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Excess mortality and cardiovascular disease in young adults with type 1 diabetes in relation to age at onset: a nationwide, register-based cohort study
Open accessAbstract
Background People with type 1 diabetes are at elevated risk of mortality and cardiovascular disease, yet current guidelines do not consider age of onset as an important risk stratifier. We aimed to examine how age at diagnosis of type 1 diabetes relates to excess mortality and cardiovascular risk.Methods We did a nationwide, register-based cohort study of individuals with type 1 diabetes in the Swedish National Diabetes Register and matched controls from the general population. We included patients with at least one registration between Jan 1, 1998, and Dec 31, 2012. Using Cox regression, and with adjustment for diabetes duration, we estimated the excess risk of all-cause mortality, cardiovascular mortality, non-cardiovascular mortality, acute myocardial infarction, stroke, cardiovascular disease (a composite of acute myocardial infarction and stroke), coronary heart disease, heart failure, and atrial fibrillation. Individuals with type 1 diabetes were categorised into five groups, according to age at diagnosis: 0-10 years, 11-15 years, 16-20 years, 21-25 years, and 26-30 years.Findings 27 195 individuals with type 1 diabetes and 135 178 matched controls were selected for this study. 959 individuals with type 1 diabetes and 1501 controls died during follow-up (median follow-up was 10 years). Patients who developed type 1 diabetes at 0-10 years of age had hazard ratios of 4·11 (95% CI 3·24-5·22) for all-cause mortality, 7·38 (3·65-14·94) for cardiovascular mortality, 3·96 (3·06-5·11) for non-cardiovascular mortality, 11·44 (7·95-16·44) for cardiovascular disease, 30·50 (19·98-46·57) for coronary heart disease, 30·95 (17·59-54·45) for acute myocardial infarction, 6·45 (4·04-10·31) for stroke, 12·90 (7·39-22·51) for heart failure, and 1·17 (0·62-2·20) for atrial fibrillation. Corresponding hazard ratios for individuals who developed type 1 diabetes aged 26-30 years were 2·83 (95% CI 2·38-3·37) for all-cause mortality, 3·64 (2·34-5·66) for cardiovascular mortality, 2·78 (2·29-3·38) for non-cardiovascular mortality, 3·85 (3·05-4·87) for cardiovascular disease, 6·08 (4·71-7·84) for coronary heart disease, 5·77 (4·08-8·16) for acute myocardial infarction, 3·22 (2·35-4·42) for stroke, 5·07 (3·55-7·22) for heart failure, and 1·18 (0·79-1·77) for atrial fibrillation; hence the excess risk differed by up to five times across the diagnosis age groups. The highest overall incidence rate, noted for all-cause mortality, was 1·9 (95% CI 1·71-2·11) per 100 000 person-years for people with type 1 diabetes. Development of type 1 diabetes before 10 years of age resulted in a loss of 17·7 life-years (95% CI 14·5-20·4) for women and 14·2 life-years (12·1-18·2) for men.Interpretation Age at onset of type 1 diabetes is an important determinant of survival, as well as all cardiovascular outcomes, with highest excess risk in women. Greater focus on cardioprotection might be warranted in people with early-onset type 1 diabetes.Funding Swedish Heart and Lung Foundation.
