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Anti-Glutamic Acid Decarboxylase-65 and Insulin Autoantibodies in Patients with Type 1 Diabetes Mellitus of Eastern Nepal
Corresponding Author(s) : Dr. Apeksha Niraula
Malaysian Journal of Clinical Biochemistry,
Vol. 2 No. 1 (2025): Young Scientists Award (34th MACB Conference 2024)
Abstract
Type 1 Diabetes Mellitus (T1DM) has been a rising trend in the younger population globally. There are limited data available on T1DM in the Nepalese population with negligible reports on the antibody status in the T1DM of the Nepalese population. This study aimed to estimate the autoantibodies namely glutamic acid decarboxylase-65 (GADA) and Insulin autoantibody (IAA) positivity and assess the serum vitamin D levels in Type 1 DM patients of eastern Nepal. A hospital-based cross-sectional study was conducted among 54 diagnosed cases of T1DM attending the B.P. Koirala Institute of Health Sciences (BPKIHS), Dharan, Nepal for one year (15th January- 15th December 2020). Convenient sampling was used to recruit the patients. Serum GADA and IAA were estimated using a chemiluminescence immunoassay (CLIA). Quantitative variables were expressed as a mean and standard deviation. The level of significance was established as p< 0.05. We recruited fifty-four patients (36 female and 18 male). The mean age of the patient was 22.44 ± 9.69 years. GADA positivity was present in 18.5% (n=10) of the patients and IAA was positive in 24.07% (n=13). Our study unveiled a lower prevalence of GADA and IAA in the Nepalese population compared to previous studies. In addition, we report female preponderance in patients with both GADA and IAA positivity.
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- 1. Alshiekh, S., Larsson, H. E., Ivarsson, S. A., & Lernmark, Å. (2017). Autoimmune type 1 diabetes. In R. I. G. Holt, C. S. Cockram, A. Flyvbjerg, & B. J. Goldstein (Eds.), Textbook of diabetes. Wiley Blackwell.
- 2. American Diabetes Association. (2017). American Diabetes Association Standards of medical care in diabetes–2017. Diabetes care, 40(Suppl. 1), S1.
- 3. American Diabetes Association. (2020). 2. Classification and diagnosis of diabetes: standards of medical care in diabetes—2020. Diabetes care, 43(Supplement_1), S14-S31.
- 4. Amutha, A., & Mohan, V. (2013). Childhood and adolescent onset type 1 diabetes in India. MGM Journal of Medical Sciences.
- 5. Baker II, P. R., & Eisenbarth, G. S. (2009). Type 1 diabetes—pathogenesis, prediction, and prevention. US Endocrinology, 05(01), 79. https://doi.org/10.17925/use.2009.05.1.79
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- 7. Basu, M., Pandit, K., Banerjee, M., Mondal, S. A., Mukhopadhyay, P., & Ghosh, S. (2020). Profile of auto-antibodies (disease-related and other) in children with type 1 diabetes. Indian Journal of Endocrinology and Metabolism, 24(3), 256-259.
- 8. Bronner, M. B., Peeters, M. A., Sattoe, J. N., & van Staa, A. (2020). The impact of type 1 diabetes on young adults’ health-related quality of life. Health and quality of life outcomes, 18, 1-7.
- 9. Cheng, B. W., Lo, F. S., Wang, A. M., Hung, C. M., Huang, C. Y., Ting, W. H., ... & Lee, Y. J. (2018). Autoantibodies against islet cell antigens in children with type 1 diabetes mellitus. Oncotarget, 9(23), 16275.
- 10. Dabelea, D., Pihoker, C., Talton, J. W., D’Agostino Jr, R. B., Fujimoto, W., Klingensmith, G. J., ... & SEARCH for Diabetes in Youth Study. (2011). Etiological approach to characterization of diabetes type: the SEARCH for Diabetes in Youth Study. Diabetes care, 34(7), 1628-1633.
- 11. Dayal, D., Samprati, M., Kaur, N., Minz, R. W., & Jayaraman, D. (2015). Prevalence of beta-cell, thyroid and celiac autoimmunity in North Indian children with recent-onset type 1 diabetes (T1D). Journal of Clinical and Diagnostic Research: JCDR, 9(3), SM01.
- 12. Dhanwal, D. K., Agarwal, S., Garg, S., & Agarwal, P. (2014). Clinical & immunological profile of newly diagnosed patients with youth onset diabetes mellitus. Indian Journal of Medical Research, 140(3), 356-360.
