Characterisation of islet antibody-negative type 1 diabetes mellitus in Indian children. - National Genomics Data Center (CNCB-NGDC)

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Characterisation of islet antibody-negative type 1 diabetes mellitus in Indian children.

Jayakrishnan C Menon, Pratibha Singh, Archana Archana, Uma Kanga, Preeti Singh, Medha Mittal, Atul Garg, Anju Seth, Vijayalakshmi Bhatia, Preeti Dabadghao, Siddhnath Sudhanshu, Ruchira Vishwakarma, Shivendra Verma, S K Singh, Eesh Bhatia

Author Information

Jayakrishnan C Menon: Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.
Pratibha Singh: Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.
Archana Archana: Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.
Uma Kanga: Department of Immunogenetics and Transplant Immunology, All India Institute of Medical Sciences, New Delhi, India.
Preeti Singh: Department of Paediatrics, Lady Hardinge Medical College, New Delhi, India.
Medha Mittal: Department of Paediatrics, Chacha Nehru Bal Chikitsalay, New Delhi, India.
Atul Garg: Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.
Anju Seth: Department of Paediatrics, Lady Hardinge Medical College, New Delhi, India.
Vijayalakshmi Bhatia: Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India. ORCID
Preeti Dabadghao: Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.
Siddhnath Sudhanshu: Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.
Ruchira Vishwakarma: Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.
Shivendra Verma: Department of Endocrinology, GSVM Medical College, Kanpur, Uttar Pradesh, India.
S K Singh: Department of Endocrinology, Banaras Hindu University, Varanasi, Uttar Pradesh, India.
Eesh Bhatia: Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India. ORCID

PMID: 39556519 DOI: 10.1111/dme.15477

AIMS: Islet antibody-negative type 1 diabetes mellitus (T1DM) has not been well characterised. We determined the frequency of antibody-negative T1DM and compared it with antibody-positive T1DM in a cohort of north Indian children.
METHODS: In a multi-centre, prospective, observational study, 176 Indian children (age 1-18 years) were assessed within 2 weeks of diagnosis of T1DM. Antibodies against GAD65 (GADA), islet antigen-2 (IA-2A) and zinc transporter 8 (ZnT8A), were estimated using validated ELISA. HLA-DRB1, DQA1 and DQB1 alleles were studied by Luminex-based typing. Monogenic diabetes was determined by targeted next-generation sequencing using the Illumina platform.
RESULTS: After excluding 12 children with monogenic diabetes, GADA, IA-2A and ZnT8A were present in 124 (76%), 60 (37%) and 62 (38%) o children, respectively, while 24 (15%) were negative for all antibodies. A single antibody (most frequently GADA) was present in 68 (41%) of children, while all three antibodies were found in 34 (21%). Islet antibody-negative T1DM (n = 24, 15%) did not differ from antibody-positive children in their clinical features, HbA1c or plasma C-peptide, both at onset or after 1 year follow-up (available in 62 children). The frequency of other organ-specific antibodies or high-risk HLA-DR and DQ alleles were also similar. Children with a single islet antibody did not differ from those with multiple antibodies.
CONCLUSIONS: The frequency of various islet-antibodies, in isolation and combination, differed considerably from studies among children of European descent with T1DM. Children with T1DM who were islet antibody-negative were indistinguishable from those who were antibody-positive.

human leucocyte antigen idiopathic type 1 diabetes islet‐antibody type 1 diabetes mellitus type 1B diabetes

