Characteristics of rapid vs slow progression to type 1 diabetes in multiple islet autoantibody-positive children
Open accessAbstract
Aims/hypothesis Islet autoantibody-positive children progress to type 1 diabetes at variable rates. In our study, we asked whether characteristic autoantibody and/or gene profiles could be defined for phenotypes showing extreme progression.Methods Autoantibodies to insulin (IAA), GAD (GADA), insulinoma-associated antigen-2 (IA-2A) and zinc transporter 8 (ZnT8A) were measured in follow-up sera, and genotyping for type 1 diabetes susceptibility genes (HLA-DR/HLA-DQ, INS variable number of tandem repeats [VNTR] and single nucleotide polymorphisms at PTPN22, PTPN2, ERBB3, IL2, SH2B3, CTLA4, IFIH1, KIAA0350 [also known as CLEC16A], CD25, IL18RAP, IL10, COBL) was performed on the DNA samples of children born to a parent with type 1 diabetes and prospectively followed from birth for up to 22 years.Results Of the 1,650 children followed, 23 developed multiple autoantibodies and progressed to diabetes within 3 years (rapid progressors), while 24 children developed multiple autoantibodies and remained non-diabetic for more than 10 years from seroconversion (slow progressors). Rapid and slow progressors were similar with respect to HLA-DR/HLA-DQ genotypes, development of IAA, GADA and ZnT8A, and progression to multiple autoantibodies. In contrast, IA-2A development was considerably delayed in the slow progressors. Furthermore, both groups were effectively distinguished by the combined presence or absence of type 1 diabetes susceptibility alleles of non-HLA genes, most notably IL2, CD25, INS VNTR, IL18RAP, IL10, IFIH1 and PTPN22, and discrimination was improved among children carrying high-risk HLA-DR/HLA-DQ genotypes.Conclusions/interpretation Our data suggest that genotypes of non-HLA type 1 diabetes susceptibility genes influence the likelihood or rate of diabetes progression among children with multiple islet autoantibodies.
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?
The existence of slow progressors demonstrates that the rate of islet beta-cell death can vary greatly between individuals before T1D or T2D diagnosis, enabling some individuals to remain disease-free for longer, possibly by similar mechanisms.
“This demonstrates that the rate of islet beta-cell death can vary greatly between individuals before T1D or T2D diagnosis, enabling some individuals to remain disease-free for longer, possibly by similar mechanisms.”
From A review of current trends with type 2 diabetes epidemiology, aetiology, pathogenesis, treatments and future perspectives (2021) · cites this paper as [100]
There have been reports of individuals who do not progress to T1D for >10 years despite persistent islet autoimmunity (slow progressors).
“Interestingly, there have been reports of individuals who do not progress to T1D for >10 years despite persistent islet autoimmunity (slow progressors).100”
From A review of current trends with type 2 diabetes epidemiology, aetiology, pathogenesis, treatments and future perspectives (2021) · cites this paper as [100]
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
A new look at the statistical model identification
Akaike, H. (1974) · IEEE Transactions on Automatic Control · doi:10.1109/tac.1974.1100705 · Cited by 51,879 · see citing works
