Проблемы социальной гигиены, здравоохранения и истории медициныПроблемы социальной гигиены, здравоохранения и истории медицины0869-866X2412-2106Joint-Stock Company Chicot210310.32687/0869-866X-2023-31-s2-1189-1196Научная статьяАКТУАЛЬНЫЕ СТРАТЕГИИ ПРОФИЛАКТИКИ САХАРНОГО ДИАБЕТА 1-го ТИПА: ОБЗОР ЗАРУБЕЖНОЙ ЛИТЕРАТУРЫГречушкинаН. А.ГБУ «НИИ организации здравоохранения и медицинского менеджмента Департамента здравоохранения города Москвы», 115088, Москва, Россия0212202331\S21189119605082025Copyright © 1970, АО "Шико"1970Точная этиология и механизмы, провоцирующие развитие сахарного диабета 1-го типа (СД1), до конца не изучены, но появляется всё больше научных данных, подтверждающих, что поражение островковых клеток (β-клеток) поджелудочной железы инициируется факторами окружающей среды у генетически восприимчивых людей. В настоящее время основная тактика лечения СД1 на стадии клинических проявлений строится на заместительной инсулинотерапии. Внедрение в медицинскую практику современных препаратов инсулина и устройств для его доставки, а также систем непрерывного мониторинга глюкозы не избавляет пациентов от необходимости пожизненного приёма этого гормона. Поэтому разработка методов профилактики СД1 остаётся главной задачей исследований в области диабета. Статья подготовлена на основе обзора актуальных публикаций из библиографической базы данных PubMed. В работе обсуждаются стратегии, нацеленные на устранение экологических триггеров, современные методы регулирования иммунного ответа, нецелевые эффекты вакцины БЦЖ, общие принципы персонализированной профилактики.literature reviewtype-1 diabetespreventionβ-cellsautoimmune diseasesобзор литературыдиабет 1-го типапрофилактикаβ-клеткиаутоиммунные заболевания[Insel R. A., Dunne J. L., Atkinson M. A. et al. Staging presymptomatic type 1 diabetes: a scientific statement of JDRF, the Endocrine Society, and the American Diabetes Association // Diabetes Care. 2015. Vol. 38, N 10. P. 1964–1974. DOI: 10.2337/dc15-1419][Podichetty J. T., Lang P., O'Doherty I. M. et al. Leveraging real world data for EMA qualification of a model-based biomarker tool to optimize type-1 diabetes prevention studies // Clin. Pharmacol. Ther. 2022. Vol. 111, N 5. P. 1133–1141. DOI: 10.1002/cpt.2559][McLaughlin K. A., Richardson C. C., Ravishankar A. et al. Identification of Tetraspanin-7 as a target of autoantibodies in type 1 diabetes // Diabetes. 2016. Vol. 65, N 6. P. 1690–1698. DOI: 10.2337/db15-1058][Carr A. L.J., Evans-Molina C., Oram RA. Precision medicine in type 1 diabetes // Diabetologia. 2022. Vol. 65, N 11. P. 1854–1866. DOI: 10.1007/s00125-022-05778-3][Chung W. K., Erion K., Florez J. C. et al. Precision medicine in diabetes: a Consensus Report from the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) // Diabetologia. 2020. Vol. 63, N 9. P. 1671–1693. DOI: 10.1007/s00125-020-05181-w][Gradisteanu Pircalabioru G., Corcionivoschi N., Gundogdu O. et al. Dysbiosis in the development of type i diabetes and associated complications: from mechanisms to targeted gut microbes manipulation therapies // Int. J. Mol. Sci. 2021. Vol. 22, N 5. P. 2763. DOI: 10.3390/ijms22052763][Alcazar O., Hernandez L. F., Nakayasu E. S. et al. Parallel multi omics in high risk subjects for the identification of integrated biomarker signatures of type 1 diabetes // Biomolecules. 2021. Vol. 11, N 3. P. 383. DOI: 10.3390/biom11030383][Xhonneux L. P., Knight O., Lernmark Å. et al. Transcriptional networks in at risk individuals identify signatures of type 1 diabetes progression // Sci. Transl. Med. 2021. Vol. 13. P. eabd5666. DOI: 10.1126/scitranslmed.abd5666][Rodriguez-Calvo T. Enterovirus infection and type 1 diabetes: Unraveling the crime scene // Clin. Exp. Immunol. 