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“The risk of diabetesrelated complications also remains notably high for all people with type 1 diabetes.1,2”
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“life expectancy remains reduced for individuals diagnosed with type 1 diabetes before age 10 years compared with both people diagnosed after 10 years and people without type 1 diabetes.1,2”
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“A recent risk tool, developed based on the Scottish/Swedish Diabetes Registry and validated in the Swedish National Diabetes Register can provide individualized risk predictions.793”
From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [793]
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Taylor, P. N., Collins, K. S., Lam, A. P., Karpen, S. R., Greeno, B., Walker, F., Lozano, A., Atabakhsh, E., Ahmed, S. T., Marinac, M., et al. (2023) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(23)00267-x · Cited by 72
Knobler, R., Arenberger, P., Arun, A., Assaf, C., Bagot, M., Berlin, G., Bohbot, A., Calzavara‐Pinton, P., Child, F. J., Cho, A., et al. (2020) · Journal of the European Academy of Dermatology and Venereology · doi:10.1111/jdv.16889 · Cited by 63
IL-6 receptor blockade does not slow β cell loss in new-onset type 1 diabetes
Greenbaum, C. J., Serti, E., Lambert, K., Weiner, L. J., Kanaparthi, S., Lord, S. M., Gitelman, S. E., Wilson, D. M., Gaglia, J. L., Griffin, K., et al. (2021) · JCI Insight · doi:10.1172/jci.insight.150074 · Cited by 62
Pané, A., Conget, I., Boswell, L., Ruiz, S., Viñals, C., Perea, V., Giménez, M., Cofán, M., Blanco, J., Vinagre, I., et al. (2020) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.3323 · Cited by 60
“Due to the growing prevalence of obesity in T1D,(35) eGDR could emerge as a chief non-glycaemic variable for the early detection of patients in whom intensive treatment (either cardioprotective or glucose-lowering(7)) is warranted in order to tackle the main cause of mortality among this population.(1,3,6)”
BackgroundPleconaril and ribavirin in new-onset type 1 diabetes: a phase 2 randomized trial
Krogvold, L., Mynarek, I. M., Ponzi, E., Mørk, F. B., Hessel, T. W., Roald, T., Lindblom, N., Westman, J., Barker, P., Hyöty, H., et al. (2023) · Nature Medicine · doi:10.1038/s41591-023-02576-1 · Cited by 55
“Childhood-onset T1D is a severe disease not only because of disabling acute and late complications leading to shortened life expectancy, but also because of the heavy burden of a demanding therapy regimen on patients and their families 2 .”
BackgroundKariyawasam, D., Morin, C., Casteels, K., Tallec, C. L., Sfez, A., Godot, C., Huneker, E., Garrec, N., Benhamou, P., Polak, M., et al. (2022) · The Lancet Digital Health · doi:10.1016/s2589-7500(21)00271-5 · Cited by 61
Arffman, M., Hakkarainen, P., Keskimäki, I., Oksanen, T., & Sund, R. (2023) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2023.110580 · Cited by 58
Carlsson, P., Espes, D., Sisay, S., Davies, L. C., Rjh, S., & Svahn, M. G. (2023) · Diabetologia · doi:10.1007/s00125-023-05934-3 · Cited by 60
“Despite great advances in insulin formulations and medical technology devices, people living with type 1 diabetes still have an increased risk of complications and, dependent on age at diagnosis and sex, have a shortened life span by 10–18 years [5].”
BackgroundZimmermann, A., Lanzinger, S., Kummernes, S. J., Lund‐Blix, N. A., Holl, R. W., Fröhlich-Reiterer, E. E., Maahs, D. M., Ebekozien, O. A., Rompicherla, S., Warner, J., et al. (2024) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(24)00279-1 · Cited by 66
The Changing Epidemiology of Type 1 Diabetes: A Global Perspective
Bell, K. J., & Lain, S. J. (2025) · Diabetes Obesity and Metabolism · doi:10.1111/dom.16501 · Cited by 61
“97 However, the appropriate methodology for adjustment of the duration of diabetes within this study has been questioned, 98 and other studies have shown conflicting results.”