ANew Look at the Statistical Model Identification
AKAlKE, H. (2011) · Cited by 4,177 · see citing works
Christakis, D., Richards, J. A., Zimmerman, F. J., Garrison, M. M., Xu, D., & Yapanel, U. H. (2009) · Cited by 2,290 · see citing works
Patterson, C. C., Dahlquist, G. G., Gyürüs, E., Green, A., & Soltész, G. (2009) · The Lancet · doi:10.1016/s0140-6736(09)60568-7 · Cited by 1,854 · see citing works
The Type 1 Diabetes Genetics Consortium, Barrett, J. C., Clayton, D. G., Concannon, P., Akolkar, B., Cooper, J. D., Erlich, H. A., Julier, C., Morahan, G., Nerup, J., et al. (2009) · Nature Genetics · doi:10.1038/ng.381 · Cited by 1,746 · see citing works
Type 1 diabetes: new perspectives on disease pathogenesis and treatment
Atkinson, M. A., & Eisenbarth, G. S. (2001) · The Lancet · doi:10.1016/s0140-6736(01)05415-0 · Cited by 1,491 · see citing works
Nejentsev, S., Walker, N., Riches, D., Egholm, M., & Todd, J. A. (2009) · Science · doi:10.1126/science.1167728 · Cited by 958 · see citing works
Verge, C. F., Gianani, R., Kawasaki, E., Yu, L., Pietropaolo, M., Chase, H. P., Eisenbarth, G. S., & Jackson, R. A. (1996) · Diabetes · doi:10.2337/diab.45.7.926 · Cited by 827 · see citing works
Shared and Distinct Genetic Variants in Type 1 Diabetes and Celiac Disease
Smyth, D. J., Plagnol, V., Walker, N. M., Cooper, J. D., Downes, K., Yang, J. H. M., Howson, J. M. M., Stevens, H. E., McManus, R., Wijmenga, C., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0807917 · Cited by 738 · see citing works
Central Role of Defective Interleukin-2 Production in the Triggering of Islet Autoimmune Destruction
Tang, Q., Adams, J. Y., Penaranda, C., Melli, K., Piaggio, E., Sgouroudis, E., Piccirillo, C. A., Salomon, B. L., & Bluestone, J. A. (2008) · Immunity · doi:10.1016/j.immuni.2008.03.016 · Cited by 729 · see citing works
Autoimmune-associated lymphoid tyrosine phosphatase is a gain-of-function variant
Vang, T., Congia, M., Macis, M. D., Musumeci, L., Orrù, V., Zavattari, P., Nika, K., Tautz, L., Taskén, K., Cucca, F., et al. (2005) · Nature Genetics · doi:10.1038/ng1673 · Cited by 724 · see citing works
Smyth, D. J., Cooper, J. D., Bailey, R., Field, S., Burren, O. S., Smink, L. J., Guja, C., Ionescu-Tirgoviste, C., Widmer, B., Dunger, D. B., et al. (2006) · Nature Genetics · doi:10.1038/ng1800 · Cited by 688 · see citing works
Ziegler, A., Hummel, M., Schenker, M., & Bonifacio, E. E. (1999) · Diabetes · doi:10.2337/diabetes.48.3.460 · Cited by 640 · see citing works
Self-citationLocalization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A
Nejentsev, S., Howson, J. M. M., Walker, N. M., Szeszko, J. S., Field, S. F., Stevens, H. E., Reynolds, P., Hardy, M. P., King, E., Masters, J., et al. (2007) · Nature · doi:10.1038/nature06406 · Cited by 568 · see citing works
Todd, J. A. (2010) · Immunity · doi:10.1016/j.immuni.2010.04.001 · Cited by 560 · see citing works
Bingley, P. J., Christie, M. R., Bonifacio, E. E., Bonfanti, R., Shattock, M., Fonte, M.-T., Bottazzo, G.-F., & Gale, E. A. (1994) · Diabetes · doi:10.2337/diab.43.11.1304 · Cited by 384 · see citing works
Interleukin-2 gene variation impairs regulatory T cell function and causes autoimmunity
Yamanouchi, J., Rainbow, D., Serra, P., Howlett, S., Hunter, K. M. D., Garner, V. E. S., González-Muñoz, A., Clark, J., Veijola, R., Cubbon, R. M., et al. (2007) · Nature Genetics · doi:10.1038/ng1958 · Cited by 367 · see citing works
