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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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“Despite the introduction of advanced technologies for diabetes management, individuals with T1D may experience a reduced life expectancy; consequently, researchers continue to seek methods not only to prevent T1D, but also to halt progression or even reverse the disease [10].”
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Self-citationLong-term complications of type 1 diabetes: what do we know and what do we need to understand?
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“However, and despite significant improvements in cardiovascular morbidity and mortality [8], patients with T1D are still exposed to significant excess mortality compared to people without diabetes [13].”
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“An important determining factor for survival is the age at onset of the disease.(7)”
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Cardiovascular risk management in type 1 diabetes
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“Considering the relatively early onset of T1D patients compared to T2D patients, development of CVD in T1D patients leads to more life-years lost [26].”
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“Clinical observational studies have suggested an association between diabetes mellitus and HF [21, 44–46].”
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“…National Diabetes Registry and 135,178 matched controls showed how patients with an early onset of T1D (age years) had a greater risk of suffering from HF (HR 12.9 95% CI compared to that of population without diabetes) than patients who develop T1D at a more advanced age ( 5.07 95% CI) [33].”
BackgroundInfluentialQu, Q., Guo, Q., Shi, J., Chen, Z., Sun, J.-Y., Cheang, I., Gao, R., Zhou, Y., Zhang, H., Liao, S., et al. (2024) · BMC Medicine · doi:10.1186/s12916-024-03453-5 · Cited by 18
Amor, A. J., Ortega, E., Giménez, M., Cofán, M., Blanco, J., Pané, A., Boswell, L., Vinagre, I., Esmatjes, E., & Conget, I. (2019) · Endocrinología Diabetes y Nutrición · doi:10.1016/j.endinu.2019.02.004 · Cited by 17
Bächle, C., Hoyer, A., Stahl‐Pehe, A., Castillo, K., Toennies, T., Lindner, L. M. E., Reinauer, C., Holl, R. W., Kuß, O., & Rosenbauer, J. (2019) · Journal of Adolescent Health · doi:10.1016/j.jadohealth.2019.05.016 · Cited by 15
Kordonouri, O., Lange, K., Biester, T., Datz, N., Kapitzke, K., Berge, T. V. D., Weiskorn, J., & Danne, T. (2019) · Diabetic Medicine · doi:10.1111/dme.14130 · Cited by 15
Cano, A., Llauradó, G., Albert, L., Mazarico, I., Astiarraga, B., González-Sastre, M., Martínez, L., Fernández‐Veledo, S., Simó, R., Vendrell, J. J., et al. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9072192 · Cited by 15
Glycemic control and complications of type 1 diabetes among children in Tanzania
Najem, S., Majaliwa, E. S., Ramaiya, K. L., Swai, A. B. M., Jasem, D., & Ludvigsson, J. (2020) · Journal of Clinical & Translational Endocrinology · doi:10.1016/j.jcte.2020.100245 · Cited by 15
“The risk of certain cardiovascular events among patients who got T1D at <10 years of age are up to 30 times higher than for controls [6].”
BackgroundInfluentialKiss, Z., Rokszin, G., Abonyi‐Tóth, Z., Jermendy, G., Kempler, P., Barkai, L., & Wittmann, I. (2019) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.3190 · Cited by 16
DPARD: rationale, design and initial results from the Dutch national diabetes registry
Bak, J. C. G., Mul, D., Serné, E. H., de Valk, H. W., Sas, T., Geelhoed-Duijvestijn, P. H. L. M., Kramer, M. H. H., Nieuwdorp, M., & Verheugt, C. L. (2021) · BMC Endocrine Disorders · doi:10.1186/s12902-021-00782-x · Cited by 15
Comorbidities in Recent-Onset Adult Type 1 Diabetes: A Comparison of German Cohorts
Zaharia, O., Lanzinger, S., Rosenbauer, J., Karges, W., Müssig, K., Meyhöfer, S. M., Burkart, V., Hummel, M., Raddatz, D., Roden, M., et al. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.760778 · Cited by 17
Li, G., Huang, K., Dong, G., Zhang, J., Gong, C., Luo, F., Luo, X., Wang, C., Zhu, M., Li, P., et al. (2022) · Frontiers in Pediatrics · doi:10.3389/fped.2022.888370 · Cited by 19
“The average life expectancy of children with T1DM is reduced by about 12 years even in western developed countries (10, 11).”
