Cited by 20Diabetes and associated disordersDiabetes Management and ResearchGenetic Associations and Epidemiology

Clinical features, biochemistry and HLA-DRB1 status in youth-onset type 1 diabetes in Pakistan

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Fawwad, Asher, Govender, Denira, Ahmedani, Mohammad Yakoob, Basit, Abdul, Lane, Julie Ann, Mack, Steven John, Atkinson, Mark Alvin, Henry Wasserfall, Clive +2 more·2019·Diabetes Research and Clinical Practice

Abstract

Published information on diabetes in Pakistani youth is limited. We aimed to investigate the demographic, clinical, and biochemical features, and HLA-DRB1 alleles in new cases of diabetes affecting children and adolescents <22 years of age. The study was conducted at Baqai Institute of Diabetology and Endocrinology in Karachi from June 2013-December 2015. One hundred subjects aged <22 years at diagnosis were enrolled. Demographic characteristics, clinical information, biochemical parameters (blood glucose, HbA1c, C-peptide, glutamic acid decarboxylase 65 (GAD65) and islet antigen 2 (IA-2) autoantibodies) were measured. DNA from 100 subjects and 200 controls was extracted and genotyped for HLA-DRB1 using high-resolution genotyping technology. Ninety-nine subjects were clinically diagnosed as type 1 diabetes (T1D) and one as type 2 diabetes (T2D). Of the 99 with T1D, 57 (57.6%) were males and 42 (42.4%) females, with mean age at diagnosis 11.0 ± 5.2 years (range 1.6-21.7 years) and peaks at six and fifteen years. Fifty-seven subjects were assessed within one month of diagnosis and all within eleven months. For the subjects diagnosed as T1D, mean C-peptide was 0.63 ± 0.51 nmol/L (1.91 ± 1.53 ng/mL), with 16 (16.2%) IA2 positive, 53 (53.5%) GAD-65 positive, and 10 (10.1%) positive for both autoantibodies. In T1D patients, the allele DRB1*03:01 demonstrated highly significant T1D association (p < 10-16), with no apparent risk conferred by DRB1*04:xx alleles. CONCLUSIONS: Heterogeneous forms of T1D appear more common in children and youth in Pakistan than in European populations. Individual understanding of such cases could enable improved management strategies and healthier outcomes.

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  • C-peptide measurements and other advanced diagnostics and phenotyping are being implemented in youth in less advantaged regions who have been newly diagnosed with diabetes mellitus.

    “However, this picture is changing with C-peptide measurements and other advanced diagnostics and phenotyping being implemented in youth in less advantaged regions who have been newly diagnosed with diabetes mellitus93–98.”

    From The epidemiology of type 1 diabetes mellitus in older adults (2025) · cites this paper as [96]