2019. Vol. 195. P. 15–24. DOI: 10.1111/cei.13223][Faulkner C. L., Luo Y. X., Isaacs S. et al. The virome in early life and childhood and development of islet autoimmunity and type 1 diabetes: a systematic review and meta analysis of observational studies // Rev. Med. Virol. 2020. P. e2209. DOI: 10.1002/rmv.2209][Blanter M., Sork H., Tuomela S., Flodström-Tullberg M. Genetic and environmental interaction in type 1 diabetes: a relationship between genetic risk alleles and molecular traits of enterovirus infection? // Curr. Diabetes Rep. 2019; Vol. 19. P. 82. DOI: 10.1007/s11892-019-1192-8][Paun A., Yau C., Meshkibaf S. et al. Association of HLA dependent islet autoimmunity with systemic antibody responses to intestinal commensal bacteria in children // Sci. Immunol. 2019. Vol. 4. P. eaau8125. DOI: 10.1126/sciimmunol.aau8125][Isaacs S. R., Foskett D. B., Maxwell A. J. et al. Viruses and type 1 diabetes: from enteroviruses to the virome // Microorganisms. 2021. Vol. 9, N 7. P. 1519. DOI: 10.3390/microorganisms9071519][Root-Bernstein R., Chiles K., Huber J. et al. Clostridia and enteroviruses as synergistic triggers of type 1 diabetes mellitus // Int. J. Mol. Sci. 2023. Vol. 24, N 9. P. 8336. DOI: 10.3390/ijms24098336][Nekoua M. P., Mercier A., Alhazmi A. et al. Fighting enteroviral infections to prevent type 1 diabetes // Microorganisms. 2022. Vol. 10, N 4. P. 768. DOI: 10.3390/microorganisms10040768][Ishmukhametov A. A., Siniugina А.А., Chumakov K. M. The development of polio vaccines: the current update (review) // Sovremennye tehnologii v medicine. 2019. Vol. 11, N 4. P. 200–215. DOI: 10.17691/stm2019.11.4.22][Hu Y., Zeng G., Chu K. et al. Five-year immunity persistence following immunization with inactivated enterovirus 71 type (EV71) vaccine in healthy children: a further observation // Hum. Vaccines Immunother. 2018. Vol. 14. P. 1517–1523. DOI: 10.1080/21645515.2018][Stone V. M., Hankaniemi M. M., Laitinen O. H. et al. A hexavalent Coxsackievirus B vaccine is highly immunogenic and has a strong protective capacity in mice and nonhuman primates // Sci. Adv. 2020. Vol. 6, N 19. P. eaaz2433. DOI: 10.1126/sciadv.aaz2433][Hankaniemi M. M., Baikoghli M. A., Stone V. M. et al. Structural Insight into CVB3-VLP Non-Adjuvanted Vaccine // Microorganisms. 2020. Vol. 8, N 9. P. 1287. DOI: 10.3390/microorganisms8091287][Beik P., Ciesielska M., Kucza M. et al. Prevention of type 1 diabetes: past experiences and future opportunities // J. Clin. Med. 2020. Vol. 9, N 9. P. 2805. DOI: 10.3390/jcm9092805][Movahed A., Raj P., Nabipour I. et al. Efficacy and safety of resveratrol in type 1 diabetes patients: a two-month preliminary exploratory trial // Nutrients. 2020. Vol. 12, N 1. P. 161. DOI: 10.3390/nu12010161][Ku C. R., Lee H. J., Kim S. K. et al. Resveratrol prevents streptozotocin induced diabetes by inhibiting the apoptosis of pancreatic β cell and the cleavage of poly (ADP-ribose) polymerase // Endocr. J. 2012. Vol. 59, N 2. P. 103–109. DOI: 10.1507/endocrj.ej11-0194][Franić Z., Franić Z., Vrkić N. et al. Effect of extract from Boswellia serrata gum resin on decrease of GAD65 autoantibodies in a patient with latent autoimmune diabetes in adults // Altern. Ther. Health Med. 2020. Vol. 26, N 5. P. 38–40.][Gavin P. G., Hamilton-Williams E. E. The gut microbiota in type 1 diabetes: friend or foe? // Curr. Opin. Endocrinol. Diabetes Obes. 2019. Vol. 26, N 4. P. 207–212. DOI: 10.1097/MED.0000000000000483][Hansen C. H.F., Krych L., Nielsen D. S. et al. Early life treatment with vancomycin propagates Akkermansia muciniphila and reduces diabetes incidence in the NOD mouse // Diabetologia. 