Clinical features, biochemistry and HLA-DRB1 status in youth-onset type 1 diabetes in Pakistan
Open accessAbstract
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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Incidence of diabetes in youth in the United States
SEARCH for Diabetes in Youth Study Group*, T. W. G. F. T. (2007) · JAMA · doi:10.1001/jama.297.24.2716 · Cited by 991 · see citing works
HLA DR-DQ Haplotypes and Genotypes and Type 1 Diabetes Risk
Erlich, H., Valdes, A. M., Noble, J., Carlson, J. A., Varney, M., Concannon, P., Mychaleckyj, J. C., Todd, J. A., Bonella, P., Fear, A. L., et al. (2008) · Diabetes · doi:10.2337/db07-1331 · Cited by 790 · cited 3× · see citing works
“Notably, the similar European haplotype DRB1*14:01~DQB1*05:01 exhibits a very strong protective association with T1D (23).”
BackgroundResultSelf-citationDeriving ethnic-specific BMI cutoff points for assessing diabetes risk.
Chiu, M., Austin, P. C., Manuel, D. G., Shah, B. R., & Tu, J. V. (2011) · Diabetes Care · doi:10.2337/dc10-2300 · Cited by 398 · see citing works
Flagged first, then by citations
Research works printed but not linked: 47
- [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]DIAMOND Project Group. Incidence and trends of childhood type 1 diabetes worldwide 1990–1999. Diabet Med 2006; 23: 857– 866. 16911623
- [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
- [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
- [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
- [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
- [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
- [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
- [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
- [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
- [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
- [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
- [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
- [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.
- [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
- [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
- [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
- [20]Guo SW, Thompson EA. Performing the exact test of Hardy-Weinberg proportion for multiple alleles. Biometrics. 1992 6; 48(2): 361– 72. 1637966
- [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
- [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
- [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
- [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
- [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
- [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
- [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.
- [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
- [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
- [31]World Population Review. (2018- 05–20). Pakistan Population 2018. Retrieved May 20, 2018 from http://worldpopulationreview.com/countries/pakistan-population/.
- [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
- [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
- [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
- [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
- [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
- [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
- [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
- [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
- [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
- [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
- [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
- [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
- [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
- [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
- [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
- [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
- [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
- [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
- [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
Sorted by citations
Haller, M. J., Bell, K. J., Besser, R. E. J., Casteels, K., Couper, J. J., Craig, M. E., Elding Larsson, H., Jacobsen, L., Lange, K., Oron, T., et al. (2024) · Hormone Research in Paediatrics · doi:10.1159/000543035 · Cited by 151 · see citing works
The epidemiology of type 1 diabetes mellitus in older adults
Tomic, D., Harding, J. L., Jenkins, A. J., Shaw, J. E., & Magliano, D. J. (2025) · Nature Reviews Endocrinology · doi:10.1038/s41574-024-01046-z · Cited by 58 · see citing works
- 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
- ORCID
- Venue
- Diabetes Research and Clinical Practice
- Publisher
- Elsevier BV
- Published
- 2019-03
- Volume
- 149
- Pages
- 9-17
- ISSN
- 0168-8227 (ISSN-L)
- PMC
- PMC6456725
- 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
- bronze
- doi.org
- Licence
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review