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  1. [1]Craig ME, Jefferies C, Dabelea D, Balde N, Seth A, Donaghue KC. Definition, epidemiology, and classification of diabetes in children and adolescents. Pediatric Diabetes 2014: 15 (Suppl. 20): 4– 17. 25182305
  2. [2]DIAMOND Project Group. Incidence and trends of childhood type 1 diabetes worldwide 1990–1999. Diabet Med 2006; 23: 857– 866. 16911623
  3. [4]Staines A, Hanif S, Ahmed S, McKinney PA, Shera S, Bodansky HJ. Incidence of insulin dependent diabetes mellitus in Karachi, Pakistan. Arch Dis Child. 1997 2; 76(2): 121– 3. 9068300 PMC1717064
  4. [5]Shera AS, Miyan Z, Basit A, Maqsood A, Ahmadani MY, Fawwad A, Trends of type 1 diabetes in Karachi, Pakistan. Pediatr Diabetes. 2008 8; 9(4 Pt 2): 401– 6. doi: 10.1111/j.1399-5448.2007.00309.x. 18221426 · DOI
  5. [6]Fatima A, Khawaja KI, Burney S, Minhas K, Mumtaz U, Masud F. Type 1 and type 2 diabetes mellitus: are they mutually exclusive? Singapore Med J. 2013 7; 54(7): 396– 400. 23900470
  6. [7]Lone SW, Siddiqui EU, Muhammed F, Atta I, Ibrahim MN, Raza J. Frequency, clinical characteristics and outcome of diabetic ketoacidosis in children with type-1 diabetes at a tertiary care hospital. J Pak Med Assoc. 2010; 60: 725– 9. 21381577
  7. [8]Basit A, Riaz M, Fawwad A. Improving diabetes care in developing countries: The example of Pakistan. Diabetes Res Clin Pract. 2015 2; 107(2): 224– 32. doi: 10.1016/j.diabres.2014.10.013. Epub 2014 Oct 24. 25467615 · DOI
  8. [10]WHO Multicentre Reference Study Group. WHO child growth standards: length/height-for-age, weight-for-age, weight-for-length, weight-for-height and body mass index-for-age: methods and development. Acta Paediatr Suppl. 2006 4; 450: 76– 85.16817681
  9. [11]de Onis M, Onyango AW, Borghi E, Siyam A, Nishida C, Siekmann J. Development of a WHO growth reference for school-aged children and adolescents. Bull World Health Organ. 2007 9; 85(9): 660– 7. 18026621 PMC2636412
  10. [12]Wasserfall C, Montgomery E, Yu L, Michels A, Gianani R, Pugliese A, Validation of a rapid type 1 diabetes autoantibody screening assay for community-based screening of organ donors to identify subjects at increased risk for the disease. Clin Exp Immunol. 2016 7; 185(1): 33– 41. Published online 2016 May 4. doi: 10.1111/cei.12797 27029857 PMC4908288 · DOI
  11. [13]Bentley G, Higuchi R, Hoglund B, High-resolution, high-throughput HLA genotyping by next-generation sequencing. Tissue Antigens 2009; 74: 393– 403. 19845894 PMC4205125
  12. [14]Holcomb CL, Höglund B, Anderson MW, A multi-site study using high-resolution HLA genotyping by next generation sequencing. Tissue Antigens 2011; 77: 206– 217. 21299525 PMC4205124
  13. [15]Helmberg W, Lanzer G, Zahn R, Weinmayr B, Wagner T, Albert E. Virtual DNA analysis – a new tool for combination and standardised evaluation of SSO, SSP and sequencing-based typing results. Tissue Antigens. 1998 6; 51(6): 587– 92. 9694350
  14. [16]Benaglia T, Chauveau D, Hunter DR, Young D. mixtools: An R package for analysing finite mixture models. J Stat Softw 2009; 32: 1– 29.
  15. [17]Pappas DJ, Marin W, Hollenbach JA, Mack SJ. Bridging ImmunoGenomic Data Analysis Workflow Gaps (BIGDAWG): An integrated case-control analysis pipeline. Hum Immunol. 2016 3; 77(3): 283– 287. doi: 10.1016/j.humimm.2015.12.006. Epub 2015 Dec 18. 26708359 PMC4828284 · DOI
  16. [18]Hollenbach JA, Mack SJ, Thomson G, Gourraud PA. Analytical methods for disease association studies with immunogenetic data. Methods Mol Biol. 2012; 882: 245– 66. doi: 10.1007/978-1-61779-842-9_14. 22665238 PMC4209949 · DOI
  17. [19]Lancaster AK, Single RM, Solberg OD, Nelson MP, Thomson G. PyPop update--a software pipeline for large-scale multilocus population genomics. Tissue Antigens. 2007 4; 69 Suppl 1: 192– 7. 17445199 PMC4369784
  18. [20]Guo SW, Thompson EA. Performing the exact test of Hardy-Weinberg proportion for multiple alleles. Biometrics. 1992 6; 48(2): 361– 72. 1637966
  19. [21]Chen JJ, Thomson G. The variance for the disequilibrium coefficient in the individual Hardy-Weinberg test. Biometrics. 1999 12; 55(4): 1269– 72. 11315081
  20. [22]Chen JJ, Hollenbach JA, Trachtenberg EA, Hardy-Weinberg testing for HLA class II (DRB1, DQA1, DQB1, and DPB1) loci in 26 human ethnic groups. Tissue Antigens. 1999 12; 54(6): 533– 42. 10674966
  21. [24]Kanga U, Tandon N, Marwaha RK, Khanna R, Bhattacharya B, Singh S Immunogenetic association and thyroid autoantibodies in juvenile autoimmune thyroiditis in North India. Clin Endocrinol (Oxf) 2006; 64: 573– 579. 16649979
  22. [25]Sterky G, Holmgren H, Gustavson KH, Larsson Y, Lundmark KM, Nilssom KO The incidence of diabetes mellitus in Swedish children 1970–1975. Acta Paediatr Scand 1978; 67: 139– 143. 626073
  23. [26]Demir F, Günöz H, Saka N, Darendeliler F, Bundak R, Baş F Epidemiological features of type 1 diabetic patients between 0 and 18 years of age in Istanbul City. J Res Clin Pediatr Endocrinol 2015; 7: 49– 56. PMC4439892 25800476
  24. [27]Kalra S, Kalra B, Sharma A. Prevalence of type 1 diabetes mellitus in Karnal district, Haryana state, India. Diabetol Metab Syndr. 2010 3 9; 2: 14. doi: 10.1186/1758-5996-2-14. 20214794 PMC2844357 · DOI
  25. [28]Dayal D, Saini AG, Jayashree M, Singhi S, Kumar R, Samprati M, Hospital based incidence, patterns of presentation and outcome of type 1 diabetes: 12 years’ data from a tertiary care center in North India. Int J Diabetes Dev Ctries. 2015; 35: 103– 07.