2012. Vol. 55. P. 2285–2294.][Candon S., Perez-Arroyo A., Marquet C. et al. Antibiotics in early life alter the gut microbiome and increase disease incidence in a spontaneous mouse model of autoimmune insulin-dependent diabetes // PLoS One. 2015. Vol. 10. P. e0125448.][Hu Y., Jin P., Peng J. et al. Different immunological responses to early-life antibiotic exposure affecting autoimmune diabetes development in NOD mice // J. Autoimmun. 2016. Vol. 72. P. 47–56. DOI: 10.1016/j.jaut.2016.05.001][Livanos A. E., Greiner T. U., Vangay P. et al. Antibiotic-mediated gut microbiome perturbation accelerates development of type 1 diabetes in mice // Nat. Microbiol. 2016. Vol. 1, N 11. P. 16140. DOI: 10.1038/nmicrobiol.2016.140][Zhang Y., Lee A. S., Shameli A. et al. TLR9 blockade inhibits activation of diabetogenic CD8+ T cells and delays autoimmune diabetes // J. Immunol. 2010. Vol. 184. P. 5645–5653.][Gülden E., Ihira M., Ohashi A. et al. Toll-like receptor 4 deficiency accelerates the development of insulin-deficient diabetes in non-obese diabetic mice // PLoS One. 2013. Vol. 8. P. e75385. DOI: 10.1371/journal.pone.0075385][Alkanani A. K., Hara N., Lien E. et al. Induction of diabetes in the RIP-B7.1 mouse model is critically dependent on TLR3 and MyD88 pathways and is associated with alterations in the intestinal microbiome // Diabetes. 2013. Vol. 63. P. 619–631.][Zhou H., Sun L., Zhang S. et al. Evaluating the causal role of gut microbiota in type 1 diabetes and its possible pathogenic mechanisms // Front. Endocrinol. 2020. Vol. 11. P. 125. DOI: 10.3389/fendo.2020.00125][Warshauer J. T., Bluestone J. A., Anderson M. S. New frontiers in the treatment of type 1 diabetes // Cell Metab. 2020. Vol. 31, N 1. P. 46–61. DOI: 10.1016/j.cmet.2019.11.017][Herold K. C., Bundy B. N., Long S. A. et al. An anti-CD3 antibody, Teplizumab, in relatives at risk for type 1 diabetes // N. Engl. J. Med. 2019. Vol. 381, N 7. P. 603–613. DOI: 10.1056/NEJMoa1902226][Sims E. K., Cuthbertson D., Herold K. C., Sosenko J. M. The deterrence of rapid metabolic decline within 3 months after Teplizumab treatment in individuals at high risk for type 1 diabetes // Diabetes. 2021. Vol. 70, N 12. P. 2922–2931. DOI: 10.2337/db21-0519][Nourelden A. Z., Elshanbary A. A., El-Sherif L. et al. Safety and efficacy of Teplizumab for Treatment of type one diabetes mellitus: a systematic review and meta analysis // Endocr. Metab. Immune Disord. Drug Targets. 2021. Vol. 21, N 10. P. 1895–1904. DOI: 10.2174/1871530320999201209222921][Russell W. E., Bundy B. N., Anderson M. S. et al. Abatacept for delay of type 1 diabetes progression in stage 1 relatives at risk: a randomized, double masked, controlled trial // Diabetes Care. 2023. Vol. 46, N 5. P. 1005–1013. DOI: 10.2337/dc22-2200][Guyot M., Simon T., Ceppo F. et al. Pancreatic nerve electrostimulation inhibits recent-onset autoimmune diabetes // Nat. Biotechnol. 2019. Vol. 37, N 12. P. 1446–1451. DOI: 10.1038/s41587-019-0295-8][Thompson P. J., Shah A., Ntranos V. et al. Targeted elimination of senescent beta cells prevents type 1 diabetes // Cell Metab. 2019. Vol. 29, N 5. P. 1045–1060.e10. DOI: 10.1016/j.cmet.2019.01.021][Chaillous L., Lefèvre H., Thivolet C. et al. Oral insulin administration and residual beta-cell function in recent-onset type 1 diabetes: a multicentre randomised controlled trial // Diabète Insuline Orale group. Lancet. 