• Louis Potier, Ronan Roussel, Michel Marre, Petter Bjornstad, David Z Cherney, Ray El Boustany, Frédéric Fumeron, Nicolas Venteclef, Jean-François Gautier, Samy Hadjadj, Kamel Mohammedi, and Gilberto Velho.
• Department of Diabetology, Endocrinology and Nutrition, DHU FIRE, Bichat Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France louis.potier@gmail.com.
• Diabetes Care. 2019 Dec 1; 42 (12): 2290-2297.

ObjectiveDiabetes is the leading cause of nontraumatic lower-extremity amputations (LEAs). Identification of patients with foot ulcers at risk for amputation remains clinically challenging. Plasma copeptin, a surrogate marker of vasopressin, is associated with the risk of cardiovascular and renal complications in diabetes.Research Design And MethodsWe assessed the association between baseline plasma copeptin and risk of LEA during follow-up in four cohorts of people with type 1 (GENESIS, n = 503, and GENEDIAB, n = 207) or type 2 diabetes (DIABHYCAR, n = 3,101, and SURDIAGENE, n = 1,452) with a median duration of follow-up between 5 and 10 years. Copeptin concentration was measured in baseline plasma samples by an immunoluminometric assay.ResultsIn the pooled cohorts with type 1 diabetes (n = 710), the cumulative incidence of LEA during follow-up by increasing tertiles (tertile 1 [TER1], TER2, and TER3) of baseline plasma copeptin was 3.9% (TER1), 3.3% (TER2), and 10.0% (TER3) (P = 0.002). Cox regression analyses confirmed the association of copeptin with LEA: hazard ratio (HR) for 1 SD increment of log[copeptin] was 1.89 (95% CI 1.28-2.82), P = 0.002. In the pooled cohorts of type 2 diabetes (n = 4,553), the cumulative incidence of LEA was 1.1% (TER1), 2.9% (TER2), and 3.6% (TER3) (P < 0.0001). In Cox regression analyses, baseline plasma copeptin was significantly associated with LEA: HR for 1 SD increment of log[copeptin] was 1.42 (1.15-1.74), P = 0.001. Similar results were observed in the cohort with type 2 diabetes for lower-limb revascularization (HR 1.20 [95% CI 1.03-1.39], P = 0.02).ConclusionsBaseline plasma copeptin is associated with cumulative incidence of LEA in cohorts of people with both type 1 and type 2 diabetes and may help to identify patients at risk for LEA.© 2019 by the American Diabetes Association.

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