Araz Rawshani1, Naveed Sattar2, Stefan Franzén3, Aidin Rawshani4, Andrew T Hattersley5, Ann-Marie Svensson3, Björn Eliasson6, Soffia Gudbjörnsdottir7. 1. Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden. Electronic address: araz.rawshani@gu.se. 2. Institute of Cardiovascular and Medical Sciences, University of Glasgow, UK. Electronic address: naveed.sattar@glasgow.ac.uk. 3. The Swedish National Diabetes Register, Västra Götalandsregionen, Gothenburg, Sweden. 4. The Sahlgrenska University Hospital, Gothenburg, Sweden. 5. Institute of Biomedical & Clinical Science, University of Exeter Medical School, Exeter, UK. 6. Department of Internal Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden. 7. Institute of Cardiovascular and Medical Sciences, University of Glasgow, UK; The Swedish National Diabetes Register, Västra Götalandsregionen, Gothenburg, Sweden.
Abstract
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.
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.
Authors: Aidin Rawshani; Araz Rawshani; Stefan Franzén; Björn Eliasson; Ann-Marie Svensson; Mervete Miftaraj; Darren K McGuire; Naveed Sattar; Annika Rosengren; Soffia Gudbjörnsdottir Journal: N Engl J Med Date: 2017-04-13 Impact factor: 91.245
Authors: Sarah D de Ferranti; Ian H de Boer; Vivian Fonseca; Caroline S Fox; Sherita Hill Golden; Carl J Lavie; Sheela N Magge; Nikolaus Marx; Darren K McGuire; Trevor J Orchard; Bernard Zinman; Robert H Eckel Journal: Circulation Date: 2014-08-11 Impact factor: 29.690
Authors: Eileen Morgan; Catherine R Black; Noina Abid; Christopher R Cardwell; David R McCance; Christopher C Patterson Journal: Pediatr Diabetes Date: 2017-05-26 Impact factor: 4.866
Authors: Ian Ford; Heather Murray; Chris J Packard; James Shepherd; Peter W Macfarlane; Stuart M Cobbe Journal: N Engl J Med Date: 2007-10-11 Impact factor: 91.245
Authors: Michael J Haller; Jennifer M Stein; Jonathan J Shuster; Douglas Theriaque; Margaret M Samyn; Carl Pepine; Janet H Silverstein Journal: J Pediatr Endocrinol Metab Date: 2009-01 Impact factor: 1.634
Authors: Shona J Livingstone; Daniel Levin; Helen C Looker; Robert S Lindsay; Sarah H Wild; Nicola Joss; Graham Leese; Peter Leslie; Rory J McCrimmon; Wendy Metcalfe; John A McKnight; Andrew D Morris; Donald W M Pearson; John R Petrie; Sam Philip; Naveed A Sattar; Jamie P Traynor; Helen M Colhoun Journal: JAMA Date: 2015-01-06 Impact factor: 56.272
Authors: Børge G Nordestgaard; M John Chapman; Steve E Humphries; Henry N Ginsberg; Luis Masana; Olivier S Descamps; Olov Wiklund; Robert A Hegele; Frederick J Raal; Joep C Defesche; Albert Wiegman; Raul D Santos; Gerald F Watts; Klaus G Parhofer; G Kees Hovingh; Petri T Kovanen; Catherine Boileau; Maurizio Averna; Jan Borén; Eric Bruckert; Alberico L Catapano; Jan Albert Kuivenhoven; Päivi Pajukanta; Kausik Ray; Anton F H Stalenhoef; Erik Stroes; Marja-Riitta Taskinen; Anne Tybjærg-Hansen Journal: Eur Heart J Date: 2013-08-15 Impact factor: 29.983
Authors: Jamie R J Inshaw; Antony J Cutler; Daniel J M Crouch; Linda S Wicker; John A Todd Journal: Diabetes Care Date: 2019-09-26 Impact factor: 19.112
Authors: Kevan C Herold; Brian N Bundy; S Alice Long; Jeffrey A Bluestone; Linda A DiMeglio; Matthew J Dufort; Stephen E Gitelman; Peter A Gottlieb; Jeffrey P Krischer; Peter S Linsley; Jennifer B Marks; Wayne Moore; Antoinette Moran; Henry Rodriguez; William E Russell; Desmond Schatz; Jay S Skyler; Eva Tsalikian; Diane K Wherrett; Anette-Gabriele Ziegler; Carla J Greenbaum Journal: N Engl J Med Date: 2019-06-09 Impact factor: 91.245
Authors: Kevan C Herold; Jesse Reynolds; James Dziura; David Baidal; Jason Gaglia; Stephen E Gitelman; Peter A Gottlieb; Jennifer Marks; Louis H Philipson; Rodica Pop-Busui; Ruth S Weinstock Journal: Diabetes Obes Metab Date: 2020-07-29 Impact factor: 6.577
Authors: Pattara Wiromrat; Petter Bjornstad; Carissa Vinovskis; Linh T Chung; Carlos Roncal; Laura Pyle; Miguel A Lanaspa; Richard J Johnson; David Z Cherney; Tyler K Reznick-Lipina; Franziska Bishop; David M Maahs; Raj Paul Wadwa Journal: Pediatr Diabetes Date: 2019-08-29 Impact factor: 4.866