  26. [29]Bhatia V, Arya V, Dabadghao P, Balasubramanian K, Sharma K, Verghese N, Etiology and outcome of childhood and adolescent diabetes mellitus in North India. J Pediatr Endocrinol Metab. 2004 7; 17(7): 993– 9. 15301047
  27. [30]Karvonen M, Pitkäniemi M, Pitkäniemi J, Kohtamäki K, Simola E, Tajima N Sex-difference in the incidence of insulin-dependent diabetes mellitus. An analysis of the recent epidemiological data. Diab Metab Rev 1997; 13: 275– 291. 9509279
  28. [31]World Population Review. (2018- 05–20). Pakistan Population 2018. Retrieved May 20, 2018 from http://worldpopulationreview.com/countries/pakistan-population/.
  29. [33]Ramachandran A, Snehalatha C, Krishnaswamy CV. Incidence of IDDM in children in urban population in southern India. Madras IDDM Registry Group Madras, South India. Diabetes Res Clin Pract. 1996 10; 34(2): 79– 82. 9031809
  30. [34]Harron KL, McKinney PA, Feltbower RG, Bodansky HJ, Norman PD, Campbell FM, Incidence rate trends in childhood type 1 diabetes in Yorkshire, UK 1978–2007: effects of deprivation and age at diagnosis in the South Asian and non-South Asian populations. Diabet Med. 2011 12; 28(12): 1508– 13. doi: 10.1111/j.1464-5491.2011.03413.x. 21838766 · DOI
  31. [35]Ji J, Hemminki K, Sundquist J, Sundquist K. Ethnic differences in incidence of type 1 diabetes among second generation immigrants and adoptees from abroad. J Clin Endocrinol Metab. 2010 2; 95(2): 847– 50. doi: 10.1210/jc.2009-1818. Epub 2009 Dec 18. 20022988 · DOI
  32. [36]Katsarou A, Gudbjörnsdottir S, Rawshani A, Dabelea D, Bonifacio E, Anderson BJ, Type 1 diabetes mellitus. Nat Rev Dis Primers. 2017 3 30; 3: 17016. doi: 10.1038/nrdp.2017.16. 28358037 · DOI · Paper page
  33. [37]Usher-Smith JA, Thompson M, Ercole A, Walter FM. Variation between countries in the frequency of diabetic ketoacidosis at first presentation of type 1 diabetes in children: a systematic review. Diabetologia. 2012 11; 55(11): 2878– 94. doi: 10.1007/s00125-012-2690-2. Epub 2012 Aug 30. 22933123 PMC3464389 · DOI
  34. [39]Jones AG, Hattersley AT. The clinical utility of C-peptide measurement in the care of patients with diabetes. Diabet Med. 2013 7; 30(7): 803– 17. doi: 10.1111/dme.12159. 23413806 PMC3748788 · DOI
  35. [40]Shivaprasad C, Mittal R, Dharmalingam M, Kumar PK. Zinc transporter-8 autoantibodies can replace IA-2 autoantibodies as serological marker for juvenile onset type 1 diabetes in India. Indian J Endocrinol Metab. 2014 5; 18(3): 345– 9. doi: 10.4103/2230-8210.131174. 24944929 PMC4056133 · DOI
  36. [41]Goswami R, Kochupillai N, Gupta N, Kukreja A, Lan M, Maclaren NK. Islet cell autoimmunity in youth onset diabetes mellitus in northern India. Diabetes Res Clin Pract. 2001 7; 53(1): 47– 54. 11378213
  37. [42]Singh AK, Bhatia E, Dabadghao P, Bhatia V, Gellert A, Colman PG. Role of islet autoantibody in the aetiology of different clinical subtypes of diabetes mellitus in young north Indians. Diabet Med. 2000 4; 17(4): 275– 80. 10821293
  38. [43]Balasubramanian K, Dabadghao P, Bhatia V, Colman PG, Gellert SA, Bharadwaj U, High frequency of type 1B (idiopathic) diabetes in North Indian children with recent-onset diabetes. Diabetes Care. 2003 9; 26(9): 2697. 12941746
  39. [44]Dayal D, Samprati M, Kaur N, Minz RW, Jayaraman D. Prevalence of beta-cell, thyroid and celiac autoimmunity in North Indian children with recent onset type 1 diabetes (T1D). J Clin Diagn Res. 2015 3; 9(3): SM01– 2. doi: 10.7860/JCDR/2015/11960.5711. Epub 2015 Mar 1. 25954678 PMC4413128 · DOI
  40. [45]Tandon N, Shtauvere-Brameus A, Hagopian WA, Sanjeevi CB. Prevalence of ICA-12 and other autoantibodies in north Indian patients with early-onset diabetes. Ann N Y Acad Sci. 2002 4; 958: 214– 7. 12021109
  41. [46]Dabelea D, Pihoker C, Talton JW, D’Agostino RB Jr, Fujimoto W, Klingensmith GJ, Etiological approach to characterization of diabetes type: the SEARCH for Diabetes in Youth Study. Diabetes Care. 2011 7; 34(7): 1628– 33. doi: 10.2337/dc10-2324. Epub 2011 Jun 2. 21636800 PMC3120176 · DOI
  42. [48]Basit A, Fawwad A, Qureshi H, Shera AS, NDSP Members. Prevalence of diabetes, pre-diabetes and associated risk factors: Second National Diabetes Survey of Pakistan (NDSP), 2016–17. Accepted for publication, BMJ Open 2018. PMC6078264 30082350
  43. [49]Unnikrishnan R, Mohan V. Fibrocalculous pancreatic diabetes (FCPD). Acta Diabetol. 2015 2; 52(1): 1– 9. doi: 10.1007/s00592-014-0685-9. Epub 2014 Nov 14. 25395047 · DOI
  44. [50]Kelly MA, Alvi NS, Croft NJ, Mijovic CH, Bottazzo GF, Barnett AH. Genetic and immunological characteristics of type 1 diabetes mellitus in an Indo-Aryan population. Diabetologia. 2000 4; 43(4): 450– 6. 10819238
  45. [51]Rasmussen T, Yap SE, Stray-Pedersen B, Akselsen HE, McKinney PA, Rønningen KS. HLA associated type 1 diabetes risk in children of Pakistani migrants to Norway. Med Hypotheses. 2014 12; 83(6): 664– 7. doi: 10.1016/j.mehy.2014.09.013. Epub 2014 Oct 17. 25441839 · DOI
  46. [52]Sunni M, Noble JA, Yu L, Mahamed Z, Lane JA, Dhunkal AM, Predominance of DR3 in Somali children with type 1 diabetes in the twin cities, Minnesota. Pediatr Diabetes. 2017 3; 18(2): 136– 142. doi: 10.1111/pedi.12369. Epub 2016 Feb 8. 26854192 · DOI
  47. [53]Kiani AK, John P, Bhatti A, Zia A, Shahid G, Akhtar P, Association of 32 type 1 diabetes risk loci in Pakistani patients. Diabetes Res Clin Pract. 2015 4; 108(1): 137– 42. doi: 10.1016/j.diabres.2015.01.022. Epub 2015 Jan 21. 25661663 · DOI