- 13. Endesfelder, D., Hagen, M., Winkler, C., Haupt, F., Zillmer, S., Knopff, A., ... & Achenbach, P. (2016). A novel approach for the analysis of longitudinal profiles reveals delayed progression to type 1 diabetes in a subgroup of multiple-islet-autoantibody-positive children. Diabetologia, 59, 2172-2180.
- 14. Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. (2003). Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes care, 26(suppl_1), s5-s20.
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- 16. Gale, E. (2002). A missing link in the hygiene hypothesis?. Diabetologia, 45, 588-594.
- 17. Kimpimaki, T., Kulmala, P., Savola, K., Kupila, A., Korhonen, S., Simell, T., ... & Knip, M. (2002). Natural history of β-cell autoimmunity in young children with increased genetic susceptibility to type 1 diabetes recruited from the general population. The Journal of Clinical Endocrinology & Metabolism, 87(10), 4572-4579.
- 18. Kumar, K. M. P. (2015). Incidence trends for childhood type 1 diabetes in India. Indian journal of endocrinology and metabolism, 19(Suppl 1), S34-S35.
- 19. Maahs, D. M., West, N. A., Lawrence, J. M., & Mayer-Davis, E. J. (2010). Epidemiology of type 1 diabetes. Endocrinology and Metabolism Clinics, 39(3), 481-497.
- 20. Marita, A. R., Rane, S., Mokal, R. A., Nair, S. R., & Irani, A. (2004). Autoantibodies against GAD65 and IA‐2 in recently diagnosed Type 1 diabetic children from Western India. Diabetic medicine, 21(8), 956-957.
- 21. Mayer-Davis, E. J., Dabelea, D., Crandell, J. L., Crume, T., D’Agostino Jr, R. B., Dolan, L., & The, N. (2013). Nutritional factors and preservation of C-peptide in youth with recently diagnosed type 1 diabetes: SEARCH Nutrition Ancillary Study. Diabetes Care, 36(7), 1842-1850
- 22. Naaraayan, S. A., Dhakshayani, R. V., & Chandramohan, R. (2021). Autoimmunity in south Indian children with recently diagnosed type 1 diabetes mellitus. Journal of Diabetology, 12(2), 182-185.
- 23. Paudel, U., Paudyal, B. P., Kansakar, P., & Shakya, M. (2021). Clinical characteristics and perspectives of children and youths with type 1 diabetes attending Patan Hospital, Nepal. Journal of Patan Academy of Health Sciences, 8(1), 113-120.
- 24. Sanyal, D. (2020). Current perspective on auto-antibodies in type 1 diabetes. Indian Journal of Endocrinology and Metabolism, 24(3), 233-234.
- 25. Sanyal, D., Batabyal, S. K., Maity, S., & Chatterjee, S. (2019). Changing profile of GAD and IA-2 antibody positivity in Indian children with recently diagnosed type 1 diabetes mellitus. Clinical Diabetology, 8(2), 116-120.
- 26. Sanyal, D., Majumder, A., Chaudhuri, S. R., & Chatterjee, S. (2017). Thyroid profile and autoantibodies in Type 1 diabetes subjects: A perspective from Eastern India. Indian Journal of Endocrinology and Metabolism, 21(1), 45-50.
- 27. Scottish Diabetes Survey Monitoring Group (2016) Scottish Diabetes Survey 2016. http://www.diabetesinscotland.org.uk/Publications/Scottish%20Diabetes%20Survey%202016.pdf.
- 28. Shakya, B., Shrestha, N., & Shrestha, S. R. (2020). An epidemiological study of diabetes mellitus in productive aged urban Nepalese of Makalbari area of Gokarneshwor Municipality. Nepal Medical College Journal, 22(3), 173-180.
- 29. Shrestha, S., Maurya, M., & Manandhar, K. D. (2021). An Investigation on the Detection of Human Leucocyte Antigen HLA Class I Loci (A, B, C) and Class II Loci (DR, DQ) Allele Frequency in Nepalese Population by Next Generation Sequencing. Journal of Applied Pharmaceutical Sciences and Research, 4(1), 1-6.
- 30. Sorgjerd, E. P. (2019). Type 1 diabetes-related autoantibodies in different forms of diabetes. Current diabetes reviews, 15(3), 199-204.
- 31. Tandon, N., Shtauvere‐Brameus, A., Hagopian, W. A., & Sanjeevi, C. B. (2002). Prevalence of ICA‐12 and other autoantibodies in north Indian patients with early‐onset diabetes. Annals of the New York Academy of Sciences, 958(1), 214-217.