The Impact of Diabetes Mellitus on Cardiovascular Risk Onset in Children and Adolescents
Pastore, I., Bolla, A. M., Montefusco, L. B., Lunati, M. E., Rossi, A., Assi, E., Zuccotti, G., & Fiorina, P. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21144928 · Cited by 67
Huerta‐Uribe, N., Ramírez‐Vélez, R., Izquierdo, M., & García‐Hermoso, A. (2022) · Sports Medicine · doi:10.1007/s40279-022-01741-9 · Cited by 58
Chiesa, S. T., Charakida, M., McLoughlin, E., Nguyen, H. C., Georgiopoulos, G., Motran, L., Elia, Y., Marcovecchio, M. L., Dunger, D. B., Dalton, R. N., et al. (2019) · European Heart Journal · doi:10.1093/eurheartj/ehz114 · Cited by 54
Meta-analysis of type 1 diabetes mellitus and risk of cardiovascular disease
Cai, X., Li, J., Cai, W., Chen, C., Ma, J., Xie, Z., Dong, Y., Liu, C., Xue, R., & Zhao, J. (2021) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2020.107833 · Cited by 58
Fortin, A., RABASA-LHORET, R. P. R., Lemieux, S., Labonté, M., & Gingras, V. (2018) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2018.08.005 · Cited by 52
JENDLE, J. H., Pöhlmann, J., de Portu, S., Smith‐Palmer, J., & Roze, S. (2019) · Diabetes Technology & Therapeutics · doi:10.1089/dia.2018.0328 · Cited by 55
Shah, V. N., Bailey, R. J., Wu, M., Foster, N. C., Pop‐Busui, R., Katz, M. L., Crandall, J. P., Bacha, F. F., Nadeau, K. J., Libman, I. M., et al. (2020) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaa015 · Cited by 58
Ludvigsson, J., Sumnik, Z., Pelikanova, T., Nattero Chavez, L., Lundberg, E., Rica, I., Martínez-Brocca, M. A., Ruiz de Adana, M., Wahlberg, J., Katsarou, A., et al. (2021) · Diabetes Care · doi:10.2337/dc21-0318 · Cited by 58
“Many individuals with type 1 diabetes (T1D) have a long life, with reasonably good quality of life, but even with modern treatment, the disease still causes serious morbidity (1) and increased mortality (2,3).”
BackgroundBraffett, B. H., Bebu, I., ghormli, L. K. E., Cowie, C. C., Sivitz, W. I., Pop‐Busui, R., Larkin, M., Gubitosi‐Klug, R., Nathan, D. M., Lachin, J. M., et al. (2022) · JAMA Network Open · doi:10.1001/jamanetworkopen.2022.30710 · Cited by 53
“5 (3-9) years of follow-up, intensive therapy was found to markedly reduce the development and progression of complications.”
BackgroundRigby, M. R., Hayes, B. A., Li, Y., Vercruysse, F., Hedrick, J. A., & Quattrin, T. (2022) · Diabetes Care · doi:10.2337/dc22-0908 · Cited by 55
“In this era of medicine and health care and advances in diabetes management, those with T1D have twice the mortality than matched control subjects and have a life expectancy reduced by almost two decades (20,21).”
BackgroundDovč, K., Lanzinger, S., Cardona‐Hernandez, R., Tauschmann, M., Marigliano, M., Cherubini, V., Preikša, R. T., Schierloh, U. H. E., Clapin, H. F., Aljaser, F., et al. (2023) · JAMA Network Open · doi:10.1001/jamanetworkopen.2023.0077 · Cited by 49
Dejgaard, T. F., von Scholten, B. J., Christiansen, E., Kreiner, F. F., Bardtrum, L., von Herrath, M., Mathieu, C., Madsbad, S., & ADJUNCT ONE and ADJUNCT TWO Investigators (2021) · Diabetes Obesity and Metabolism · doi:10.1111/dom.14532 · Cited by 48
“In industrialized parts of the world, adults with type 1 diabetes are often overweight or obese, further complicating obtaining adequate glycaemic control and increasing the risk of cardiovascular complications, which is markedly elevated in type 1 diabetes.(3-6) In addition, evidence suggests that a high body mass in…”
BackgroundResultVascular Complication in Adolescents With Diabetes Mellitus
Graves, L. E., & Donaghue, K. C. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00370 · Cited by 52
“neuropathy and macrovascular disease (13, 21).”
BackgroundInfluentialTougaard, N. H., Theilade, S., Winther, S. A., Tofte, N., Ahluwalia, T. S., Hansen, T. W., Rossing, P. R., & Frimodt‐Møller, M. (2020) · Journal of the American Heart Association · doi:10.1161/jaha.120.017165 · Cited by 48
“22 The other end points were as follows: (1) progression from normoalbuminuria to microalbuminuria or macroalbuminuria or from microalbuminuria to macroalbuminuria; (2) decline in eGFR of minimum 30% from baseline; (3) ESKD (defined as chronic kidney disease [CKD] stage 5 (ICD-10 code N18.”
