Document Type : Original Research Article
Authors
- Nur Rochmah 1
- Ike Wahyu Triastuti 1
- Wika Yuli Deakandi 2
- Roedi Irawan 1
- Muhammad Faizi 1
- Anang Endaryanto 1
1 Department of Child Health, Faculty of Medicine Universitas Airlangga, Dr. Soetomo General Academic Hospital, Surabaya, Indonesia
2 Faculty of Medicine, Universitas Islam Malang, Malang, East Java, Indonesia
10.48309/ecc.2024.434749.1746
Abstract
Type 1 diabetes mellitus (T1DM) is an autoimmune disease that often affects children. This condition is caused by a failure in peripheral tolerogenic mechanisms. The role of transforming growth factor-beta 1 (TGF-β) in this mechanism is still controversial. This study evaluated the association between serum TGF-β levels and T1DM in children. This study may serve as a foundation for exploring the potential benefits of TGF-β knowledge, such as the discovery of novel therapeutics or the prevention of complications associated with T1DM. A case-control study was conducted with 26 children with T1DM and 26 without T1DM (as control) at the General and Endocrinology Pediatric outpatient clinic and pediatric ward of Dr Soetomo Surabaya Hospital from October 2020 to March 2021. Differences in serum TGF-β levels were determined using the Mann-Whitney U test. The mean age of onset was 7.23±4.11 years, and the time duration of diagnosis was 6.35±3.45 years. TGF-β was lower in T1DM than in the control group (1.36, 95% CI 0.44–3.42 ng/mL vs. 3.54, 95% CI 2.01–4.00 ng/mL; p<0.001). The serum TGF-β levels were not significantly associated with the duration of T1DM and c-peptide (p=0.481; p=0.235). Children with T1DM may have lowered immunity due to decreased TGF-β.
Graphical Abstract
)
Keywords
Main Subjects
[1] a) P. Saeedi, I. Petersohn, P. Salpea, B. Malanda, S. Karuranga, N. Unwin, S. Colagiuri, L. Guariguata, A.A. Motala, K. Ogurtsova, Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, Diabetes Research and Clinical Practice, 2019, 157, 107843. [Crossref], [Google Scholar], [Publisher]; b) K.S. Aminu, A. Uzairu, S.E. Abechi, G.S. Adamu, A.B. Umar, A search for novel antidiabetic agents using ligand-based drug design and molecular docking studies employing human intestinal maltase-glucoamylase as model enzyme, Advanced Journal of Chemistry, Section A, 2023, 6, 155-171. [Crossref], [Google Scholar], [Publisher]; c) S. Ishrat, A. Zafar, F. Hameed, S. Bashir, S. Khan, R. Hafeez, Vitamin C intervention in type 2 diabetes mellitus: A comprehensive analysis of lipid profile and glycemic parameters, Journal of Medicinal and Chemical Sciences, 2024, 7, 744-752. [Crossref], [Pdf], [Publisher]; d) L. Romaniuk, A. Levchenko, Study of the influence of intestinal microbiota on the immune response in allergic diseases manifested by food allergy and urticaria, Journal of Medicinal and Chemical Sciences, 2024, 7, 565-578. [Crossref], [Pdf], [Publisher]; e) H. Susianti, E.S. Dewi, M. Afiyanti, C.P. Susanto, S. Ramawati, A. Aprilia, Kusworini Handono, Effect of immune cell ageing on humoral immunity responses post-COVID-19 vaccination, Journal of Medicinal and Chemical Sciences, 2024, 7, 392-401. [Crossref], [Pdf], [Publisher]; f) F. Handajani, N. Nabil, Effect of pangasius hypophthalmus fish extract on blood sugar and uric acid levels in alloxan-induced rattus norvegicus, Journal of Medicinal and Chemical Sciences, 2024, 7, 124-131. [Crossref], [Pdf], [Publisher]
[2] A.B. Pulungan, G. Fadiana, D. Annisa, Type 1 diabetes mellitus in children: experience in Indonesia, Clinical Pediatric Endocrinology, 2021, 30, 11-18. [Crossref], [Google Scholar], [Publisher]