- 32. Thomas, N. J., Jones, S. E., Weedon, M. N., Shields, B. M., Oram, R. A., & Hattersley, A. T. (2018). Frequency and phenotype of type 1 diabetes in the first six decades of life: a cross-sectional, genetically stratified survival analysis from UK Biobank. The lancet Diabetes & endocrinology, 6(2), 122-129.
- 33. Tina-quant Hemoglobin A1c Gen. 3 package insert. Roche Diagnostics. 2022.
- 34. Tuladhar, A., Shrestha, S., Raut, P. P., Bhandari, P., & Shrestha, P. (2013). HLA antigen distribution in renal transplant recipients and donors. Journal of Nepal Health Research Council.
- 35. Wenzlau, J. M., Juhl, K., Yu, L., Moua, O., Sarkar, S. A., Gottlieb, P., ... & Hutton, J. C. (2007). The cation efflux transporter ZnT8 (Slc30A8) is a major autoantigen in human type 1 diabetes. Proceedings of the National Academy of Sciences, 104(43), 17040-17045.
- 36. Wenzlau, J. M., Frisch, L. M., Hutton, J. C., Fain, P. R., & Davidson, H. W. (2015). Changes in zinc transporter 8 autoantibodies following type 1 diabetes onset: the type 1 diabetes genetics consortium autoantibody workshop. Diabetes Care, 38(Supplement_2), S14-S20.
- 37. Wenzlau, J. M., Walter, M., Gardner, T. J., Frisch, L. M., Yu, L., Eisenbarth, G. S., ... & Hutton, J. C. (2010). Kinetics of the post-onset decline in zinc transporter 8 autoantibodies in type 1 diabetic human subjects. The Journal of Clinical Endocrinology & Metabolism, 95(10), 4712-4719.
- 38. WHO. (2023)10 facts on Diabetes. Available from: https://www.who.int/features/
- 39. Williams, C. L., Aitken, R. J., Wilson, I. V., Mortimer, G. L., Long, A. E., Williams, A. J., ... & Gillespie, K. M. (2022). The measurement of autoantibodies to insulin informs the diagnosis of diabetes in a childhood population negative for other autoantibodies. Diabetic Medicine, 39(12), e14979.
- 40. Zamanfar, D., Aarabi, M., Amini, M., & Monajati, M. (2020). Prevalence of autoantibodies in type 1 diabetes mellitus pediatrics in Mazandaran, North of Iran. Journal of Pediatric Endocrinology and Metabolism, 33(10), 1299-1305.
- 41. Zhang, M., Wang, X., Wang, R., Shu, J., Zhi, X., Gu, C., ... & Lv, L. (2022). Clinical study of autoantibodies in type 1 diabetes mellitus children with ketoacidosis or microalbuminuria. Journal of Clinical Laboratory Analysis, 36(1), e24164.
References
1. Alshiekh, S., Larsson, H. E., Ivarsson, S. A., & Lernmark, Å. (2017). Autoimmune type 1 diabetes. In R. I. G. Holt, C. S. Cockram, A. Flyvbjerg, & B. J. Goldstein (Eds.), Textbook of diabetes. Wiley Blackwell.
2. American Diabetes Association. (2017). American Diabetes Association Standards of medical care in diabetes–2017. Diabetes care, 40(Suppl. 1), S1.
3. American Diabetes Association. (2020). 2. Classification and diagnosis of diabetes: standards of medical care in diabetes—2020. Diabetes care, 43(Supplement_1), S14-S31.
4. Amutha, A., & Mohan, V. (2013). Childhood and adolescent onset type 1 diabetes in India. MGM Journal of Medical Sciences.
5. Baker II, P. R., & Eisenbarth, G. S. (2009). Type 1 diabetes—pathogenesis, prediction, and prevention. US Endocrinology, 05(01), 79. https://doi.org/10.17925/use.2009.05.1.79
6. Balasubramanian, K., Dabadghao, P., Bhatia, V., Colman, P. G., Gellert, S. A., Bharadwaj, U., ... & Bhatia, E. (2003). High frequency of type 1B (idiopathic) diabetes in North Indian children with recent-onset diabetes. Diabetes Care, 26(9), 2697-2697.
7. Basu, M., Pandit, K., Banerjee, M., Mondal, S. A., Mukhopadhyay, P., & Ghosh, S. (2020). Profile of auto-antibodies (disease-related and other) in children with type 1 diabetes. Indian Journal of Endocrinology and Metabolism, 24(3), 256-259.