Quantification of islet-cell antibodies and prediction of insulin-dependent diabetes
Bonifacio, E. E., Shattock, M., Dean, B. M., Bottazzo, G. F., Bingley, P. J., Gale, E., & Dunger, D. B. (1990) · The Lancet · doi:10.1016/0140-6736(90)90013-u · Cited by 344 · see citing works
Kulmala, P., Savola, K., Petersen, J. S., Vähäsalo, P., Karjalainen, J., Löppönen, T., Dyrberg, T., Åkerblom, H. K., & Knip, M. (1998) · Journal of Clinical Investigation · doi:10.1172/jci119879 · Cited by 284 · see citing works
Törn, C., Mueller, P. W., Schlosser, M., Bonifacio, E., Bingley, P. J., & Laboratories, P. (2008) · Diabetologia · doi:10.1007/s00125-008-0967-2 · Cited by 284 · see citing works
Long, S. A., Cerosaletti, K. M., Bollyky, P. L., Tatum, M., Shilling, H. G., Zhang, S., Zhang, Z., Pihoker, C., Sanda, S., Greenbaum, C. J., et al. (2009) · Diabetes · doi:10.2337/db09-0694 · Cited by 284 · see citing works
Clinical Applications of Diabetes Antibody Testing
Bingley, P. J. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-1365 · Cited by 278 · see citing works
Stratification of Type 1 Diabetes Risk on the Basis of Islet Autoantibody Characteristics
Achenbach, P., Warncke, K., Reiter, J., Naserke, H. E., Williams, A. J. K., Bingley, P. J., Bonifacio, E. E., & Ziegler, A. (2004) · Diabetes · doi:10.2337/diabetes.53.2.384 · Cited by 276 · see citing works
Self-citationDendrou, C. A., Plagnol, V., Fung, E., Yang, J. H. M., Downes, K., Cooper, J. D., Nutland, S., Coleman, G., Himsworth, M., Hardy, M., et al. (2009) · Nature Genetics · doi:10.1038/ng.434 · Cited by 274 · see citing works
Transcription of the IL10 gene reveals allele-specific regulation at the mRNA level
Kurreeman, F. A. S., Schonkeren, J. J. M., Heijmans, B. T., Toes, R. E. M., & Huizinga, T. W. J. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh187 · Cited by 262 · see citing works
Achenbach, P., Koczwara, K., Knopff, A., Naserke, H. E., Ziegler, A., & Bonifacio, E. E. (2004) · Journal of Clinical Investigation · doi:10.1172/jci21307 · Cited by 238 · see citing works
Self-citationParikka, V., Näntö-Salonen, K., Saarinen, M., Simell, T., Ilonen, J., Hyöty, H., Veijola, R., Knip, M., & Simell, O. (2012) · Diabetologia · doi:10.1007/s00125-012-2523-3 · Cited by 235 · see citing works
Verge, C. F., Gianani, R., Kawasaki, E., et al. (1996) · Diabetes · doi:10.2337/diabetes.45.7.926 · Cited by 228 · see citing works
Understanding type 1 diabetes through genetics: advances and prospects
Polychronakos, C., & Li, Q. (2011) · Nature Reviews Genetics · doi:10.1038/nrg3069 · Cited by 226 · see citing works
Puavilai, G., Chanprasertyotin, S., & Sriphrapradaeng, A. (1999) · Diabetes Research and Clinical Practice · doi:10.1016/s0168-8227(99)00008-x · Cited by 221 · see citing works
Autoantibodies to zinc transporter 8 and SLC30A8 genotype stratify type 1 diabetes risk
Achenbach, P., Lampasona, V., Landherr, U., Koczwara, K., Krause, S. W., Grallert, H., Winkler, C., Pflüger, M., Illig, T., Bonifacio, E. E., et al. (2009) · Diabetologia · doi:10.1007/s00125-009-1438-0 · Cited by 197 · see citing works
Self-citationSteck, A. K., Johnson, K., Barriga, K. J., Miao, D., Yu, L., Hutton, J. C., Eisenbarth, G. S., & Rewers, M. J. (2011) · Diabetes Care · doi:10.2337/dc10-2088 · Cited by 195 · see citing works
