Understanding the Genetic and Environmental Factors Contributing to Type 1 Diabetes

Dr. Surayya Khan; Dr. Muhammad  Usama; Dr. Rizwan  Ali; Dr. Muhammad  Gulfam; Dr. Kumail  Haider; Dr. Reemanta Asghar

doi:10.62497/IRABCS.2024.59

Authors

Dr. Surayya Khan Khalifa Gulnawaz Hospital Bannu Author
Dr. Muhammad Usama Khalifa Gulnawaz Hospital Bannu Author
Dr. Rizwan Ali Khalifa Gulnawaz Hospital Bannu Author
Dr. Muhammad Gulfam Bannu Medical College Author https://orcid.org/0009-0006-5762-8394
Dr. Kumail Haider POF Hospital WahCantt, Rawalpindi Author https://orcid.org/0009-0002-9563-3291
Dr. Reemanta Asghar Khyber Medical College, Peshawar Author https://orcid.org/0009-0006-5962-0767

DOI:

https://doi.org/10.62497/IRABCS.2024.59

Keywords:

Type 1 diabetes, HLA alleles, non-HLA loci, environmental factors, DNA methylation, epigenetics, autoimmune disease, genetic predisposition

Abstract

Introduction: Complex autoimmune illness type 1 diabetes (T1D) is affected by epigenetic, environmental, and hereditary elements. Good preventative and treatment plans depend on an awareness of these connections. The relationships among epigenetic changes in T1D development, environmental exposures, and genetic predispositions are examined in this work.

Methodology: From June 2022 until June 2024, Lady Reading Hospital (LRH) in Peshawar carried out a case-control study there were 88 individuals in all, 44 healthy controls and 44 diagnosed T1D patients. Data on demographic and clinical traits, family history, and environmental exposures as well as on With an eye toward non-HLA loci (PTPN22, INS) and HLA class II alleles (DR3-DQ2, DR4-DQ8), genetic study Examined were particular gene DNA methylation patterns (PTPN2, FOXP3). Chi-square tests, t-tests, odds ratios, and logistic regression comprised the statistical analyses.

Results: T1D patients had significantly higher frequencies of DR3-DQ2 (63.6%) and DR4-DQ8 (59.1%) compared to controls (22.7% and 27.3%, p < 0.001). T1D patients (45.5% and 40.9%) also more often had non-HLA loci PTPN22 and INS than controls (18.2% and 13.6%, p = 0.01). T1D was substantially correlated with environmental elements including enteroviral infections (50.0% vs. 18.2%, p = 0.002), early exposure to cow's milk (59.1% vs. 31.8%, p = 0.01), gluten (54.5% vs. 27.3%, p = 0.01), and changed gut microbiota (68.2% vs. 31.8%, p In T1D patients, epigenetic analysis identified hypermethylation of PTPN2 (60.0% vs. 20.0%, p = 0.01) and hypomethylation of FOXP3 (50.0% vs. 10.0%, p = 0.02).

Conclusion: This work validates in T1D the functions of epigenetic changes, environmental triggers, and genetic predisposition. The interactions among these elements underline the multifaceted character of T1D and imply that thorough interventions should target environmental as well as genetic elements.

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Author Biography

Dr. Muhammad Usama, Khalifa Gulnawaz Hospital Bannu

References

Esposito S, Toni G, Tascini G, Santi E, Berioli MG, Principi N. Environmental factors associated with type 1 diabetes. Frontiers in endocrinology. 2019 Aug 28;10:592. https://doi.org/10.3389/fendo.2019.00592

DiMeglio LA, Evans-Molina C, Oram RA. Type 1 diabetes. The Lancet. 2018 Jun 16;391(10138):2449-62.

Dedrick S, Sundaresh B, Huang Q, Brady C, Yoo T, Cronin C, Rudnicki C, Flood M, Momeni B, Ludvigsson J, Altindis E. The role of gut microbiota and environmental factors in type 1 diabetes pathogenesis. Frontiers in endocrinology. 2020 Feb 26;11:78. https://doi.org/10.3389/fendo.2020.00078

Norris JM, Johnson RK, Stene LC. Type 1 diabetes—early life origins and changing epidemiology. The lancet Diabetes & endocrinology. 2020 Mar 1;8(3):226-38.

Ilonen J, Lempainen J, Veijola R. The heterogeneous pathogenesis of type 1 diabetes mellitus. Nature Reviews Endocrinology. 2019 Nov;15(11):635-50. https://doi.org/10.1038/s41574-019-0254-y

Paschou SA, Papadopoulou-Marketou N, Chrousos GP, Kanaka-Gantenbein C. On type 1 diabetes mellitus pathogenesis. Endocrine connections. 2018 Jan 1;7(1):R38-46.

Chiou J, Geusz RJ, Okino ML, Han JY, Miller M, Melton R, Beebe E, Benaglio P, Huang S, Korgaonkar K, Heller S. Interpreting type 1 diabetes risk with genetics and single-cell epigenomics. Nature. 2021 Jun 17;594(7863):398-402. https://doi.org/10.1038/s41586-021-03552-w

Corbin KD, Driscoll KA, Pratley RE, Smith SR, Maahs DM, Mayer-Davis EJ, Advancing Care for Type 1 Diabetes and Obesity Network (ACT1ON). Obesity in type 1 diabetes: pathophysiology, clinical impact, and mechanisms. Endocrine reviews. 2018 Oct;39(5):629-63.