[3] M. Rewers, J. Ludvigsson, Environmental risk factors for type 1 diabetes, The Lancet, 2016, 387, 2340-2348. [Crossref], [Google Scholar], [Publisher]
[4] J. Lu, J. Liu, L. Li, Y. Lan, Y. Liang, Cytokines in type 1 diabetes: mechanisms of action and immunotherapeutic targets, Clinical & Translational Immunology, 2020, 9, e1122. [Crossref], [Google Scholar], [Publisher]
[5] K.C. Mekala, A.G. Bertoni, Epidemiology of diabetes mellitus, Transplantation, bioengineering, and regeneration of the endocrine pancreas, Elsevier, 2020, 1, 49-58. [Crossref], [Google Scholar], [Publisher]
[6] S.T. Azar, I. Salti, M.S. Zantout, S. Major, Alterations in plasma transforming growth factor β in normoalbuminuric type 1 and type 2 diabetic patients, The Journal of Clinical Endocrinology & Metabolism, 2000, 85, 4680-4682. [Crossref], [Google Scholar], [Publisher]
[7] H.L. Wang, L. Wang, C.Y. Zhao, H.Y. Lan, Role of TGF-beta signaling in beta cell proliferation and function in diabetes, Biomolecules, 2022, 12, 373. [Crossref], [Google Scholar], [Publisher]
[8] V. Saxena, D.W. Lienesch, M. Zhou, R. Bommireddy, M. Azhar, T. Doetschman, R.R. Singh, Dual roles of immunoregulatory cytokine TGF-β in the pathogenesis of autoimmunity-mediated organ damage, The Journal of Immunology, 2008, 180, 1903-1912. [Crossref], [Google Scholar], [Publisher]
[9] A.G. Ziegler, M. Rewers, O. Simell, T. Simell, J. Lempainen, A. Steck, C. Winkler, J. Ilonen, R. Veijola, M. Knip, Seroconversion to multiple islet autoantibodies and risk of progression to diabetes in children, Jama, 2013, 309, 2473-2479. [Crossref], [Google Scholar], [Publisher]
[10] Y. Jin, A. Sharma, S. Bai, C. Davis, H. Liu, D. Hopkins, K. Barriga, M. Rewers, J.-X. She, Risk of type 1 diabetes progression in islet autoantibody-positive children can be further stratified using expression patterns of multiple genes implicated in peripheral blood lymphocyte activation and function, Diabetes, 2014, 63, 2506-2515. [Crossref], [Google Scholar], [Publisher]
[11] F. Heydarpour, S. Sajadimajd, E. Mirzarazi, P. Haratipour, T. Joshi, M.H. Farzaei, H. Khan, J. Echeverría, Involvement of TGF-β and autophagy pathways in pathogenesis of diabetes: a comprehensive review on biological and pharmacological insights, Frontiers in Pharmacology, 2020, 11, 498758. [Crossref], [Google Scholar], [Publisher]
[12] A. Roohi, M. Tabrizi, F. Abbasi, A. Ataie-Jafari, B. Nikbin, B. Larijani, M. Qorbani, A. Meysamie, H. Asgarian-Omran, B. Nikmanesh, Serum IL-17, IL-23, and TGF-β levels in type 1 and type 2 diabetic patients and age-matched healthy controls, BioMed Research International, 2014, 2014. [Crossref], [Google Scholar], [Publisher]
[13] Y.c. Qiao, J. Shen, X.z. Hong, L. Liang, C.s. Bo, Y. Sui, H.l. Zhao, Changes of regulatory T cells, transforming growth factor-beta and interleukin-10 in patients with type 1 diabetes mellitus: A systematic review and meta-analysis, Clinical Immunology, 2016, 170, 61-69. [Crossref], [Google Scholar], [Publisher]
[14] K. Zorena, E. Malinowska, D. Raczyńska, M. Myśliwiec, K. Raczyńska, Serum concentrations of transforming growth factor-Beta 1 in predicting the occurrence of diabetic retinopathy in juvenile patients with type 1 diabetes mellitus, Journal of Diabetes Research, 2013, 2013. [Crossref], [Google Scholar], [Publisher]
[15] M. Halminen, O. Simell, M. Knip, J. Ilonen, Cytokine expression in unstimulated PBMC of children with type 1 diabetes and subjects positive for diabetes‐associated autoantibodies, Scandinavian Journal of Immunology, 2001, 53, 510-513. [Crossref], [Google Scholar], [Publisher]