Diabetes Antibody Standardization Program: evaluation of assays for insulin autoantibodies
Laboratories, P., Schlosser, M., Mueller, P. W., Törn, C., Bonifacio, E. E., & Bingley, P. J. (2010) · Diabetologia · doi:10.1007/s00125-010-1915-5 · Cited by 180 · see citing works
Hummel, M., Bonifacio, E. E., Schmid, S., Walter, M., Knopff, A., & Ziegler, A. (2004) · Annals of Internal Medicine · doi:10.7326/0003-4819-140-11-200406010-00009 · Cited by 151 · see citing works
Self-citationExact Inference for Contingency Tables with Ordered Categories
Agresti, A., Mehta, C. R., & Patel, N. R. (1990) · Journal of the American Statistical Association · doi:10.1080/01621459.1990.10476220 · Cited by 133 · see citing works
FUT2 Nonsecretor Status Links Type 1 Diabetes Susceptibility and Resistance to Infection
Smyth, D. J., Cooper, J. D., Howson, J. M. M., Pamela, C., Downes, K., Mistry, T., Stevens, H. E., Walker, N. M., & Todd, J. A. (2011) · Diabetes · doi:10.2337/db11-0638 · Cited by 133 · see citing works
Bingley, P. J., Christie, M. R., Bonifacio, E. E., et al. (1994) · Diabetes · doi:10.2337/diabetes.43.11.1304 · Cited by 118 · see citing works
Lampasona, V., Schlosser, M., Mueller, P. W., Williams, A. J. K., Wenzlau, J. M., Hutton, J. C., Achenbach, P., & Laboratories, P. (2011) · Clinical Chemistry · doi:10.1373/clinchem.2011.170662 · Cited by 109 · see citing works
Self-citationWalter, M., Albert, E. D., Conrad, M., Keller, E., Hummel, M., Ferber, K. M., Barratt, B. J., Todd, J. A., Ziegler, A., & Bonifacio, E. E. (2003) · Diabetologia · doi:10.1007/s00125-003-1082-z · Cited by 106 · see citing works
Self-citationSosenko, J. M., Krischer, J. P., Palmer, J. P., Mahon, J. L., Cowie, C. C., Greenbaum, C. J., Cuthbertson, D. D., Lachin, J. M., Skyler, J. S., & the Diabetes Prevention Trial–Type 1 Study Group (2008) · Diabetes Care · doi:10.2337/dc07-1459 · Cited by 104 · see citing works
IA-2 autoantibodies predict impending Type I diabetes in siblings of patients
Decochez, K., Leeuw, I. D., Keymeulen, B., Mathieu, C., Rottiers, R., Weets, I., Vandemeulebroucke, E., Truyen, I., Kaufman, L., Schuit, F. C., et al. (2002) · Diabetologia · doi:10.1007/s00125-002-0949-8 · Cited by 95 · see citing works
Mayr, A., Schlosser, M., Grober, N., Kenk, H., Ziegler, A. G., Bonifacio, E. E., & Achenbach, P. (2007) · Diabetes · doi:10.2337/db06-1715 · Cited by 89 · see citing works
Self-citationZiegler, A., Pflueger, M., Winkler, C., Achenbach, P., Akolkar, B., Krischer, J. P., & Bonifacio, E. E. (2011) · Journal of Autoimmunity · doi:10.1016/j.jaut.2011.02.004 · Cited by 81 · see citing works
Self-citationEpigenetics: deciphering how environmental factors may modify autoimmune type 1 diabetes
MacFarlane, A. J., Strom, A., & Scott, F. W. (2009) · Mammalian Genome · doi:10.1007/s00335-009-9213-6 · Cited by 75 · see citing works
Evidence of Gene-Gene Interaction and Age-at-Diagnosis Effects in Type 1 Diabetes
Howson, J. M. M., Cooper, J. D., Smyth, D. J., Walker, N. M., Stevens, H. E., She, J., Eisenbarth, G. S., Rewers, M., Todd, J. A., Akolkar, B., et al. (2012) · Diabetes · doi:10.2337/db11-1694 · Cited by 72 · see citing works
Sgouroudis, E., Albanese, A., & Piccirillo, C. A. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.9.6283 · Cited by 69 · see citing works