BackgroundArroyave, F., Montaño, D., & Lizcano, F. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21228685 · Cited by 52
Management of diabetes complications in youth
Graves, L. E., & Donaghue, K. C. (2019) · Therapeutic Advances in Endocrinology and Metabolism · doi:10.1177/2042018819863226 · Cited by 52
Excess Cardiovascular Risk in Type 1 Diabetes Mellitus
Petrie, J. R., & Sattar, N. A. (2019) · Circulation · doi:10.1161/circulationaha.118.038137 · Cited by 46
Self-citationBélteky, M., Milletich, P. L., Ahrens, A. P., Triplett, E. W., & Ludvigsson, J. (2023) · Diabetologia · doi:10.1007/s00125-023-05895-7 · Cited by 44
“Type 1 diabetes, a heterogeneous, serious autoimmune disease associated with high morbidity and a shorter life expectancy [1], is characterised by the destruction of the insulin-producing beta cells of the pancreas.”
BackgroundAtherosclerotic Cardiovascular Risk as an Emerging Priority in Pediatrics
Schipper, H. S., & de Ferranti, S. D. (2022) · PEDIATRICS · doi:10.1542/peds.2022-057956 · Cited by 48
Glucagon-like peptide-1 receptor agonists as add-on therapy to insulin for type 1 diabetes mellitus
Tan, X., Pan, X., Wu, X., Zheng, S., Chen, Y., Liu, D., & Zhang, X. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.975880 · Cited by 44
The double burden: type 1 diabetes and heart failure—a comprehensive review
Julián, M. T., de, A. P.-M., Julve, J., & Alonso, N. (2024) · Cardiovascular Diabetology · doi:10.1186/s12933-024-02136-y · Cited by 52
“The study underscores the substantial impact of age at T1D onset on mortality and cardio-vascular risks [26].”
BackgroundThe future of type 1 diabetes therapy
Ziegler, A.-G., Cengiz, E., & Kay, T. W. H. (2025) · The Lancet · doi:10.1016/s0140-6736(25)01438-2 · Cited by 42
Do sex differences in paediatric type 1 diabetes care exist? A systematic review
de Vries, S. A. G., Verheugt, C. L., Mul, D., Nieuwdorp, M., & Sas, T. (2023) · Diabetologia · doi:10.1007/s00125-022-05866-4 · Cited by 41
Svane, J., Lynge, T. H., Pedersen‐Bjergaard, U., Jespersen, T., Gislason, G., Risgaard, B., Winkel, B. G., & Tfelt‐Hansen, J. (2019) · European Journal of Preventive Cardiology · doi:10.1177/2047487319836550 · Cited by 42
Sex differences in the association of risk factors for heart failure incidence and mortality
Sillars, A., Ho, F. K. W., Pell, G. P., Gill, J. M. R., Sattar, N. A., Gray, S. R., & Celis-Morales, C. A. (2019) · Heart · doi:10.1136/heartjnl-2019-314878 · Cited by 44
“It is also notable that others have shown sex differences in the associations of T2DM with CVD in general [23] with emerging evidence for T1DM [24], lending external validity to our findings.”
ResultSelf-citationLittmann, K., Wodaje, T., Alvarsson, M., Bottai, M., Eriksson, M., Parini, P., & Brinck, J. W. (2019) · Diabetes Care · doi:10.2337/dc19-1398 · Cited by 41
“Young adults with type 1 diabetes still experience an increased vascular morbidity and mortality rate despite an improved vigilance in CVD risk factor management in clinical practice over the years (16).”
