Frequency and phenotype of type 1 diabetes in the first six decades of life: a cross-sectional, genetically stratified survival analysis from UK Biobank
Open accessAbstract
Background Type 1 diabetes is typically considered a disease of children and young adults. Genetic susceptibility to young-onset type 1 diabetes is well defined and does not predispose to type 2 diabetes. It is not known how frequently genetic susceptibility to type 1 diabetes leads to a diagnosis of diabetes after age 30 years. We aimed to investigate the frequency and phenotype of type 1 diabetes resulting from high genetic susceptibility in the first six decades of life. Methods In this cross-sectional analysis, we used a type 1 diabetes genetic risk score based on 29 common variants to identify individuals of white European descent in UK Biobank in the half of the population with high or low genetic susceptibility to type 1 diabetes. We used Kaplan-Meier analysis to evaluate the number of cases of diabetes in both groups in the first six decades of life. We genetically defined type 1 diabetes as the additional cases of diabetes that occurred in the high genetic susceptibility group compared with the low genetic susceptibility group. All remaining cases were defined as type 2 diabetes. We assessed the clinical characteristics of the groups with genetically defined type 1 or type 2 diabetes. Findings 13 250 (3·5%) of 379 511 white European individuals in UK Biobank had developed diabetes in the first six decades of life. 1286 more cases of diabetes were in the half of the population with high genetic susceptibility to type 1 diabetes than in the half of the population with low genetic susceptibility. These genetically defined cases of type 1 diabetes were distributed across all ages of diagnosis; 537 (42%) were in individuals diagnosed when aged 31–60 years, representing 4% (537/12 233) of all diabetes cases diagnosed after age 30 years. The clinical characteristics of the group diagnosed with type 1 diabetes when aged 31–60 years were similar to the clinical characteristics of the group diagnosed with type 1 diabetes when aged 30 years or younger. For individuals diagnosed with diabetes when aged 31–60 years, the clinical characteristics of type 1 diabetes differed from those of type 2 diabetes: they had a lower BMI (27·4 kg/m 2 [95% CI 26·7–28·0] vs 32·4 kg/m 2 [32·2–32·5]; p<0·0001), were more likely to use insulin in the first year after diagnosis (89% [476/537] vs 6% [648/11 696]; p<0·0001), and were more likely to have diabetic ketoacidosis (11% [61/537] vs 0·3% [30/11 696]; p<0·0001). Interpretation Genetic susceptibility to type 1 diabetes results in non-obesity-related, insulin-dependent diabetes, which presents throughout the first six decades of life. Our results highlight the difficulty of identifying type 1 diabetes after age 30 years because of the increasing background prevalence of type 2 diabetes. Failure to diagnose late-onset type 1 diabetes can have serious consequences because these patients rapidly develop insulin dependency. Funding Wellcome Trust and Diabetes UK.
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?
Type 1 diabetes can occur at any age, with up to 50% of cases occurring in adulthood.
“the disease can occur at any age, with up to 50% of cases occurring in adulthood.7”
From Type 1 diabetes (2018) · cites this paper as [7]
The very strong relationship between type 2 diabetes incidence and age means that even classical features of type 1 diabetes may have limited predictive value in older adults.