Winkler, C., Krumsiek, J., Lempainen, J., Achenbach, P., Grallert, H., Giannopoulou, E., Bunk, M., Theis, F. J., Bonifacio, E., & Ziegler, A.-G. (2012) · Genes & Immunity · doi:10.1038/gene.2012.36 · Cited by 68 · see citing works
Self-citationvon Herrath, M. (2009) · Nature · doi:10.1038/459518a · Cited by 59 · see citing works
Walter, U., Toepfer, T., Dittmar, K. E. J., Kretschmer, K., Lauber, J., Weiss, S., Servos, G., Lechner, O., Scherbaum, W. A., Bornstein, S., et al. (2003) · Diabetologia · doi:10.1007/s00125-003-1164-y · Cited by 48 · see citing works
IA-2 autoantibody affinity in children at risk for type 1 diabetes
Krause, S., Chmiel, R., Bonifacio, E. E., Scholz, M., Powell, M. J., Furmaniak, J., Smith, B. R., Ziegler, A., & Achenbach, P. (2012) · Clinical Immunology · doi:10.1016/j.clim.2012.09.010 · Cited by 25 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Insel, R. A., Dunne, J. L., Atkinson, M. A., Chiang, J. L., Dabelea, D., Gottlieb, P. A., Greenbaum, C. J., Herold, K. C., Krischer, J. P., Lernmark, Å., et al. (2015) · Diabetes Care · doi:10.2337/dc15-1419 · Cited by 1,216 · see citing works
Self-citationReed, J., Bain, S., & Kanamarlapudi, V. (2021) · Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy · doi:10.2147/dmso.s319895 · Cited by 441 · see citing works
Early prediction of autoimmune (type 1) diabetes.
Regnell, S. E., & Lernmark, Å. (2017) · Diabetologia · doi:10.1007/s00125-017-4308-1 · Cited by 195 · see citing works
- Authors
- Achenbach, P., Hummel, M., Thümer, L., Boerschmann, H., Höfelmann, D., & Ziegler, A. G.
- Affiliations
- Helmholtz Munich (DE)
- TUM Klinikum (DE)
- Corresponding author
- Achenbach, P.
- Ziegler, A. G.
- Venue
- Diabetologia
- Published
- 2013-03-29
- Volume
- 56
- Issue
- 7
- Pages
- 1615-1622
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W2095042565
- Cited by
- 76
- References
- 50
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 3 · 2023: 4 · 2022: 2 · 2021: 5 · 2020: 5 · 2019: 8 · 2018: 6 · 2017: 11 · 2016: 7 · 2015: 7 · 2014: 7 · 2013: 3
- FWCI
- 5.30
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Site cant be reached (submittedVersion)
- Funders
- Bundesministerium für Bildung und Forschung (FKZ 01GI0805, 01GI0805)
- Technische Universität Dresden
- Technische Universität München
- Helmholtz Zentrum München
- 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, disease progression, islet autoantibodies, insulin autoantibodies, glutamic acid decarboxylase antibodies, IA-2 autoantibodies, zinc transporter 8 autoantibodies, PTPN22, interleukin-2, CD25, IL18RAP, IL-10, MDA5, seroconversion
- MeSH terms
- Interferon-Induced Helicase, IFIH1, Zinc Transporter 8, Adolescent, Autoantibodies, Child, Child, Preschool, Diabetes Mellitus, Type 1, Female, Genotype, HLA-DQ Antigens, Humans, Infant, Infant, Newborn, Insulin, Male, Microfilament Proteins, Monosaccharide Transport Proteins, Proteins, Interleukin-10, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Receptor, ErbB-3, Cation Transport Proteins, Lectins, C-Type, Intracellular Signaling Peptides and Proteins, Adaptor Proteins, Signal Transducing, DEAD-box RNA Helicases, Interleukin-2 Receptor alpha Subunit, Interleukin-18 Receptor beta Subunit, Protein Tyrosine Phosphatase, Non-Receptor Type 2, Protein Tyrosine Phosphatase, Non-Receptor Type 22, Receptor-Like Protein Tyrosine Phosphatases, Class 8, CTLA-4 Antigen
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
