The potential of survivin as a non-invasive diagnostic marker for endometriosis in patients with type 1 diabetes mellitus

BACKGROUND: According to international data, about 5-10% of women of reproductive age suffer from this disease, while in women with chronic pelvic pain or infertility the incidence ranges from 35% to 50%. At the same time, women of reproductive age diagnosed with diabetes mellitus type 1 may also suffer from endometriosis, but asymptomatic or atypical in the initial stages of the disease, which varies considerably in duration, may be the cause of untimely diagnosis. Existing diagnostic methods in the form of bimanual examination, ultrasound, MRI, laparoscopic surgery, and even histologic verification do not allow to exclude with certainty the presence of the disease. AIM: The aim of this study was to investigate the prevalence and characteristics of endometriosis among patients with type 1 diabetes mellitus to develop a diagnostic prognostic model.

We carried out a retrospective analysis of medical records from the Gynecological Unit of the Second Department of Gynecology and Endocrinology and the Scientific Advisory Department of D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductive Medicine, St. Petersburg, Russia for the period of 2010–2021. The study cohort included cases of endometriosis in patients with type 1 diabetes mellitus recorded in inpatient or outpatient medical histories. Clinical characteristics of the prevalence of endometriosis in women with type 1 diabetes mellitus were based on an analysis of 2316 medical records in this patient group. The prospective cohort of the case-control study included 137 patients and involved the evaluation of survivin levels in serum on days 5–7 of the menstrual cycle in four study groups: type 1 diabetes mellitus in combination with endometriosis, endometriosis, type 1 diabetes mellitus, and healthy women of reproductive age. Additionally, we examined the gynecological history of patients. Statistical processing of the data obtained and predictive modeling were performed using a binary logistic regression analysis.

The prevalence of endometriosis among patients with type 1 diabetes mellitus was 1.11%. Risk indicators for the presence of endometriosis were determined based on risk factor values for patients with or without type 1 diabetes mellitus. Patient groups with a probability of having endometriosis exceeding 50% were identified, requiring diagnostic and therapeutic measures aimed at timely initiation of therapy.

Predicting the likelihood of endometriosis presence will enable timely preventive and therapeutic measures aimed at improving the patient’s quality of life.