BackgroundJanssen, A. W. M., van Heck, J. I. P., Stienstra, R., Aarntzen, E. H. J. G., van Diepen, J. A., Riksen, N. P., & Tack, C. J. (2023) · Cardiovascular Research · doi:10.1093/cvr/cvad058 · Cited by 14
“Recent studies have confirmed the increased prevalence of CVD in T1D, which was particularly high in patients with young-onset disease, accounting for ∼15 years loss of life.(2) It is likely that this increased risk is related to the presence of chronic hyperglycaemia.”
BackgroundBuchmann, M., Tuncer, O., Auzanneau, M., Eckert, A. J., Rosenbauer, J., Reitzle, L., Heidemann, C., Holl, R. W., & Thamm, R. (2023) · PubMed Central · doi:10.25646/11439 · Cited by 18
Giménez‐Pérez, G., Viñals, C., Mata‐Cases, M., Vlacho, B., Real, J., Franch‐Nadal, J., Ortega, E., & Mauricio, D. (2023) · Cardiovascular Diabetology · doi:10.1186/s12933-023-01917-1 · Cited by 14
“Comparison with other studies is more difficult since, generally, peripheral artery disease [6] and in some cases also heart failure [23, 24], have not been included as outcomes when analysing the incidence and factors associated with CVD in patients with T1D.”
BackgroundResultSchnell, O., Valensi, P. E., Standl, E., & Ceriello, A. (2020) · Endocrinology Diabetes & Metabolism · doi:10.1002/edm2.129 · Cited by 15
Jia, L.-Y., Cao, G., Li, J., Gan, L., Li, J., Lan, X., Meng, Z., He, X. H., Zhang, C., Wang, C., et al. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.698981 · Cited by 14
Jahn, L. A., Logan, B. R., Love, K. M., Horton, W. B., Eichner, N. Z. M., Hartline, L. M., WELTMAN, A. L., & Barrett, E. J. (2021) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00267.2021 · Cited by 14
Survival of children and youth with type 1 diabetes mellitus in Tanzania
Majaliwa, E. S., Minja, L., Ndayongeje, J., Ramaiya, K. L., Mfinanga, S., & Mmbaga, B. T. (2022) · Pediatric Diabetes · doi:10.1111/pedi.13425 · Cited by 14
“This survey is contrary to the studies done in the developed world, whereby there is higher mortality in children diagnosed before the age of 10 years.(22,23)”
ResultBrinck, J. W., Hagström, E., Nåtman, J., Franzén, S., Eeg‐Olofsson, K., Nathanson, D., & Eliasson, B. (2022) · Diabetes Care · doi:10.2337/dc22-1025 · Cited by 14
“Cardiovascular disease is a leading cause of death for patients with type 1 and type 2 diabetes (2,21).”
BackgroundMethodSelf-citationThunander, M., Lindgren, A., Petersson, C., Landin‐Olsson, M., & Holmberg, S. (2019) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2019.107943 · Cited by 15
Basu, A., Chien, L.-C., Alman, A. C., & Snell‐Bergeon, J. K. (2021) · European Journal of Nutrition · doi:10.1007/s00394-021-02564-6 · Cited by 14
“People with type 1 diabetes (T1D) bear a higher burden of coronary artery disease (CAD) and subsequent cardiovascular mortality in comparison to those without diabetes [1, 2].”