8. Bronner, M. B., Peeters, M. A., Sattoe, J. N., & van Staa, A. (2020). The impact of type 1 diabetes on young adults’ health-related quality of life. Health and quality of life outcomes, 18, 1-7.
9. Cheng, B. W., Lo, F. S., Wang, A. M., Hung, C. M., Huang, C. Y., Ting, W. H., ... & Lee, Y. J. (2018). Autoantibodies against islet cell antigens in children with type 1 diabetes mellitus. Oncotarget, 9(23), 16275.
10. Dabelea, D., Pihoker, C., Talton, J. W., D’Agostino Jr, R. B., Fujimoto, W., Klingensmith, G. J., ... & SEARCH for Diabetes in Youth Study. (2011). Etiological approach to characterization of diabetes type: the SEARCH for Diabetes in Youth Study. Diabetes care, 34(7), 1628-1633.
11. Dayal, D., Samprati, M., Kaur, N., Minz, R. W., & Jayaraman, D. (2015). Prevalence of beta-cell, thyroid and celiac autoimmunity in North Indian children with recent-onset type 1 diabetes (T1D). Journal of Clinical and Diagnostic Research: JCDR, 9(3), SM01.
12. Dhanwal, D. K., Agarwal, S., Garg, S., & Agarwal, P. (2014). Clinical & immunological profile of newly diagnosed patients with youth onset diabetes mellitus. Indian Journal of Medical Research, 140(3), 356-360.
13. Endesfelder, D., Hagen, M., Winkler, C., Haupt, F., Zillmer, S., Knopff, A., ... & Achenbach, P. (2016). A novel approach for the analysis of longitudinal profiles reveals delayed progression to type 1 diabetes in a subgroup of multiple-islet-autoantibody-positive children. Diabetologia, 59, 2172-2180.
14. Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. (2003). Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes care, 26(suppl_1), s5-s20.
15. Goncalves, C. B. C. D., Silva, I. N., Tanure, M. G., & Bahia, M. (2013). Study of prevalence of celiac disease in children with type 1 diabetes mellitus: result of 10 years of follow-up. Arquivos Brasileiros de Endocrinologia & Metabologia, 57, 375-380.
16. Gale, E. (2002). A missing link in the hygiene hypothesis?. Diabetologia, 45, 588-594.
17. Kimpimaki, T., Kulmala, P., Savola, K., Kupila, A., Korhonen, S., Simell, T., ... & Knip, M. (2002). Natural history of β-cell autoimmunity in young children with increased genetic susceptibility to type 1 diabetes recruited from the general population. The Journal of Clinical Endocrinology & Metabolism, 87(10), 4572-4579.
18. Kumar, K. M. P. (2015). Incidence trends for childhood type 1 diabetes in India. Indian journal of endocrinology and metabolism, 19(Suppl 1), S34-S35.
19. Maahs, D. M., West, N. A., Lawrence, J. M., & Mayer-Davis, E. J. (2010). Epidemiology of type 1 diabetes. Endocrinology and Metabolism Clinics, 39(3), 481-497.
20. Marita, A. R., Rane, S., Mokal, R. A., Nair, S. R., & Irani, A. (2004). Autoantibodies against GAD65 and IA‐2 in recently diagnosed Type 1 diabetic children from Western India. Diabetic medicine, 21(8), 956-957.
21. Mayer-Davis, E. J., Dabelea, D., Crandell, J. L., Crume, T., D’Agostino Jr, R. B., Dolan, L., & The, N. (2013). Nutritional factors and preservation of C-peptide in youth with recently diagnosed type 1 diabetes: SEARCH Nutrition Ancillary Study. Diabetes Care, 36(7), 1842-1850
22. Naaraayan, S. A., Dhakshayani, R. V., & Chandramohan, R. (2021). Autoimmunity in south Indian children with recently diagnosed type 1 diabetes mellitus. Journal of Diabetology, 12(2), 182-185.
23. Paudel, U., Paudyal, B. P., Kansakar, P., & Shakya, M. (2021). Clinical characteristics and perspectives of children and youths with type 1 diabetes attending Patan Hospital, Nepal. Journal of Patan Academy of Health Sciences, 8(1), 113-120.
24. Sanyal, D. (2020). Current perspective on auto-antibodies in type 1 diabetes. Indian Journal of Endocrinology and Metabolism, 24(3), 233-234.