[16] A. Szypowska, A. Stelmaszczyk-Emmel, U. Demkow, W. Łuczyński, Low frequency of regulatory T cells in the peripheral blood of children with type 1 diabetes diagnosed under the age of five, Archivum Immunologiae Et Therapiae Experimentalis, 2012, 60, 307-313. [Crossref], [Google Scholar], [Publisher]
[17] A. Ninić, D. Bojanin, M. Sopić, M. Mihajlović, J. Munjas, T. Milenković, A. Stefanović, J. Vekić, V. Spasojević-Kalimanovska, Transforming growth factor-β1 and receptor for advanced glycation end products gene expression and protein levels in adolescents with type 1 diabetes mellitus, Journal of Clinical Research in Pediatric Endocrinology, 2021, 13, 61. [Crossref], [Google Scholar], [Publisher]
[18] S. Sanjabi, S.A. Oh, M.O. Li, Regulation of the immune response by TGF-β: from conception to autoimmunity and infection, Cold Spring Harbor Perspectives in Biology, 2017, 9, a022236. [Crossref], [Google Scholar], [Publisher]
[19] V. Bonfiglio, C.B.M. Platania, F. Lazzara, F. Conti, C. Pizzo, M. Reibaldi, A. Russo, M. Fallico, E. Ortisi, F. Pignatelli, TGF-β serum levels in diabetic retinopathy patients and the role of anti-VEGF therapy, International Journal of Molecular Sciences, 2020, 21, 9558. [Crossref], [Google Scholar], [Publisher]
[20] N. Gomez-Lopera, N. Pineda-Trujillo, P.A. Diaz-Valencia, Correlating the global increase in type 1 diabetes incidence across age groups with national economic prosperity: A systematic review, World Journal of Diabetes, 2019, 10, 560. [Crossref], [Google Scholar], [Publisher]
[21] N. Rochmah, M. Faizi, Y. Hisbiyah, I.W. Triastuti, G. Wicaksono, A. Endaryanto, Soetjipto, Quality of life differences in pre-and post-educational treatment in type 1 diabetes mellitus during COVID-19, Diabetes, Metabolic Syndrome and Obesity, 2021, 14, 2905-2911. [Crossref], [Google Scholar], [Publisher]
[22] K.F.B. Gomes, C. Semzezem, R. Batista, R.T. Fukui, A.S. Santos, M.R. Correia, M.R. Passos-Bueno, M.E.R.d. Silva, Importance of zinc transporter 8 autoantibody in the diagnosis of type 1 diabetes in Latin Americans, Scientific Reports, 2017, 7, 207. [Crossref], [Google Scholar], [Publisher]
[23] A. Bhatty, S. Baig, A. Fawwad, Z.E. Rubab, M.A. Shahid, N. Waris, Association of zinc transporter-8 autoantibody (ZnT8A) with type 1 diabetes mellitus, Cureus, 2020, 12. [Crossref], [Google Scholar], [Publisher]
[24] A.C.C. Braga de Souza, J.S. Felício, C.C. Koury, J.F.A. Neto, K.B. Miléo, F.M. Santos, C.A. Negrato, A.R.B. Motta, D.D. Silva, T.P. Arbage, Health-related quality of life in people with type 1 Diabetes Mellitus: data from the Brazilian Type 1 Diabetes Study Group, Health and Quality of Life Outcomes, 2015, 13, 1-9. [Crossref], [Google Scholar], [Publisher]
[25] Y.J. Park, S.A. Yoo, W.U. Kim, Role of endoplasmic reticulum stress in rheumatoid arthritis pathogenesis, Journal of Korean Medical Science, 2014, 29, 2. [Crossref], [Google Scholar], [Publisher]
[26] A.K. Kiani, P. John, A. Bhatti, A. Zia, G. Shahid, P. Akhtar, X. Wang, F.Y. Demirci, M.I. Kamboh, Association of 32 type 1 diabetes risk loci in Pakistani patients, Diabetes Research and Clinical Practice, 2015, 108, 137-142. [Crossref], [Google Scholar], [Publisher]
[27] P. Achenbach, V. Lampasona, U. Landherr, K. Koczwara, S. Krause, H. Grallert, C. Winkler, M. Pflüger, T. Illig, E. Bonifacio, Autoantibodies to zinc transporter 8 and SLC30A8 genotype stratify type 1 diabetes risk, Diabetologia, 2009, 52, 1881-1888. [Crossref], [Google Scholar], [Publisher]
)