Background: Nontraumatic lower-limb amputation (LLA) and cardiovascular disease (CVD) both result in reduced life expectancy in patients with type 1 diabetes, but the differential burden between these conditions is unknown. We compared the effects of LLA and CVD on the risk of all-cause death in people with type 1 diabetes.

Methods: We used pooled data from the SURGENE, GENEDIAB, and GENESIS prospective cohorts. Data were divided into: 1) absence of CVD (myocardial infarction and/or stroke) nor LLA, 2) history of CVD alone without LLA, 3) LLA alone without CVD or 4) CVD and LLA at baseline. Participants with baseline history of peripheral artery disease were excluded from groups 1 and 2. The study endpoint was all-cause death.

Results: Among 1169 (male 55%, age 40 ± 13 years, diabetes duration 23 ± years) participants, LLA, CVD or 2 combined conditions were present at baseline in 62 (5.3%) , 49 (4.2%) and 20 (1.7%) subjects, respectively. All-cause death occurred in 3 (26%) subjects during 17-year follow-up. The risk of all-cause death increased in subjects withbaseline history of LLA (adjusted HR 2.26 [95% CI, 1.56 - 3.28], p<0.0001) or CVD (2.00 [1.34 - 3.01], p=0.0008) versus no condition, with an additive effect in those with two combined conditions (5.32 [3.14 - 9.00], p<0.0001) . No incremental risk of death was observed in people with CVD versus LLA (0.87 [0.54 - 1.41]) . Compared with no condition, LLA and CVD were similarly associated with reduced life expectancy during follow-up: 3.38 (95% CI, 1.87 -4.88) and 2.79 (1.26 - 4.32) years, respectively. Combined conditions expose to 7. (4.76 - 9.31) less years of life expectancy (all p<0.0001) .

Conclusion: LLA and CVD conferred a similar and heavy burden regarding mortality in type 1 diabetes population. Our findings encourage a careful consideration of people with type 1 diabetes and LLA as it is usually done for those with CVD, in terms of management of risk factors, treatments and prevention.


M.Camoin: None. O.Bourron: Other Relationship; Novo Nordisk. A.Scheen: Advisory Panel; AstraZeneca, Eli Lilly and Company, Merck Sharp & Dohme Corp., Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk. R.Roussel: None. M.Marre: Board Member; AstraZeneca, Consultant; Novo Nordisk. K.Mohammedi: Board Member; Lilly, Novo Nordisk, Sanofi, Research Support; Cyclerion Therapeutics, Inc., Speaker's Bureau; Abbott, AstraZeneca. G.Velho: None. P.Saulnier: Consultant; Grünenthal Group, Research Support; AstraZeneca, Novo Nordisk, Sanofi. L.Potier: Board Member; Boehringer Ingelheim International GmbH, Lilly, Novo Nordisk, Consultant; AstraZeneca, Sanofi. Y.Abouleka: None. C.Carpentier: None. S.Dubois: None. A.Larroumet: Consultant; Lilly Diabetes, Novo Nordisk, Sanofi. V.Rigalleau: None.

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