25. Sanyal, D., Batabyal, S. K., Maity, S., & Chatterjee, S. (2019). Changing profile of GAD and IA-2 antibody positivity in Indian children with recently diagnosed type 1 diabetes mellitus. Clinical Diabetology, 8(2), 116-120.
26. Sanyal, D., Majumder, A., Chaudhuri, S. R., & Chatterjee, S. (2017). Thyroid profile and autoantibodies in Type 1 diabetes subjects: A perspective from Eastern India. Indian Journal of Endocrinology and Metabolism, 21(1), 45-50.
27. Scottish Diabetes Survey Monitoring Group (2016) Scottish Diabetes Survey 2016. http://www.diabetesinscotland.org.uk/Publications/Scottish%20Diabetes%20Survey%202016.pdf.
28. Shakya, B., Shrestha, N., & Shrestha, S. R. (2020). An epidemiological study of diabetes mellitus in productive aged urban Nepalese of Makalbari area of Gokarneshwor Municipality. Nepal Medical College Journal, 22(3), 173-180.
29. Shrestha, S., Maurya, M., & Manandhar, K. D. (2021). An Investigation on the Detection of Human Leucocyte Antigen HLA Class I Loci (A, B, C) and Class II Loci (DR, DQ) Allele Frequency in Nepalese Population by Next Generation Sequencing. Journal of Applied Pharmaceutical Sciences and Research, 4(1), 1-6.
30. Sorgjerd, E. P. (2019). Type 1 diabetes-related autoantibodies in different forms of diabetes. Current diabetes reviews, 15(3), 199-204.
31. Tandon, N., Shtauvere‐Brameus, A., Hagopian, W. A., & Sanjeevi, C. B. (2002). Prevalence of ICA‐12 and other autoantibodies in north Indian patients with early‐onset diabetes. Annals of the New York Academy of Sciences, 958(1), 214-217.
32. Thomas, N. J., Jones, S. E., Weedon, M. N., Shields, B. M., Oram, R. A., & Hattersley, A. T. (2018). Frequency and phenotype of type 1 diabetes in the first six decades of life: a cross-sectional, genetically stratified survival analysis from UK Biobank. The lancet Diabetes & endocrinology, 6(2), 122-129.
33. Tina-quant Hemoglobin A1c Gen. 3 package insert. Roche Diagnostics. 2022.
34. Tuladhar, A., Shrestha, S., Raut, P. P., Bhandari, P., & Shrestha, P. (2013). HLA antigen distribution in renal transplant recipients and donors. Journal of Nepal Health Research Council.
35. Wenzlau, J. M., Juhl, K., Yu, L., Moua, O., Sarkar, S. A., Gottlieb, P., ... & Hutton, J. C. (2007). The cation efflux transporter ZnT8 (Slc30A8) is a major autoantigen in human type 1 diabetes. Proceedings of the National Academy of Sciences, 104(43), 17040-17045.
36. Wenzlau, J. M., Frisch, L. M., Hutton, J. C., Fain, P. R., & Davidson, H. W. (2015). Changes in zinc transporter 8 autoantibodies following type 1 diabetes onset: the type 1 diabetes genetics consortium autoantibody workshop. Diabetes Care, 38(Supplement_2), S14-S20.
37. Wenzlau, J. M., Walter, M., Gardner, T. J., Frisch, L. M., Yu, L., Eisenbarth, G. S., ... & Hutton, J. C. (2010). Kinetics of the post-onset decline in zinc transporter 8 autoantibodies in type 1 diabetic human subjects. The Journal of Clinical Endocrinology & Metabolism, 95(10), 4712-4719.
38. WHO. (2023)10 facts on Diabetes. Available from: https://www.who.int/features/
39. Williams, C. L., Aitken, R. J., Wilson, I. V., Mortimer, G. L., Long, A. E., Williams, A. J., ... & Gillespie, K. M. (2022). The measurement of autoantibodies to insulin informs the diagnosis of diabetes in a childhood population negative for other autoantibodies. Diabetic Medicine, 39(12), e14979.
40. Zamanfar, D., Aarabi, M., Amini, M., & Monajati, M. (2020). Prevalence of autoantibodies in type 1 diabetes mellitus pediatrics in Mazandaran, North of Iran. Journal of Pediatric Endocrinology and Metabolism, 33(10), 1299-1305.
41. Zhang, M., Wang, X., Wang, R., Shu, J., Zhi, X., Gu, C., ... & Lv, L. (2022). Clinical study of autoantibodies in type 1 diabetes mellitus children with ketoacidosis or microalbuminuria. Journal of Clinical Laboratory Analysis, 36(1), e24164.