“The very strong relationship between type 2 diabetes incidence and age means that even”
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
Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls
The Wellcome Trust Case Control Consortium, Management Committee, Burton, P. R., Clayton, D. G., Cardon, L. R., Craddock, N., Deloukas, P., Duncanson, A., Kwiatkowski, D. P., McCarthy, M. I., et al. (2007) · Nature · doi:10.1038/nature05911 · Cited by 9,442 · see citing works
Self-citationHusby, S., Koletzko, S., Korponay‐Szabó, I. R., Mearin, M. L., Phillips, A., Shamir, R., Troncone, R., Giersiepen, K., Branski, D., Catassi, C., et al. (2012) · Journal of Pediatric Gastroenterology and Nutrition · doi:10.1097/mpg.0b013e31821a23d0 · Cited by 2,683 · see citing works
the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium, Morris, A. P., Voight, B. F., Teslovich, T. M., Ferreira, T., Segrè, A. V., Steinthorsdottir, V., Strawbridge, R. J., Khan, H., Grallert, H., et al. (2012) · Nature Genetics · doi:10.1038/ng.2383 · Cited by 1,912 · see citing works
Self-citationThe 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
Epidemiology of type 1 diabetes
Maahs, D. M., West, N. A., Lawrence, J. M., & Mayer-Davis, E. J. (2010) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2010.05.011 · Cited by 1,092 · see citing works
Ankylosing Spondylitis and Axial Spondyloarthritis
Taurog, J. D., Chhabra, A. B., & Colbert, R. A. (2016) · New England Journal of Medicine · doi:10.1056/nejmra1406182 · Cited by 930 · see citing works
The many faces of diabetes: a disease with increasing heterogeneity
Tuomilehto, J., Santoro, N., Caprio, S., Cai, M., Weng, J., & Groop, L. (2013) · The Lancet · doi:10.1016/s0140-6736(13)62219-9 · Cited by 669 · see citing works
The clinical utility of C‐peptide measurement in the care of patients with diabetes
Jones, A. G., & Hattersley, A. T. (2013) · Diabetic Medicine · doi:10.1111/dme.12159 · Cited by 638 · see citing works
Self-citationAlgorithms for the Capture and Adjudication of Prevalent and Incident Diabetes in UK Biobank
Eastwood, S. V., Mathur, R., Atkinson, M. D., Brophy, S. T., Sudlow, C. L. M., Flaig, R., de Lusignan, S., Allen, N. E., & Chaturvedi, N. (2016) · PLoS ONE · doi:10.1371/journal.pone.0162388 · Cited by 475 · see citing works
UK biobank data: come and get it
Allen, N. E., Sudlow, C., Peakman, T., Collins, R., & Biobank, O. B. O. U. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3008601 · Cited by 399 · see citing works
Height, body mass index, and socioeconomic status: mendelian randomisation study in UK Biobank
Tyrrell, J., Jones, S. E., Beaumont, R. N., Astley, C. M., Lovell, R., Yaghootkar, H., Tuke, M. A., Ruth, K. S., Freathy, R. M., Hirschhorn, J. N., et al. (2016) · BMJ · doi:10.1136/bmj.i582 · Cited by 363 · see citing works
Self-citationOram, R. A., Patel, K., Hill, A., Shields, B. M., McDonald, T. J., Jones, A. G., Hattersley, A. T., & Weedon, M. N. (2015) · Diabetes Care · doi:10.2337/dc15-1111 · Cited by 351 · see citing works
Self-citationGillespie, K. M., Bain, S. C., Barnett, A. H., Bingley, P. J., Christie, M. R., Gill, G. V., & Gale, E. A. (2004) · The Lancet · doi:10.1016/s0140-6736(04)17357-1 · Cited by 304 · see citing works
Global epidemiology of type 1 diabetes in young adults and adults: a systematic review
Diaz-Valencia, P. A., Bougnères, P., & Valleron, A.-J. (2015) · BMC Public Health · doi:10.1186/s12889-015-1591-y · Cited by 294 · 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
Prediction and Interaction in Complex Disease Genetics: Experience in Type 1 Diabetes
Clayton, D. G. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000540 · Cited by 252 · see citing works
HLA-DQ typing in the diagnosis of celiac disease
Kaukinen, K., Partanen, J., Mäki, M., & Collin, P. (2002) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2002.05471.x · Cited by 243 · see citing works
Viral Load Kinetics of MERS Coronavirus Infection
Oh, M., Park, W. B., Choe, P. G., Choi, S., Kim, J., Chae, J., Park, S. S., Kim, E.-C., Oh, H. S., Kim, E. J., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmc1511695 · Cited by 224 · see citing works
Genetic, autoimmune, and clinical characteristics of childhood- and adult-onset type 1 diabetes.
