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Diabetes Care. 2018 Oct;41(10):2162-2169. doi: 10.2337/dc18-0695. Epub 2018 Aug 2.

Prognostic Values of Inflammatory and Redox Status Biomarkers on the Risk of Major Lower-Extremity Artery Disease in Individuals With Type 2 Diabetes.

Nativel M1, Schneider F2,3, Saulnier PJ3,4,5, Gand E6, Ragot S3,4,5, Meilhac O7,8, Rondeau P7, Burillo E7, Cournot M7,9, Potier L10,11,12, Velho G12, Marre M10,11,12, Roussel R10,11,12, Rigalleau V1,13,14, Mohammedi K15,13,14, Hadjadj S3,5,16,17.

Author information

1
Département d'Endocrinologie, Diabétologie, Nutrition, Hôpital Haut-Lévêque, Pessac, Bordeaux, France.
2
Département de Chirurgie Vasculaire, CHU de Poitiers, Poitiers, France.
3
UFR de Médecine et Pharmacie, Université de Poitiers, Poitiers, France.
4
Centre d'Investigation Clinique, CHU de Poitiers, Poitiers, France.
5
CIC 1402, INSERM, Poitiers, France.
6
Pôle Dune, CHU de Poitiers, Poitiers, France.
7
UMR 1188 Diabète athérothrombose Thérapies Réunion Océan Indien (DéTROI), INSERM, Université de La Réunion, Saint Denis de La Réunion, France.
8
CHU de La Réunion, Saint Denis de La Réunion, France.
9
Service de cardiologie, Centre Hospitalier Gabriel Martin, Saint-Paul, France.
10
DHU FIRE, Département d'Endocrinologie, Diabétologie, Nutrition, Assistance Publique Hôpitaux de Paris, Bichat Hospital, Paris, France.
11
UFR de Médecine, Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
12
UMRS 1138, Centre de Recherche des Cordeliers, INSERM, Paris, France.
13
Faculté de Médecine, Université de Bordeaux, Bordeaux, France.
14
Centre de Recherche INSERM-Université de Bordeaux U1219 "Bordeaux Population Health," Bordeaux, France.
15
Département d'Endocrinologie, Diabétologie, Nutrition, Hôpital Haut-Lévêque, Pessac, Bordeaux, France km.mmohammedi@gmail.com.
16
Département d'Endocrinologie, Diabétologie, Nutrition, CHU de Poitiers, Poitiers, France.
17
Research Unit 1082, INSERM, Poitiers, France.

Abstract

OBJECTIVE:

Inflammation and oxidative stress play an important role in the pathogenesis of lower-extremity artery disease (LEAD). We assessed the prognostic values of inflammatory and redox status biomarkers on the risk of LEAD in individuals with type 2 diabetes.

RESEARCH DESIGN AND METHODS:

Plasma concentrations of tumor necrosis factor-α receptor 1 (TNFR1), angiopoietin-like 2, ischemia-modified albumin (IMA), fluorescent advanced glycation end products, protein carbonyls, and total reductive capacity of plasma were measured at baseline in the SURDIAGENE (Survie, Diabete de type 2 et Genetique) cohort. Major LEAD was defined as the occurrence during follow-up of peripheral revascularization or lower-limb amputation.

RESULTS:

Among 1,412 participants at baseline (men 58.2%, mean [SD] age 64.7 [10.6] years), 112 (7.9%) developed major LEAD during 5.6 years of follow-up. High plasma concentrations of TNFR1 (hazard ratio [95% CI] for second vs. first tertile 1.12 [0.62-2.03; P = 0.71] and third vs. first tertile 2.16 [1.19-3.92; P = 0.01]) and of IMA (2.42 [1.38-4.23; P = 0.002] and 2.04 [1.17-3.57; P = 0.01], respectively) were independently associated with an increased risk of major LEAD. Plasma concentrations of TNFR1 but not IMA yielded incremental information, over traditional risk factors, for the risk of major LEAD as follows: C-statistic change (0.036 [95% CI 0.013-0.059]; P = 0.002), integrated discrimination improvement (0.012 [0.005-0.022]; P < 0.001), continuous net reclassification improvement (NRI) (0.583 [0.294-0.847]; P < 0.001), and categorical NRI (0.171 [0.027-0.317]; P = 0.02).

CONCLUSIONS:

Independent associations exist between high plasma TNFR1 or IMA concentrations and increased 5.6-year risk of major LEAD in people with type 2 diabetes. TNFR1 allows incremental prognostic information, suggesting its use as a biomarker for LEAD.

PMID:
30072406
DOI:
10.2337/dc18-0695
[Indexed for MEDLINE]

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