BackgroundEmirates Diabetes Society Consensus Guidelines for the Management of Type 2 Diabetes Mellitus – 2020
Alawadi, F., Abusnana, S., Afandi, B. O., Aldahmani, K. M., Hajeri, O. M. A., Aljaberi, K., Alkaabi, J., Al-Madani, A., Bashier, A. M., Beshyah, S., et al. (2020) · Dubai Diabetes and Endocrinology Journal · doi:10.1159/000506508 · Cited by 43
Herold, K. C., Reynolds, J., Dziura, J. D., Baidal, D. A., Gaglia, J. L., Gitelman, S. E., Gottlieb, P. A., Marks, J., Philipson, L. H., Pop‐Busui, R., et al. (2020) · Diabetes Obesity and Metabolism · doi:10.1111/dom.14121 · Cited by 44
Type 1 Diabetes and the HLA Region: Genetic Association Besides Classical HLA Class II Genes
Sticht, J., Álvaro‐Benito, M., & Konigorski, S. (2021) · Frontiers in Genetics · doi:10.3389/fgene.2021.683946 · Cited by 46
Teplizumab in Type 1 Diabetes Mellitus: An Updated Review
Thakkar, S., Chopra, A., Nagendra, L., Kalra, S., & Bhattacharya, S. (2023) · touchREVIEWS in Endocrinology · doi:10.17925/ee.2023.19.2.7 · Cited by 49
“19 As a result, clinical trials targeting innate and adaptative immunity (both T and B cells) to modify the natural course of T1DM have continued to garner attention.”
BackgroundAge of onset of diabetes and all-cause mortality
Ang, G. Y. (2020) · World Journal of Diabetes · doi:10.4239/wjd.v11.i4.95 · Cited by 41
Practical implementation of automated closed-loop insulin delivery: A French position statement
Tubiana‐Rufi, N., Schaepelynck, P., Franc, S., Chaillous, L., Joubert, M., Renard, É., Reznik, Y., Abettan, C., Bismuth, É., Beltrand, J., et al. (2020) · Diabetes & Metabolism · doi:10.1016/j.diabet.2020.10.004 · Cited by 42
Karamanakos, G., Kokkinos, A. D., Dalamaga, Μ., & Liatis, S. (2022) · Current Obesity Reports · doi:10.1007/s13679-022-00477-x · Cited by 44
Metadata
- Authors
- Rawshani, A., Sattar, N., Franzén, S., Rawshani, A., Hattersley, A. T., Svensson, A.-M., Eliasson, B., & Gudbjörnsdottir, S.
- Affiliations
- Sahlgrenska University Hospital (SE)
- University of Glasgow (GB)
- Region Västra Götaland (SE)
- University of Exeter (GB)
- University of Gothenburg (SE)
- Corresponding author
- Rawshani, Araz
- Sattar, Naveed
- ORCID
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2018-08
- Volume
- 392
- Issue
- 10146
- Pages
- 477-486
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- PMC
- PMC6828554
- OpenAlex
- W2887373570
- Cited by
- 802
- References
- 40
- Citations by year
- 2026: 81 · 2025: 103 · 2024: 113 · 2023: 108 · 2022: 101 · 2021: 114 · 2020: 105 · 2019: 67 · 2018: 9
- FWCI
- 58.64
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- The Lancet (publishedVersion)
- PubMed (publishedVersion)
- Open Research Exeter (University of Exeter) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (acceptedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion, cc-by-sa)
- Figshare (submittedVersion)
- Royal Devon and Exeter Research Repository (Royal Devon and Exeter) (submittedVersion)
- Funders
- Hjärt-Lungfonden
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Keywords
- type 1 diabetes, age at diagnosis, excess mortality, cardiovascular disease, cardiovascular mortality, coronary artery disease, heart failure, atrial fibrillation, acute myocardial infarction, stroke, young adults, risk stratification, diabetes duration, non-cardiovascular mortality, Swedish National Diabetes Register, sex differences in mortality
- MeSH terms
- Adolescent, Adult, Age Factors, Cardiovascular Diseases, Child, Child, Preschool, Diabetes Mellitus, Type 1, Female, Humans, Infant, Infant, Newborn, Male, Registries, Sweden, Cohort Studies, Proportional Hazards Models, Age of Onset, Diabetes Complications, Young Adult
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