Cited by

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Authors
Fawwad, A., Govender, D., Ahmedani, M. Y., Basit, A., Lane, J. A., Mack, S. J., Atkinson, M. A., Henry Wasserfall, C., Ogle, G. D., & Noble, J. A.
Affiliations
  • Baqai Medical University (PK)
  • The University of Sydney (AU)
  • Baqai Institute of Diabetology and Endocrinology (PK)
  • University of Florida Health (US)
Corresponding author
  • Fawwad, Asher
  • Govender, Denira
  • Ahmedani, Mohammad Yakoob
  • Basit, Abdul
  • Lane, Julie Ann
  • Mack, Steven John
  • Atkinson, Mark Alvin
  • Ogle, Graham David
  • Noble, Janelle Annette
Venue
Diabetes Research and Clinical Practice
Publisher
Elsevier BV
Published
2019-03
Volume
149
Pages
9-17
ISSN
0168-8227 (ISSN-L)
OpenAlex
W2913435029
Cited by
20
References
3
Citations by year
2026: 1 · 2025: 1 · 2024: 5 · 2023: 2 · 2022: 4 · 2021: 2 · 2020: 3 · 2019: 2
FWCI
1.66
Type
journal article
Language
en
Open access
Locations
  • Diabetes Research and Clinical Practice (acceptedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • Leona M. and Harry B. Helmsley Charitable Trust
  • National Institutes of Health
  • NIAID (R01AI28775)
  • NIH
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords
type 1 diabetes, youth-onset diabetes, HLA-DRB1, HLA-DRB1*0301, autoantibodies, GAD65, IA-2, C-peptide, HbA1c, children and adolescents, Pakistan, genetic susceptibility
MeSH terms
Adolescent, Adult, Autoantibodies, C-Peptide, Child, Child, Preschool, Diabetes Mellitus, Type 1, Female, Humans, Infant, Male, Pakistan, Young Adult, HLA-DRB1 Chains

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