BackgroundDyslipidaemia in Type 1 Diabetes: Molecular Mechanisms and Therapeutic Opportunities
O’Brien, S. T., Neylon, O. M., & O’Brien, T. (2021) · Biomedicines · doi:10.3390/biomedicines9070826 · Cited by 15
“CVD is the most common cause of death in Type 1 Diabetes (T1D) [1] and suboptimal glycaemic control is a significant risk factor for CVD [2].”
BackgroundKordonouri, O., Cuthbertson, D. D., Bélteky, M., Aschemeier, B., White, N. H., Cummings, E. A., Knip, M., & Ludvigsson, J. (2022) · Diabetologia · doi:10.1007/s00125-022-05786-3 · Cited by 16
Eliasson, B., Lyngfelt, L., Strömblad, S.-O., Franzén, S., & Eeg‐Olofsson, K. (2022) · Scientific Reports · doi:10.1038/s41598-022-22932-4 · Cited by 14
Self-citationTeixeira, P. F., Battelino, T., Carlsson, A., Guðbjörnsdóttir, S., Hannelius, U., von Herrath, M., Knip, M., Korsgren, O., Larsson, H. E., Lindqvist, A., et al. (2024) · Diabetologia · doi:10.1007/s00125-024-06089-5 · Cited by 16
“This is reflected in a loss of life expectancy at age 20 of approximately 12 years [6].”
BackgroundClosed-loop insulin delivery systems in children and adolescents with type 1 diabetes
Dovč, K., & Battelino, T. (2020) · Expert Opinion on Drug Delivery · doi:10.1080/17425247.2020.1713747 · Cited by 13
Armario, P., Brotons, C., Elosúa, R., de Leciñana, M. A., Castro, A., Clarà, A. B. I., Cortés, O., Rodríguez, Á. D., Herranz, M., Justo, S., et al. (2020) · Hipertensión y Riesgo Vascular · doi:10.1016/j.hipert.2020.07.004 · Cited by 13
Shear Stress and Metabolic Disorders—Two Sides of the Same Plaque
Jiang, M., Ding, H., Huang, Y., & Wang, L. (2021) · Antioxidants and Redox Signaling · doi:10.1089/ars.2021.0126 · Cited by 12
“A national registry study of type 1 diabetes in Sweden found that patients who developed type 1 diabetes by the age of 10 carried a 30-fold increased risk of CVD (145).”
Time trend in excess mortality in children with type 1 diabetes from 1987 to 2016 in mainland France
Donzeau, A., Piffaretti, C., Jossens, A., Levaillant, L., Bouhours‐Nouet, N., Amsellem‐Jager, J., Ghosn, W., Rey, G., Fosse‐Edorh, S., & Coutant, R. (2022) · Pediatric Diabetes · doi:10.1111/pedi.13298 · Cited by 15
“Achievement of near-normal blood glucose levels delayed the onset and progression of these morbidities and reduced long-term mortality,(1) although subjects with childhood-onset diabetes still have an excess long-term mortality.(2) Despite the improvements in care, diabetes-related mortality among those who developed…”
BackgroundAltered Taste Function in Young Individuals With Type 1 Diabetes
Catamo, E., Robino, A., Tinti, D., Dovč, K., Franceschi, R., Giangreco, M., Gasparini, P., Barbi, E., Cauvin, V., Rabbone, I., et al. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2021.797920 · Cited by 13
Tell, S. S., Schäfer, M., Vigers, T., Baumgartner, A., Lyon, E., Gross, S., Polsky, S., Snell‐Bergeon, J. K., Schauer, I. E., & Nadeau, K. J. (2022) · Diabetes Obesity and Metabolism · doi:10.1111/dom.14800 · Cited by 14
“People with type 1 diabetes are at significantly increased risk of morbidity and mortality from cardiovascular disease and diabetic kidney disease.(1,2) We and others have shown evidence of vascular and cardiac changes such as arterial stiffness, reduced arterial compliance, endothelial dysfunction, cardiac diastolic…”
BackgroundLan, N. S. R., Bell, D. A., Watts, G. F., & Fegan, P. G. (2022) · Current Opinion in Endocrinology Diabetes and Obesity · doi:10.1097/med.0000000000000790 · Cited by 13
“Owing to long duration of diabetes and early atherosclerosis, individuals diagnosed with T1D at younger ages are at increased ASCVD risk [2].”