Sabbah, E., Savola, K., Ebeling, T., Kulmala, P., Vähäsalo, P., Ilonen, J., Salmela, P. I., & Knip, M. (2000) · Diabetes Care · doi:10.2337/diacare.23.9.1326 · Cited by 219 · see citing works
Type 1 Diabetes Genetic Risk Score: A Novel Tool to Discriminate Monogenic and Type 1 Diabetes
Patel, K. A., Oram, R. A., Flanagan, S. E., Franco, E. D., Colclough, K., Shepherd, M. H., Ellard, S., Weedon, M. N., & Hattersley, A. T. (2016) · Diabetes · doi:10.2337/db15-1690 · Cited by 196 · see citing works
Self-citationGenetic Analysis of Adult-Onset Autoimmune Diabetes
Howson, J. M. M., Rosinger, S., Smyth, D. J., Boehm, B. O., the ADBW-END Study Group, & Todd, J. A. (2011) · Diabetes · doi:10.2337/db11-0364 · Cited by 143 · see citing works
Feature ranking of type 1 diabetes susceptibility genes improves prediction of type 1 diabetes
Winkler, C., Krumsiek, J., Buettner, F., Angermueller, C., Giannopoulou, E. Z., Theis, F. J., Ziegler, A., & Bonifacio, E. E. (2014) · Diabetologia · doi:10.1007/s00125-014-3362-1 · Cited by 136 · see citing works
Mayer-Davis, E. J., Bell, R. A., Dabelea, D., D'Agostino, R., Imperatore, G., Lawrence, J. M., Liu, L., Marcovina, S., & for the SEARCH for Diabetes in Youth Study Group (2009) · Diabetes Care · doi:10.2337/dc09-s201 · Cited by 119 · see citing works
Hope, S. V., Wienand-Barnett, S., Shepherd, M., King, S. M., Fox, C., Khunti, K., Oram, R. A., Knight, B. A., Hattersley, A. T., Jones, A. G., et al. (2016) · British Journal of General Practice · doi:10.3399/bjgp16x684961 · Cited by 87 · see citing works
Self-citationTwo Single Nucleotide Polymorphisms Identify the Highest-Risk Diabetes HLA Genotype
Barker, J. M., Triolo, T. M., Aly, T. A., Baschal, E. E., Babu, S. R., Kretowski, A. J., Rewers, M., & Eisenbarth, G. S. (2008) · Diabetes · doi:10.2337/db08-0605 · Cited by 65 · see citing works
Diagnosis, classification, and treatment of diabetes
Farmer, A. A., & Fox, R. A. (2011) · BMJ · doi:10.1136/bmj.d3319 · Cited by 42 · see citing works
Can genetic evidence help us understand why height and weight relate to social position?
Smith, G. D., & Davies, N. M. (2016) · BMJ · doi:10.1136/bmj.i1224 · Cited by 11 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
DiMeglio, L. A., Evans-Molina, C., & Oram, R. A. (2018) · The Lancet · doi:10.1016/s0140-6736(18)31320-5 · Cited by 1,561 · see citing works
Self-citationHolt, R. I. G., DeVries, J. H., Hess-Fischl, A., Hirsch, I. B., Kirkman, M. S., Klupa, T., Ludwig, B., Nørgaard, K., Pettus, J., Renard, E., et al. (2021) · Diabetes Care · doi:10.2337/dci21-0043 · Cited by 699 · see citing works
Responsible use of polygenic risk scores in the clinic: potential benefits, risks and gaps
Polygenic Risk Score Task Force of the International Common Disease Alliance, Adeyemo, A., Balaconis, M. K., Darnes, D. R., Fatumo, S., Granados Moreno, P., Hodonsky, C. J., Inouye, M., Kanai, M., Kato, K., et al. (2021) · Nature Medicine · doi:10.1038/s41591-021-01549-6 · Cited by 413 · see citing works
Chung, W. K., Erion, K., Florez, J. C., Hattersley, A. T., Hivert, M.-F., Lee, C. G., McCarthy, M. I., Nolan, J. J., Norris, J. M., Pearson, E. R., et al. (2020) · Diabetes Care · doi:10.2337/dci20-0022 · Cited by 400 · see citing works
Sharp, S. A., Rich, S. S., Wood, A. R., Jones, S. E., Beaumont, R. N., Harrison, J. W., Schneider, D. A., Locke, J. M., Tyrrell, J., Weedon, M. N., et al. (2019) · Diabetes Care · doi:10.2337/dc18-1785 · Cited by 366 · see citing works
Self-citationNew frontiers in the treatment of type 1 diabetes
Warshauer, J. T., Bluestone, J. A., & Anderson, M. S. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2019.11.017 · Cited by 259 · see citing works
13. Children and Adolescents: <i>Standards of Medical Care in Diabetes—2021</i>
American Diabetes Association (2021) · Diabetes Care · doi:10.2337/dc21-s013 · Cited by 223 · see citing works
Chung, W. K., Erion, K., Florez, J. C., Hattersley, A. T., Hivert, M.-F., Lee, C. G., McCarthy, M. I., Nolan, J. J., Norris, J. M., Pearson, E. R., et al. (2020) · Diabetologia · doi:10.1007/s00125-020-05181-w · Cited by 203 · see citing works