Powers AC. Type 1 diabetes mellitus: much progress, many opportunities. J Clin Invest. 2021;131(8):e142242.
American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2014;37(Suppl 1):S81‐S90.
Bingley PJ. Clinical applications of diabetes antibody testing. J Clin Endocrinol Metab. 2010;95(1):25‐33.
Andersson C, Vaziri‐Sani F, Delli A, et al. Triple specificity of ZnT8 autoantibodies in relation to HLA and other islet autoantibodies in childhood and adolescent type 1 diabetes. Pediatr Diabetes. 2013;14(2):97‐105.
Dabelea D, Pihoker C, Talton JW, et al. Etiological approach to characterization of diabetes type: the SEARCH for diabetes in youth study. Diabetes Care. 2011;34(7):1628‐1633.
Harsunen M, Kettunen JLT, Härkönen T, et al. Identification of monogenic variants in more than ten per cent of children without type 1 diabetes‐related autoantibodies at diagnosis in the Finnish pediatric diabetes register. Diabetologia. 2023;66(3):438‐449.
Chen Y, Xie Y, Xia Y, et al. Prevalence, clinical characteristics and HLA genotypes of idiopathic type 1 diabetes: a cross‐sectional study. Diabetes Metab Res Rev. 2023;39(6):e3676.
Vipin VP, Zaidi G, Watson K, et al. High prevalence of idiopathic (islet antibody‐negative) type 1 diabetes among Indian children and adolescents. Pediatr Diabetes. 2021;22(1):47‐51, published correction appears in Pediatr diabetes. 2022 Jun;23(4):527. doi:10.1111/pedi.13332
Imagawa A, Hanafusa T. Pathogenesis of fulminant type 1 diabetes. Rev Diabet Stud. 2006;3(4):169‐177.
Choukem SP, Sobngwi E, Boudou P, et al. β‐ and α‐cell dysfunctions in Africans with ketosis‐prone atypical diabetes during near‐normoglycemic remission. Diabetes Care. 2013;36(1):118‐123.
Ushijima K, Fukami M, Ayabe T, et al. Comprehensive screening for monogenic diabetes in 89 Japanese children with insulin‐requiring antibody‐negative type 1 diabetes. Pediatr Diabetes. 2018;19(2):243‐250.
Urrutia I, Martínez R, Rica I, et al. Negative autoimmunity in a Spanish pediatric cohort suspected of type 1 diabetes, could it be monogenic diabetes? PLoS One. 2019;14(7):e0220634.
Abdel‐Karim T, Haris B, Afyouni H, et al. The epidemiology and genetic analysis of children with idiopathic type 1 diabetes in the State of Qatar. J Endocr Soc. 2021;5(10):bvab131.
Hameed S, Ellard S, Woodhead HJ, et al. Persistently autoantibody negative (PAN) type 1 diabetes mellitus in children. Pediatr Diabetes. 2011;12(3 Pt 1):142‐149.
Thomas NJ, Walkey HC, Kaur A, et al. The relationship between islet autoantibody status and the genetic risk of type 1 diabetes in adult‐onset type 1 diabetes. Diabetologia. 2023;66(2):310‐320.
Shivaprasad C, Mittal R, Dharmalingam M, Kumar PK. Zinc transporter‐8 autoantibodies can replace IA‐2 autoantibodies as a serological marker for juvenile onset type 1 diabetes in India. Indian J Endocr Metab. 2014;18(3):345‐349.
Kelly MA, Alvi NS, Croft NJ, Mijovic CH, Bottazzo GF, Barnett AH. Genetic and immunological characteristics of type I diabetes mellitus in an indo‐Aryan population. Diabetologia. 2000;43(4):450‐456.
Menon JC, Singh P, Archana A, et al. High frequency of recessive WFS1 mutations among Indian children with islet antibody‐negative type 1 diabetes. J Clin Endocrinol Metab. 2024;109(3):e1072‐e1082.
Indian Academy of Pediatrics Growth Charts Committee, Khadilkar V, Yadav S, et al. Revised IAP growth charts for height, weight and body mass index for 5‐ to 18‐year‐old Indian children. Indian Pediatr. 2015;52(1):47‐55.
WHO. AnthroPlus for personal computers manual: software for assessing growth of the world's children and adolescents. WHO. 2009 https://cdn.who.int/media/docs/default‐source/child‐growth/growth‐reference‐5‐19‐years/who‐anthroplus‐manual.pdf
Lampasona V, Pittman DL, Williams AJ, et al. Islet autoantibody standardization program 2018 workshop: Interlaboratory comparison of glutamic acid decarboxylase autoantibody assay performance. Clin Chem. 2019;65(9):1141‐1152.
Kumar N, Mehra NK, Kanga U, et al. Diverse human leukocyte antigen association of type 1 diabetes in north India. J Diabetes. 2019;11(9):719‐728.
Redondo MJ, Sosenko J, Libman I, et al. Single islet autoantibody at diagnosis of clinical type 1 diabetes is associated with older age and insulin resistance. J Clin Endocrinol Metab. 2020;105(5):1629‐1640.
Williams CL, Aitken RJ, Wilson IV, et al. The measurement of autoantibodies to insulin informs diagnosis of diabetes in a childhood population negative for other autoantibodies. Diabet Med. 2022;39(12):e14979.
Maziarz M, Hagopian W, Palmer JP, et al. Non‐HLA type 1 diabetes genes modulate disease risk together with HLA‐DQ and islet autoantibodies. Genes Immun. 2015;16(8):541‐551.
Mikk ML, Pfeiffer S, Kiviniemi M, et al. HLA‐DR‐DQ haplotypes and specificity of the initial autoantibody in islet specific autoimmunity. Pediatr Diabetes. 2020;21(7):1218‐1226.
Juusola M, Parkkola A, Härkönen T, et al. Positivity for zinc transporter 8 autoantibodies at diagnosis is subsequently associated with reduced β‐cell function and higher exogenous insulin requirement in children and adolescents with type 1 diabetes. Diabetes Care. 2016;39(1):118‐121.
Nieto J, Castillo B, Astudillo M, et al. Islet autoantibody types mark differential clinical characteristics at diagnosis of pediatric type 1 diabetes. Pediatr Diabetes. 2021;22(6):882‐888.
Tiberti C, Buzzetti R, Anastasi E, et al. Autoantibody negative new onset type 1 diabetic patients lacking high risk HLA alleles in a Caucasian population: are these type 1b diabetes cases? Diabetes Metab Res Rev. 2000;16(1):8‐14.
McLaughlin KA, Richardson CC, Ravishankar A, et al. Identification of Tetraspanin‐7 as a target of autoantibodies in type 1 diabetes. Diabetes. 2016;65(6):1690‐1698.

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