2000. Vol. 356, N 9229. P. 545–549. DOI: 10.1016/s0140-6736(00)02579–4][Fourlanos S., Perry C., Gellert S. A. et al. Evidence that nasal insulin induces immune tolerance to insulin in adults with autoimmune diabetes // Diabetes. 2011. Vol. 60, N 4. P. 1237–1245. DOI: 10.2337/db10-1360][Alhadj A. M., Liu Y. F., Arif S. et al. Metabolic and immune effects of immunotherapy with proinsulin peptide in human new-onset type 1 diabetes // Sci. Transl. Med. 2017. Vol. 9, N 402. P. eaaf7779. DOI: 10.1126/scitranslmed.aaf7779][Ludvigsson J., Krisky D., Casas R. et al. GAD65 antigen therapy in recently diagnosed type 1 diabetes mellitus // N. Engl. J. Med. 2012. Vol. 366, N 5. P. 433–442. DOI: 10.1056/NEJMoa1107096][Ziegler A. G., Achenbach P., Berner R. et al. Oral insulin therapy for primary prevention of type 1 diabetes in infants with high genetic risk: the GPPAD-POInT (global platform for the prevention of autoimmune diabetes primary oral insulin trial) study protocol // BMJ Open. 2019. Vol. 9, N 6. P. e028578. DOI: 10.1136/bmjopen-2018-028578][Sosenko J. M., Skyler J. S., Herold K. C. et al. Slowed metabolic decline after 1 year of oral insulin treatment among individuals at high risk for type 1 diabetes in the Diabetes Prevention Trial-Type 1 (DPT-1) and TrialNet Oral Insulin Prevention Trials // Diabetes. 2020. Vol. 69, N 8. P. 1827–1832. DOI: 10.2337/db20-0166][Ludvigsson J. Autoantigen treatment in type 1 diabetes: unsolved questions on how to select autoantigen and administration route // Int. J. Mol. Sci. 2020. Vol. 21, N 5. P. 1598. DOI: 10.3390/ijms21051598][Zhou X., Zhang S., Yu F. et al. Tolerogenic vaccine composited with islet-derived multipeptides and cyclosporin A induces pTreg and prevents Type 1 diabetes in murine model // Hum. Vaccin. Immunother. 2020. Vol. 16, N 2. P. 240–250. DOI: 10.1080/21645515.2019.1616504][Khan F. U., Khongorzul P., Raki A. A. et al. Dendritic cells and their immunotherapeutic potential for treating type 1 diabetes // Int. J. Mol. Sci. 2022. Vol. 23. P. 4885. DOI: 10.3390/ijms23094885][Phillips B. E., Garciafigueroa Y., Engman C. et al. Tolerogenic dendritic cells and T-regulatory cells at the clinical trials crossroad for the treatment of autoimmune disease; emphasis on type 1 diabetes therapy // Front. Immunol. 2019. Vol. 10. P. 148. DOI: 10.3389/fimmu.2019.00148][Serra P., Santamaria P. Peptide-MHC-based nanomedicines for the treatment of autoimmunity: engineering, mechanisms, and diseases // Front. Immunol. 2021. Vol. 11. P. 621774. DOI: 10.3389/fimmu.2020.621774][Postigo-Fernandez J., Firdessa-Fite R., Creusot R. J. Preclinical evaluation of a precision medicine approach to DNA vaccination in type 1 diabetes // Proc. Natl. Acad. Sci. USA. 2022. Vol. 119, N 15. P. e2110987119. DOI: 10.1073/pnas.2110987119][Kühtreiber W. M., Faustman D. L. BCG therapy for type 1 diabetes: restoration of balanced immunity and metabolism // Trends. Endocrinol. Metab. 2019. Vol. 30, N 2. P. 80–92. DOI: 10.1016/j.tem.2018.11.006][Takahashi H., Kühtreiber W. M., Keefe R. C. et al. BCG vaccinations drive epigenetic changes to the human T cell receptor: Restored expression in type 1 diabetes // Sci. Adv. 2022. Vol. 8, N 46. P. eabq7240. DOI: 10.1126/sciadv.abq7240][Dias H. F., Mochizuki Y., Kühtreiber W. M. et al. Bacille Calmette Guerin (BCG) and prevention of types 1 and 2 diabetes: results of two observational studies // PLoS One. 2023. Vol. 18, N 1. P. e0276423. DOI: 10.1371/journal.pone.0276423]