Self-citationThomas, N. J., Lynam, A. L., Hill, A. V., Weedon, M. N., Shields, B. M., Oram, R. A., McDonald, T. J., Hattersley, A. T., & Jones, A. G. (2019) · Diabetologia · doi:10.1007/s00125-019-4863-8 · Cited by 183 · see citing works
Insulin Therapy in Adults with Type 1 Diabetes Mellitus: a Narrative Review
Janež, A., Guja, C., Mitrakou, A., Lalic, N., Tankova, T., Czupryniak, L., Tabák, A. G., Prazny, M., Martinka, E., & Smircic-Duvnjak, L. (2020) · Diabetes Therapy · doi:10.1007/s13300-019-00743-7 · Cited by 177 · see citing works
Jones, A. G., McDonald, T. J., Shields, B. M., Hagopian, W., & Hattersley, A. T. (2021) · Diabetes Care · doi:10.2337/dc20-2834 · Cited by 122 · see citing works
Self-citationLynam, A., McDonald, T., Hill, A., Dennis, J., Oram, R., Pearson, E., Weedon, M., Hattersley, A., Owen, K., Shields, B., et al. (2019) · BMJ Open · doi:10.1136/bmjopen-2019-031586 · Cited by 72 · see citing works
Approaches and advances in the genetic causes of autoimmune disease and their implications
Inshaw, J. R. J., Cutler, A. J., Burren, O. S., Stefana, M. I., & Todd, J. A. (2018) · Nature Immunology · doi:10.1038/s41590-018-0129-8 · Cited by 70 · see citing works
Heerspink, H. J. L., Birkenfeld, A. L., Cherney, D. Z. I., Colhoun, H. M., Ji, L., Mathieu, C., Groop, P.-H., Pratley, R. E., Rosas, S. E., Rossing, P., et al. (2023) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2023.110908 · Cited by 63 · see citing works
Benton, M., Cleal, B., Prina, M., Baykoca, J., Willaing, I., Price, H., & Ismail, K. (2023) · General Hospital Psychiatry · doi:10.1016/j.genhosppsych.2022.11.004 · Cited by 58 · see citing works
WITHDRAWN: Reprint of: Classification of diabetes mellitus
Adler, A., Bennett, P., Chair, S. C., Gregg, E., Venkat Narayan, K. M., Schmidt, M. I., Sobngwi, E., Tajima, N., Tandon, N., Unwin, N., et al. (2021) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2021.108972 · Cited by 38 · see citing works
RetractedLawrence, J. M., Slezak, J. M., Quesenberry, C., Li, X., Yu, L., Rewers, M., Alexander, J. G., Takhar, H. S., Sridhar, S., Albright, A., et al. (2021) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2020.108624 · Cited by 34 · see citing works
Talbo, M. K., Katz, A., Dostie, M., Legault, L., & Brazeau, A.-S. (2022) · Canadian Journal of Diabetes · doi:10.1016/j.jcjd.2022.02.008 · Cited by 28 · see citing works
- Authors
- Thomas, N. J., Jones, S. E., Weedon, M. N., Shields, B. M., Oram, R. A., & Hattersley, A. T.
- Affiliations
- University of Exeter (GB)
- Corresponding author
- Hattersley, Andrew T
- ORCID
- Venue
- The Lancet Diabetes & Endocrinology
- Publisher
- Elsevier BV
- Published
- 2018-02
- Volume
- 6
- Issue
- 2
- Pages
- 122-129
- ISSN
- 2213-8587 (ISSN-L)
- PMC
- PMC5805861
- OpenAlex
- W2774874882
- Cited by
- 417
- References
- 27
- Citations by year
- 2026: 41 · 2025: 49 · 2024: 33 · 2023: 43 · 2022: 51 · 2021: 61 · 2020: 52 · 2019: 45 · 2018: 41 · 2017: 1
- FWCI
- 25.17
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- The Lancet Diabetes & Endocrinology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Open Research Exeter (University of Exeter) (publishedVersion, cc-by)
- Figshare (submittedVersion)
- Royal Devon and Exeter Research Repository (Royal Devon and Exeter) (submittedVersion, cc-by)
- Funders
- Wellcome Trust (098395/Z/12/Z)
- National Institute for Health and Care Research (CL-2015-23-001, NF-SI-0611-10219, NF-SI-0616-10080)
- Medical Research Council (MC_PC_15047)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- type 1 diabetes, adult-onset type 1 diabetes, genetic susceptibility, polygenic risk score, type 2 diabetes, age at diagnosis, clinical phenotype, body mass index, insulin use, UK Biobank, survival analysis, genetic stratification
- MeSH terms
- Adult, Aged, Cross-Sectional Studies, Diabetes Mellitus, Type 1, Female, Genotype, United Kingdom, Humans, Male, Middle Aged, Phenotype, Time Factors, Prevalence, Survival Rate, Databases, Factual, Biological Specimen Banks, Genetic Predisposition to Disease
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