Backgroundβ cell responses to inflammation
Usmani‐Brown, S., Perdigoto, A. L., Lavoie, N., Clark, P. L., Korah, M. M., Rui, J., Betancur, G., & Herold, K. C. (2019) · Molecular Metabolism · doi:10.1016/j.molmet.2019.06.013 · Cited by 14
“There has been progress in the management and prevention of secondary complications of the disease, but particularly for children who are diagnosed with T1D, there are ongoing risks of morbidity and loss of life-years [8,9].”
BackgroundMaurotti, S., Russo, C., Musolino, V., Nucera, S., Gliozzi, M., Scicchitano, M., Bosco, F., Morittu, V. M., Ragusa, M., Mazza, E., et al. (2020) · Calcified Tissue International · doi:10.1007/s00223-020-00716-0 · Cited by 13
“While new developments have been shown to improve acute life-threatening complications in patients with type 1 diabetes mellitus (T1DM) [1], long-term complications are still an ongoing burden for these patients [2].”
BackgroundPulkkinen, M., Tuomaala, A., Hero, M. T., Gordin, D., & Sarkola, T. (2020) · BMJ Open Diabetes Research & Care · doi:10.1136/bmjdrc-2020-001216 · Cited by 13
STOUGAARD, E. B., Andersen, M. R., Bagger, J. I., Søndergaard, E., Østergaard, J. A., Curovic, V. R., Persson, F., Almdal, T., Mathiesen, A. S., Andries, A., et al. (2025) · Diabetes Obesity and Metabolism · doi:10.1111/dom.16606 · Cited by 13
Kwiendacz, H., Wijata, A. M., Nalepa, J., Piaśnik, J., Kulpa, J., Herba, M., Boczek, S., Kegler, K., Hendel, M., Irlik, K., et al. (2023) · Cardiovascular Diabetology · doi:10.1186/s12933-023-01938-w · Cited by 14
“It is estimated that patients with DM and CVD and/or chronic kidney disease as well as those having at least three CVD risk factors or with DM duration over 20 years, are at a very high risk, with the 10-year risk of CVD death exceeding 10% [4].”
BackgroundHelmink, M. A. G., Hageman, S. H. J., Eliasson, B., Sattar, N. A., Visseren, F. L. J., Dorresteijn, J. A. N., Harris, K., Peters, S. A. E., Woodward, M., Szentkúti, P., et al. (2024) · Diabetes Obesity and Metabolism · doi:10.1111/dom.15531 · Cited by 15
Self-citationMajor adverse events in youth-onset type 1 and type 2 diabetes: The SEARCH and TODAY studies
Mottl, A. K., Tryggestad, J. B., Isom, S. P., Gubitosi‐Klug, R., Henkin, L. F., White, N. H., D'Agostino, R., Hughan, K. S., Dolan, L. M., & Drews, K. L. (2024) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2024.111606 · Cited by 13
Muñoz‐Pardeza, J., López‐Gil, J. F., Huerta‐Uribe, N., Hormazábal‐Aguayo, I., Izquierdo, M., & García‐Hermoso, A. (2024) · Cardiovascular Diabetology · doi:10.1186/s12933-024-02301-3 · Cited by 12
Patients with type 1 diabetes in a tertiary setting do not attain recommended lipid targets
Lan, N. S. R., Yeap, B. B., Bell, D. A., Watts, G. F., & Fegan, P. G. (2018) · Diabetes & Metabolism · doi:10.1016/j.diabet.2018.12.002 · Cited by 12
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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