Islet Autoantibody and Beta Cell Secretory Status at Diagnosis in Young Bangladeshi with Phenotypically Type 2 Diabetes
DOI:
https://doi.org/10.15605/jafes.041.01.5033Keywords:
young diabetes, phenotypic T2DM, iselt autoantibodies, C-peptideAbstract
Background. The overlapping clinical features in young-onset type 2 diabetes (T2DM) present significant diagnostic difficulties. Variable autoimmunity and beta-cell dysfunction related to this phenomenon are not sufficiently consolidated to distinguish subclasses.
Objectives. To determine the frequency of islet autoantibodies and beta-cell secretory status in phenotypically young Bangladeshis with T2DM.
Methodology. This cross-sectional study enrolled 83 patients with newly diagnosed young-onset phenotypically T2DM, aged 10 to 29 years, comprising 34 males (41%) and 48 females (59%), using non-probability purposive sampling. The demographic and clinical features of the patients were recorded. A fasting blood sample was collected for C-peptide and islet antibodies (anti-glutamic acid decarboxylase [GAD], zinc transporter 8 [ZnT8], and islet antigen 2 [IA-2] antibodies). C-peptide, anti-GAD Ab, and IA-2 Ab were measured by chemiluminescence, while ZnT8 Ab was measured by enzyme-linked immunosorbent assay (ELISA).
Results. An adequate beta-cell secretory reserve was present in 97.6% of participants (n = 82), with a median C-peptide level of 4.3 ng/mL (IQR: 3.0–6.7). Of the 82 patients included, GAD Ab was found to be positive in 17% (n = 14), ZnT8 Ab in 2.4% (n = 2), and none were positive for IA-2 Ab or a double antibody (ZnT8 Ab + GAD Ab). The frequency of double diabetes (DD) [GAD Ab positive subjects] was 17% (14/82). Comparing the GAD Ab-positive and negative groups, the former had a significantly lower homeostasis model assessment of β-cell function (HOMA-B) at 24.7 (16.3–99.1) versus 81.9 (30–154) in the latter (p = 0.02), and a significantly higher fasting plasma glucose (FPG) median IQR at 16 mmol/L (10–19) compared to 9.5 (6.7–14.5) (p = 0.04) in the negative group. The body mass index (BMI) was the only significant predictor of C-peptide (β = 0.44, p < 0.001).
Conclusion. GAD Ab was the most commonly detectable antibody in this study of young-onset phenotypically T2DM patients. The concentration of GAD Ab may influence the phenotypic presentation, but it is not a predictor of C-peptide levels. Beta-cell dysfunction in this subset of patients may depend on certain yet unexplored factors.
Downloads
References
Afroz A, Alam K, Ali L, et al. Type 2 diabetes mellitus in Bangladesh: A prevalence based cost-of-illness study. BMC Health Serv Res. 2019;19:601. https://pubmed.ncbi.nlm.nih.gov/31455307 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6712789 https://doi.org/10.1186/s12913-019-4440-3
Saeedi P, Petersohn I, Salpea P, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation diabetes atlas, 9th edition. Diabetes Res Clin Pract. 2019;157:107843. https://pubmed.ncbi.nlm.nih.gov/31518657 https://doi.org/10.1016/j.diabres.2019.107843
Gupta M, Singh N, Verma S. South Asians and cardiovascular risk: What clinicians should know. Circulation. 2006;113(25):e924-9. https://pubmed.ncbi.nlm.nih.gov/16801466 https://doi.org/10.1161/CIRCULATIONAHA.105.583815
Akhtar S, Nasir JA, Sarwar A, et al. Prevalence of diabetes and prediabetes in Bangladesh: A systematic review and meta-analysis. BMJ Open. 2020;10:e036086. https://pubmed.ncbi.nlm.nih.gov/32907898 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7482481 https://doi.org/10.1136/bmjopen-2019-036086
Skyler JS, Bakris GL, Bonifacio E, et al. Differentiation of diabetes by pathophysiology, natural history, and prognosis. Diabetes. 2017;66(2):241-55. https://pubmed.ncbi.nlm.nih.gov/27980006 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5384660 https://doi.org/10.2337/db16-0806
Goel A, Chiu H, Felton J, et al. T-cell responses to islet antigens improves detection of autoimmune diabetes and identifies patients with more severe beta-cell lesions in phenotypic type 2 diabetes. Diabetes. 2007;56(8):2110-5. https://pubmed.ncbi.nlm.nih.gov/17473222 https://doi.org/10.2337/db06-0552
Brooks-Worrell B, Narla R, Palmer JP. Islet autoimmunity in phenotypic type 2 diabetes patients. Diabetes Obes Metab. 2013;15 Suppl 3(03):137-40. https://pubmed.ncbi.nlm.nih.gov/24003930 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260534 https://doi.org/10.1111/dom.12167
Hathout EH, Thomas W, El-Shahawy M, et al. Diabetic autoimmune markers in children and adolescents with type 2 diabetes. Pediatrics. 2001;107(6):e102. https://pubmed.ncbi.nlm.nih.gov/11389300 https://doi.org/10.1542/peds.107.6.e102
Mottalib A, Kasetty M, Mar JY, et al. Weight management in patients with type 1 diabetes and obesity. Curr Diab Rep. 2017;17:92. https://pubmed.ncbi.nlm.nih.gov/28836234 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5569154 https://doi.org/10.1007/s11892-017-0918-8
Khawandanah J. Double or hybrid diabetes: A systematic review on disease prevalence, characteristics and risk factors. Nutr Diabetes. 2019;9:33. https://pubmed.ncbi.nlm.nih.gov/31685799 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6828774 https://doi.org/10.1038/s41387-019-0101-1