Full Text About the authors Nelly Yu. Andreeva The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott Author for correspondence. Email: [email protected] ORCID iD: 0000-0002-1928-1266 SPIN-code: 3355-2646 Russian Federation, Saint Petersburg Maria I. Yarmolinskaya The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott Email: [email protected] ORCID iD: 0000-0002-6551-4147 SPIN-code: 3686-3605 MD, Dr. Sci. (Med.), Professor of the Russian Academy of Sciences Russian Federation, Saint PetersburgElena V. Misharina The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott Email: [email protected] ORCID iD: 0000-0002-0276-7112 SPIN-code: 7350-5674 MD, Cand. Sci. (Med.) Russian Federation, Saint PetersburgNatalia N. Tkachenko The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott Email: [email protected] ORCID iD: 0000-0001-6189-3488 SPIN-code: 9633-6701 Cand. Sci. (Biol.) Russian Federation, Saint PetersburgReferences - Magliano DJ, Boyko EB, Balkau B, et al. What is diabetes? In: IDF Diabetes Atlas. 10th edition. Ed. by D.J. Magliano, E.B. Boyko. Berkeley: Berkeley Communications; 2021. P. 13–18. - Dedov II, Shestakova MV, Vikulova OK, et al. Epidemiological characteristics of diabetes mellitus in the Russian Federation: clinical and statistical analysis according to the Federal diabetes register data of 01.01.2021. Diabetes mellitus. 2021;24(3):204–221. (In Russ.) doi: 10.14341/DM12759 - Simmen RCM, Brown DM, Quick CM, et al. Co-morbidity of type 1 diabetes and endometriosis: bringing a new paradigm into focus. J Endocrinol. 2019;243(3):R47–R57. doi: 10.1530/JOE-19-0248 - Yarmolinskaya MI, Aylamazyan EK. Genital’nyy endometrioz. Razlichnye grani problemy. Saint Petersburg: Eco-Vector; 2017. (In Russ.) - Osum KC, Burrack AL, Martinov T, et al. Interferon-gamma drives programmed death-ligand 1 expression on islet β cells to limit T cell function during autoimmune diabetes. Scientific Reports. 2018;8(1):8295. doi: 10.1038/s41598-018-26471-9 - Gueuvoghlanian-Silva BY, Bellelis P, Barbeiro DF, et al. Treg and NK cells related cytokines are associated with deep rectosigmoid endometriosis and clinical symptoms related to the disease. J Reprod Immunol. 2018;126:32–38. doi: 10.1016/j.jri.2018.02.003 - Kocbek V, Grandi G, Blank F, et al. TNFα-induced IKKβ complex activation influences epithelial, but not stromal cell survival in endometriosis. Mol Hum Repro. 2016;22(11):768–777. doi: 10.1093/molehr/gaw054 - Sánchez-Zamora YI, Juarez-Avelar I, Vazquez-Mendoza A, et al. Altered macrophage and dendritic cell response in MIF-/- mice reveals a role of MIF for inflammatory-Th1 response in type 1 diabetes. J Diabetes Res. 2016;216. doi: 10.1155/2016/7053963 - Mormile R, Vittori G. Type 1 diabetes in women with endometriosis: what is the risk of occurence? Pediatr Endocr Met. 2013;24:1007-1009. doi: 10.1525/ipem-2013-0134 - Bianco B, Filipchiuk C, Christofolini DM, et al. The role of survivin in the pathogenesis of endometriosis. Minerva Med. 2020;111(1):21–32. doi: 10.23736/S0026-4806.19.06358-4 - Filipchiuk C, Laganà AS, Beteli R, et al. BIRC5/survivin expression as a non-invasive biomarker of endometriosis. Diagnostics. 2020;10(8):533. doi: 10.3390/diagnostics10080533 - Bulun SE, Yilmaz BD, Sison C, et al. Endometriosis. Endocr Rev. 2019;40(4):1048–1079. doi: 10.1210/er.2018-00242 - Arion K, Orr NL, Noga H, et al. A quantitative analysis of sleep quality in women with endometriosis. J Womens Health. 2020; 29(9):1209–1215. doi: 10.1089/jwh.2019.8008 - Moradi Y, Shams-Beyranvand M, Khateri S, et al. A systematic review on the prevalence of endometriosis in women. Indian J Med Res. 2021;154(3):446–454. doi: 10.4103/ijmr.IJMR_817_18 - Shigesi N, Kvaskoff M, Kirtley S, et al. The association between endometriosis and autoimmune diseases: a systematic review and meta-analysis. Hum Reprod Update. 2019;25(4):486–503. doi: 10.1093/humupd/dmz014 - Moradi Y, Shams-Beyranvand M, Khateri S, et al. A systematic review on the prevalence of endometriosis in women. Indian J Med Res. 2021;154(3):446–454. doi: 10.4103/ijmr.IJMR_817_18 - Ueda M, Yamashita Y, Takehara M, et al. Survivin gene expression in endometriosis. J Clin Endocrinol Metab. 2002;87(7):3452–3459. doi: 10.1210/jcem.87.7.8682 - Liman N, Alan E, Bayram GK, et al. Expression of survivin, Bcl-2 and Bax proteins in the domestic cat (Felis catus) endometrium during the oestrus cycle. Reprod Domest Anim. 2013;48(1):33–45. doi: 10.1111/j.1439-0531.2012.02021.x - Liu N, Zhao N, Chen L, et al. Survivin contributes to the progression of diabetic retinopathy through HIF-1α pathway. Int J Clin Exp Pathol. 2015;8(8):9161–9167. - Abu-El-Asrar AM, Dralands L, Missotten L, et al. Expression of apoptosis markers in the retinas of human subjects with diabetes. Invest Ophthalmol Vis Sci. 2004;45(8):2760–2766. doi: 10.1167/iovs.03-1392 - Janša V, Pušić Novak M, Ban Frangež H, et al. TGFBI as a candidate biomarker for non-invasive diagnosis of early-stage endometriosis. Hum Reprod. 2023;38(7):1284–1296. doi: 10.1093/humrep/dead091 - Goulielmos GN, Matalliotakis M, Matalliotaki C, et al. Endometriosis research in the omics era. Gene. 2020;741. doi: 10.1016/j.gene.2020.144545 - Anastasiu CV, Moga MA, Neculau EA, et al. Biomarkers for the noninvasive diagnosis of endometriosis: state of the art and future perspectives. Int J Mol Sci. 2020;21(5). doi: 10.3390/ijms21051750 - Nisenblat V, Bossuyt PM, Shaikh R, et al. Blood biomarkers for the non-invasive diagnosis of endometriosis. Cochrane Database Syst Rev. 2016;2016(5). doi: 10.1002/14651858.CD012179