевания, возможные пути патогенеза. Анализируются механизмы диабетогенного эффекта современных иммуносупрессивных препаратов. Обсуждаются принципы пре- и посттрансплантационного скрининга заболевания, оптимального ведения пациентов. Оцениваются существующие на сегодняшний день спорные вопросы, касающиеся различных аспектов ПТСД.

This review presents an analysis of clinical and experimental studies related to post-transplantation diabetes mellitus (PTDM) ? a specific complication after solid organ transplantation. A search of the databases eLibrary, PubMed and Scopus using the keywords ?posttransplantation diabetes mellitus?, ?new onset diabetes after transplantation?, ?transplantation? and ?immunosuppression? yielded in 523 results, including four from Russian literature (one original research manuscript). The analysis included original research, reviews, meta-analyses and monographs published not before 2005 in Russian and English. A total of 60 relevant original researches and reviews were included in this review. Diagnostic criteria, disease risk factors and potential pathogenic mechanisms were all considered. The mechanisms of the diabetogenic effect of modern immunosuppressive drugs were analysed. The principles of pre- and post-transplantation screening for PTDM and optimal management strategies for patients with PTDM are presented. The current controversial issues concerning the various aspects of PTDM are discussed.

посттрансплантационный сахарный диабеттрансплантациявпервые выявленныйиммуносупрессивные препаратыцитохром Р-450сахароснижающие препаратыpost-transplantation diabetes mellitustransplantationnew onset diabetesimmunosuppressive agentscytochrome P-450hypoglycaemic agentsВведение
ПТСД (диагностируется через 30–45 дней после трансплантации)Симптомы диабета плюс случайное определение гликемии ≥11,1 ммоль/л (≥200 мг/дл) или глюкоза плазмы натощак ≥7,0 ммоль/л (≥126 мг/дл), или ≥11,1 ммоль/л (≥200 мг/дл) через 2 ч после ПГТТ, или HbA1c≥6,5%.
Предиабет- Нарушение гликемии натощак- Нарушение толерантности к глюкозе- Повышенный риск развития диабетаГлюкоза плазмы натощак 5,6–6,9 ммоль/л (100–126 мг/дл)Глюкоза плазмы натощак <7,0 ммоль/л и 7,8–11,1 ммоль/л через 2 ч после ПГТТHbA1c 5,7–6,4%
Эпидемиология
НемодифицируемыеУсловно модифицируемыеМодифицируемые
Этническая принадлежностьВозраст более 45 летМужской пол донораОтягощенная наследственность по сахарному диабетуHLA A28, A30, B42 и др.Несовместимость по HLA-антигенамИмеющееся отторжение в анамнезеПоликистоз почек?HCV-инфекцияЦМВ-инфекцияГипомагниемияНарушение углеводного обмена до или после трансплантацииИммуносупрессивная терапия:- ингибиторы кальциневрина- ингибиторы mTOR- кортикостероиды- индукционная терапия?Ожирение или другие компоненты метаболического синдрома
Название генаПолиморфизмNИсследованияСвязь с ПТСД
Аполипопротеин С-III (APOC3)Sstl110Rodrigo et al.Нет
Аполипопротеин Е (АРОЕ)ε2/ ε3/ ε4110Rodrigo et al.Нет
Интерферон-гамма (IFNG)+874278Babel et al.АА генотип связан с ПТСД
Интерлейкин 10 (IL10)-1082278Babel et al.Нет
Рецептор витамина D (VDR)TaqI70Numakura et al.ПТСД связан с TaqI
ApaIНет
BsmIНет
G866AНет
Цитохром P450 (CYP3A5)A6986G70Numakura et al.Нет
Ангиотензинпревращающий фермент (АСЕ)I/D70Numakura et al.Нет
42Rodríguez-Moreno et al.Нет
Ангиотензиноген (АGT)M235T42Rodríguez-Moreno et al.ТТ генотип связан с ПТСД
Интерлейкин 6 (IL6)-174 (G>C)349Bamoulid et al.CC генотип: снижение риска развития ПТСД
335Sánchez-Velasco et al.Нет
278Babel et al.Нет
Фактор некроза опухоли (TNF)G-238A61Gençtoy et al.(АА+GA) генотипы G-238A: высокий уровень инсулина натощак и HOMA-IR
-308278Babel et al.Нет
Т-специфичнотранскрипционный фактор 7(TCF7L2)rs7903146589Kang et al.OR CТ генотипа: 1,71
1076Ghisdal et al.OR CT генотипа: 1,7; TT генотипа: 2,42
234Kurzawski et al.Нет
303Yang et al.Нет
Семейство транспортеров растворенных веществ 30, член 8 (SLC30A8)rs13266634589Kangetal.OR CC генотипа: 1,96
Рекомбинантный белок человека (HHEX)rs1111875589Kang et al.OR CC генотипа: 1,81
rs7923837OR GG генотипа: 1,84
rs5015480OR CC генотипа: 1,97
Регуляторная субъединица-1 циклинзависимой киназы типа 5 (CDKAL1)rs10946398589Kang et al.OR CC генотипа: 2,02
Ингибитор циклинзависимой киназы 2A/2B (CDKN2A/B)rs10811661589Kang et al.OR TT генотипа: 1,66
Потенциал-зависимый калиевый канал 1, подсемейство KQT (KCNQ1)rs2237892589Kang et al.OR TT генотипа: 1,61
Кальпин 10 (CAPN10)rs5030952372Kurzawski et al.OR CT генотипа: 2,45
Ядерный фактор гепатоцита 4a (HNF4A)rs2144908303Yang et al.OR AA генотипа: 1,96
rs1884614OR TT генотипа: 2,44
Субстрат инсулинового рецептора-1 (IRS1)rs1801278303Yang et al.OR AA+AG генотипов: 2,71
Скрининг реципиентов с трансплантацией солидных органовВедение пациентов с ПТСД
КлассПрепаратЛекарственное взаимодействие
Первое поколение препаратов сульфонилмочевиныВсе препараты↑ концентрацию ЦсА
Второе поколение препаратов сульфонилмочевиныГлипизид, Гликлазид, Глибенкламид, Глимепирид↑ концентрацию ЦсА
ГликвидонНет
ГлинидыРепаглинид↑ концентрацию как репаглинида, так и ЦсА
Натеглинид↑ концентрацию как натеглинида, так и ЦсА
Ингибиторы α-глюкозидазыАкарбозаНет
БигуанидиныМетформинНет
ТиазолидиндионыПиоглитазонНет
РозиглитазонНет
Агонисты рецепторов ГПП-1ЭксенатидНет
Ингибиторы ДПП-4СитаглиптинМетаболизируется цитохромомP450*
ВилдаглиптинНет
СаксаглиптинМетаболизируется цитохромом Р450*
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The authors declare that there are no conflicts of interest present.