Chillarón JJ, Flores-Le-Roux JA, Goday A, et al. Metabolic syndrome and type-1 diabetes mellitus: Prevalence and associated factors. Rev Esp Cardiol. 2010;63(4):423-9. https://pubmed.ncbi.nlm.nih.gov/20334808
Brooks-Worrell BM, Greenbaum CJ, Palmer JP, et al. Autoimmunity to islet proteins in children diagnosed with new-onset diabetes. J Clin Endocrinol Metab. 2004;89(5):2222-7. https://pubmed.ncbi.nlm.nih.gov/15126545 https://doi.org/10.1210/jc.2003-031360
Rahman ME, Islam MS, Bishwas MS, et al. Physical inactivity and sedentary behaviors in the Bangladeshi population during the COVID-19 pandemic: An online cross-sectional survey. Heliyon. 2020;6:e05392. https://pubmed.ncbi.nlm.nih.gov/33163666 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598079 https://doi.org/10.1016/j.heliyon.2020.e05392
Kuczmarski RJ, Ogden CL, Guo SS, et al. 2000 CDC growth charts for the United States: Methods and development. Vital Health Stat 11. 2002;(246):1-190. https://pubmed.ncbi.nlm.nih.gov/12043359
Misra A, Vikram NK, Gupta R, et al. Waist circumference cutoff points and action levels for Asian Indians for identification of abdominal obesity. Int J Obes (Lond). 2006;30(1):106-11. https://pubmed.ncbi.nlm.nih.gov/16189502 https://doi.org/10.1038/sj.ijo.0803111
Li X, Zhou ZG, Qi HY, et al. Replacement of insulin by fasting C-peptide in modified homeostasis model assessment to evaluate insulin resistance and islet beta cell function. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2004;29(4):419-23. https://pubmed.ncbi.nlm.nih.gov/16134594
Williams KV, Erbey JR, Becker D, et al. Can clinical factors estimate insulin resistance in type 1 diabetes? Diabetes. 2000;49(4):626-32. https://pubmed.ncbi.nlm.nih.gov/10871201 https://doi.org/10.2337/diabetes.49.4.626
Tosur M, Geyer SM, Rodriguez H, et al. Ethnic differences in progression of islet autoimmunity and type 1 diabetes in relatives at risk. Diabetologia. 2018;61(9):2043-53. https://pubmed.ncbi.nlm.nih.gov/29931415 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6611550 https://doi.org/10.1007/s00125-018-4660-9
Zinman B, Kahn SE, Haffner SM, et al. Phenotypic characteristics of GAD antibody-positive recently diagnosed patients with type 2 diabetes in North America and Europe. Diabetes. 2004;53(12):3193-200. https://pubmed.ncbi.nlm.nih.gov/15561950 https://doi.org/10.2337/diabetes.53.12.3193
Wenzlau JM, Juhl K, Yu L, et al. The cation efflux transporter ZnT8 (Slc30A8) is a major autoantigen in human type 1 diabetes. Proc Natl Acad Sci U S A. 2007;104(43):17040-5. https://pubmed.ncbi.nlm.nih.gov/17942684 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2040407 https://doi.org/10.1073/pnas.0705894104
Mishra BK, Shukla P, Aslam M, et al. Prevalence of double diabetes in youth onset diabetes patients from east Delhi and neighboring NCR region. Diabetes Metab Syndr. 2018;12(6):839-42. https://pubmed.ncbi.nlm.nih.gov/28899639 https://doi.org/10.1016/j.dsx.2017.08.016
Hwangbo Y, Kim JT, Kim EK, et al. Prevalence and clinical characteristics of recently diagnosed type 2 diabetes patients with positive anti-glutamic acid decarboxylase antibody. Diabetes Metab J. 2012;36(2):136-43. https://pubmed.ncbi.nlm.nih.gov/22540050 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3335895 https://doi.org/10.4093/dmj.2012.36.2.136
Tfayli H, Bacha F, Gungor N, et al. Phenotypic type 2 diabetes in obese youth: insulin sensitivity and secretion in islet cell antibody-negative versus -positive patients. Diabetes. 2009;58(3):738-44. https://pubmed.ncbi.nlm.nih.gov/19073767 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2646074 https://doi.org/10.2337/db08-1372
Hosen M, Sultana N, Hasan M, et al. Fasting serum C-peptide level may not be low in young-onset diabetes. J Diabetol. 2022;13(3):249-54.
Cho YM. Characteristics of the pathophysiology of type 2 diabetes in Asians. J Diabetes Investig. 2017;2(2):1-7. https://doi.org/10.21037/ales.2017.01.03
Zou X, Zhou X, Ji L, et al. The characteristics of newly diagnosed adult early-onset diabetes: A population-based cross-sectional study. Sci Rep. 2017;7:46534. https://pubmed.ncbi.nlm.nih.gov/28422176 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5396191 https://doi.org/10.1038/srep46534
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 Kishore Kumar Shil, Mashfiqul Hasan, Nusrat Sultana; Sayad Bin Abdus-Salam, Hafsa Mahrukh; Tahmina Ferdousi, Muhammed Abul Hasanat
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
The full license text is available at: http://creativecommons.org/licenses/by-nc/3.0/legalcode.
To request permission to translate, reproduce, download, or use articles or images for commercial reuse or business purposes from the Journal of the ASEAN Federation of Endocrine Societies (JAFES), kindly complete the Permission Request for Use of Copyrighted Material Form and email jafes@asia.com or jafes.editor@gmail.com.
A written agreement will be issued to the requester once permission has been granted.
