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. 2022 May 9;21(1):71.
doi: 10.1186/s12933-022-01487-8.

Differential prognostic burden of cardiovascular disease and lower-limb amputation on the risk of all-cause death in people with long-standing type 1 diabetes

Marion Camoin  1   2 , Gilberto Velho  3 , Pierre-Jean Saulnier  4   5   6 , Louis Potier  2   3 , Yawa Abouleka  2 , Charlyne Carpentier  7 , Severine Dubois  7 , Alice Larroumet  1 , Vincent Rigalleau  1   8   9 , Elise Gand  5 , Olivier Bourron  10   11 , Lyse Bordier  12 , André Scheen  13 , Samy Hadjadj  14 , Ronan Roussel  2   3 , Michel Marre  3   15 , Kamel Mohammedi  16   17   18
Affiliations

Differential prognostic burden of cardiovascular disease and lower-limb amputation on the risk of all-cause death in people with long-standing type 1 diabetes

Marion Camoin et al. Cardiovasc Diabetol. .

Abstract

Background: Cardiovascular disease (CVD) and nontraumatic lower-limb amputation (LLA) each results in reduced life expectancy in patients with type 1 diabetes, but the differential burden between these conditions is unknown. We compared the effects of CVD and LLA on the risk of mortality 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/both conditions at baseline. Participants with baseline history of peripheral artery disease were excluded from groups 1 and 2. The study endpoint was any death occurring during follow-up, regardless of the causes.

Results: Among 1169 participants (male 55%, age 40 ± 13 years, diabetes duration 23 ± 11 years), CVD, LLA or both were present at baseline in 49 (4.2%), 62 (5.3%) and 20 (1.7%) subjects, respectively. All-cause death occurred in 304 (26%) participants during 17-year follow-up, corresponding to 18,426 person-years and an incidence rate of 16 (95%CI, 15-18) per 1000 person-years. The risk of death increased in individuals with baseline history of CVD (adjusted HR 2.00 [95% CI 1.34-3.01], p = 0.0008) or LLA (2.26 [1.56-3.28], p < 0.0001), versus no condition, with an additive effect in people with both 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, CVD and LLA were similarly associated with reduced life expectancy during follow-up: 2.79 (95% CI 1.26-4.32) and 3.38 (1.87-4.88) years, respectively. Combined conditions expose to 7.04 (4.76-9.31) less years of life expectancy (all p < 0.0001).

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

Keywords: Cardiovascular disease; Lower-limb amputation; Mortality; Myocardial infarction; Stroke; Type 1 diabetes mellitus.

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Conflict of interest statement

L.P. reports personal fees and non-financial support from Sanofi, Novo Nordisk, Eli Lilly and MSD. VR had grants from the Servier Diabetes institute, Roche, and Merck Lipha Santé. O.B. reports personal fees and non-financial support from MSD and Sanofi. L.B. reports personal fees and non-financial support from Astra Zeneca, Bayer, BD, BMS, Boerhinger Ingelheim, MSD, Novartis, Lilly, Novo Nordisk, Roche, and Sanofi. AS has received lecturer/advisor fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck Sharp and Dohme, Novartis, NovoNordisk, Sanofi and Servier. SH reports personal fees and non-financial support from Astra Zeneca, grants and personal fees from Bayer, personal fees from Boehringer Ingelheim, grants from Dinno Santé, personal fees from Eli Lilly, non-financial support from LVL, personal fees and non-financial support from MSD, personal fees from Novartis, grants from Pierre Fabre Santé, personal fees and non-financial support from Sanofi, personal fees and non-financial support from Servier, personal fees from Valbiotis. RR reports research grants from Sanofi, Novo Nordisk, and Diabnext, consulting and speakers’ bureau fees (compensation donated to the nonprofit Foundation APHP for Research) from Sanofi, Novo Nordisk, Eli Lilly, Boehringer-Ingelheim, Mundipharma, Janssen, AstraZeneca, MSD, Medtronic, and Abbott. MM is a consultant for Novo-Nordisk Algerian subsidiary, and has received personal fees from Novo-Nordisk, Merck-Sharp and Dohme, and Eli Lilly. KM reports personal fees or non-financial support from Novo Nordisk, Sanofi, Astra-Zeneca, Eli Lilly, Abbott, Boehringer-Ingelheim and LifeScan. Authors declare no other potential conflict of interest relevant to this article.

Figures

Fig. 1
Fig. 1
Kaplan Meier curves estimating the survival according to baseline history of cardiovascular disease (CVD) and lower-limb amputation (LLA): absent (green line), CVD only (red line), LLA only (blue line), and both CVD and LLA (black line). P < 0.0001
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