Redondo MJ, Geyer S, Steck AK, Sharp S, Wentworth JM, Weedon MN, Antinozzi P, Sosenko J, Atkinson M, Pugliese A, Oram RA. A type 1 diabetes genetic risk score predicts progression of islet autoimmunity and development of type 1 diabetes in individuals at risk. Diabetes care. 2018 Sep 1;41(9):1887-94.

Battaglia M, Ahmed S, Anderson MS, Atkinson MA, Becker D, Bingley PJ, Bosi E, Brusko TM, DiMeglio LA, Evans-Molina C, Gitelman SE. Introducing the endotype concept to address the challenge of disease heterogeneity in type 1 diabetes. Diabetes care. 2020 Jan 1;43(1):5-12.

Powers AC. Type 1 diabetes mellitus: much progress, many opportunities. The Journal of clinical investigation. 2021 Apr 15;131(8).

Goodwin G. Type 1 diabetes mellitus and celiac disease: distinct autoimmune disorders that share common pathogenic mechanisms. Hormone research in paediatrics. 2020 Apr 29;92(5):285-92.

Eizirik DL, Pasquali L, Cnop M. Pancreatic β-cells in type 1 and type 2 diabetes mellitus: different pathways to failure. Nature Reviews Endocrinology. 2020 Jul;16(7):349-62.

Zheng P, Li Z, Zhou Z. Gut microbiome in type 1 diabetes: A comprehensive review. Diabetes/metabolism research and reviews. 2018 Oct;34(7):e3043.

Roep BO, Thomaidou S, van Tienhoven R, Zaldumbide A. Type 1 diabetes mellitus as a disease of the β-cell (do not blame the immune system?). Nature Reviews Endocrinology. 2021 Mar;17(3):150-61.

Brissova M, Haliyur R, Saunders D, Shrestha S, Dai C, Blodgett DM, Bottino R, Campbell-Thompson M, Aramandla R, Poffenberger G, Lindner J. α cell function and gene expression are compromised in type 1 diabetes. Cell reports. 2018 Mar 6;22(10):2667-76.

Chiang JL, Maahs DM, Garvey KC, Hood KK, Laffel LM, Weinzimer SA, Wolfsdorf JI, Schatz D. Type 1 diabetes in children and adolescents: a position statement by the American Diabetes Association. Diabetes care. 2018 Sep;41(9):2026. doi: https://doi.org/10.2337/dci18-0023

Han H, Li Y, Fang J, Liu G, Yin J, Li T, Yin Y. Gut microbiota and type 1 diabetes. International journal of molecular sciences. 2018 Mar 27;19(4):995.

Warshauer JT, Bluestone JA, Anderson MS. New frontiers in the treatment of type 1 diabetes. Cell metabolism. 2020 Jan 7;31(1):46-61.

Forouhi NG, Wareham NJ. Epidemiology of diabetes. Medicine. 2019 Jan 1;47(1):22-7.

Aw W, Fukuda S. Understanding the role of the gut ecosystem in diabetes mellitus. Journal of diabetes investigation. 2018 Jan;9(1):5-12.

Holt RI, DeVries JH, Hess-Fischl A, Hirsch IB, Kirkman MS, Klupa T, Ludwig B, Nørgaard K, Pettus J, Renard E, Skyler JS. The management of type 1 diabetes in adults. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes care. 2021 Nov 1;44(11):2589-625. https://doi.org/10.2337/dci21-0043

Tan SY, Wong JL, Sim YJ, Wong SS, Elhassan SA, Tan SH, Lim GP, Tay NW, Annan NC, Bhattamisra SK, Candasamy M. Type 1 and 2 diabetes mellitus: A review on current treatment approach and gene therapy as potential intervention. Diabetes & metabolic syndrome: clinical research & reviews. 2019 Jan 1;13(1):364-72.

Chellappan DK, Sivam NS, Teoh KX, Leong WP, Fui TZ, Chooi K, Khoo N, Yi FJ, Chellian J, Cheng LL, Dahiya R. Gene therapy and type 1 diabetes mellitus. Biomedicine & Pharmacotherapy. 2018 Dec 1;108:1188-200.

Bhatwadekar AD, Shughoury A, Belamkar A, Ciulla TA. Genetics of diabetic retinopathy, a leading cause of irreversible blindness in the industrialized world. Genes. 2021 Jul 31;12(8):1200.

Weng J, Zhou Z, Guo L, Zhu D, Ji L, Luo X, Mu Y, Jia W. Incidence of type 1 diabetes in China, 2010-13: population based study. Bmj. 2018 Jan 4;360.

Atkinson MA, Roep BO, Posgai A, Wheeler DC, Peakman M. The challenge of modulating β-cell autoimmunity in type 1 diabetes. The Lancet Diabetes & Endocrinology. 2019 Jan 1;7(1):52-64.

Harsch IA, Konturek PC. The role of gut microbiota in obesity and type 2 and type 1 diabetes mellitus: new insights into “old” diseases. Medical sciences. 2018 Apr 17;6(2):32

Leiva-Gea I, Sánchez-Alcoholado L, Martín-Tejedor B, Castellano-Castillo D, Moreno-Indias I, Urda-Cardona A, Tinahones FJ, Fernández-García JC, Queipo-Ortuño MI. Gut microbiota differs in composition and functionality between children with type 1 diabetes and MODY2 and healthy control subjects: a case-control study. Diabetes care. 2018 Nov 1;41(11):2385-95.