Plasma Adrenomedullin, Allelic Variations in the ADM Gene, and Risk for Lower-Limb Amputation in People With Type 2 Diabetes. - Biology of Cardiovascular Diseases Accéder directement au contenu
Article Dans Une Revue Diabetes Care Année : 2022

Plasma Adrenomedullin, Allelic Variations in the ADM Gene, and Risk for Lower-Limb Amputation in People With Type 2 Diabetes.

Résumé

Patients with diabetes have an increased risk for lower-limb amputation (LLA), but biomarkers to assess risk of LLA are lacking. Adrenomedullin (ADM) is a vasodilator peptide that also plays a role in fluid and electrolyte homeostasis in the kidney, increasing natriuresis and diuresis. ADM was shown to be associated with cardiovascular and renal events in diabetes, but it was not investigated in terms of LLA risk. We investigated the hypothesis that ADM is associated with LLA in people with type 2 diabetes. We studied 4,375 participants in the DIABHYCAR and SURDIAGENE cohorts (men, 68%; mean 66 years of age; mean duration of diabetes 12 years; and median follow-up 5.3 years). Plasma midregional proadrenomedullin (MR-proADM; a surrogate for ADM) was measured by immunofluorescence. Five single nucleotide polymorphisms (SNPs) in the ADM gene region were genotyped. LLA requirement during follow-up by increasing tertiles of plasma MR-proADM distribution was 1.0% (tertile 1 [T1]), 2.3% (T2), and 4.4% (T3) (P < 0.0001). In Cox multivariate analysis, the adjusted hazard ratio (95% CI) for LLA was 4.40 (2.30-8.88) (P < 0.0001) for T3 versus T1. Moreover, MR-proADM significantly improved indices for risk stratification of LLA. Four SNPs were associated with plasma MR-proADM concentration at baseline and with LLA during follow-up. Alleles associated with higher MR-proADM were associated with increased LLA risk. We observed associations of plasma MR-proADM with LLA and of ADM SNPs with plasma MR-proADM and with LLA in people with type 2 diabetes. This pattern of Mendelian randomization supports the causality of the association of ADM with LLA.

Dates et versions

hal-03722093 , version 1 (13-07-2022)

Identifiants

Citer

Louis Potier, Kamel Mohammedi, Pierre-Jean Saulnier, Frédéric Fumeron, Jean-Michel Halimi, et al.. Plasma Adrenomedullin, Allelic Variations in the ADM Gene, and Risk for Lower-Limb Amputation in People With Type 2 Diabetes.. Diabetes Care, 2022, 45 (7), pp.1631-1639. ⟨10.2337/dc21-2638⟩. ⟨hal-03722093⟩
14 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More