For patients with type 1 or 2 diabetes, plasma copeptin level may be associated with cumulative incidence of lower-extremity amputations, according to study results published in Diabetes Care.

Researchers assessed whether plasma copeptin, a surrogate marker of vasopressin, is associated with lower-extremity amputation in diabetes, a significant and burdensome complication of diabetes for which predictive biomarkers are lacking.

The study included patients from 4 cohorts who had type 1 or type 2 diabetes. The researchers used an immunoluminometric assay to measure copeptin concentration in baseline plasma samples. During a median follow-up of 5 to 10 years, they assessed the association between baseline plasma copeptin and risk for lower-extremity amputation. Plasma copeptin levels were log transformed to adjust for positive skewness.

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In participants with type 1 diabetes (n=710), the cumulative incidence of lower-extremity amputation during follow-up by increasing tertiles of baseline plasma copeptin was 3.9% for tertile 1, 3.3% for tertile 2, and 10.0% for tertile 3 (P =.002).

After performing Cox regression analyses, the researchers found that copeptin was associated with lower-extremity amputation in patients with type 1 diabetes, with a hazard ratio of 1.89 (95% CI, 1.28-2.82) for 1 SD of log[copeptin] (P =.002).

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In patients with type 2 diabetes (n=4553), the cumulative incidence of lower-extremity amputation was 1.1% for tertile 1, 2.9% for tertile 2, and 3.6% for tertile 3 (P <.0001).

Cox regression analyses indicated that baseline plasma copeptin was significantly associated with lower-extremity amputation in patients with type 2 diabetes. The hazard ratio for 1 SD increment of log[copeptin] was 1.42 (95% CI, 1.15-1.74; P =.001).

The study had several limitations, including its observational design and use of copeptin as a surrogate for vasopressin.

“Plasma copeptin could possibly help to identify patients with diabetes and high risk of [lower extremity amputation], due to the relationship between copeptin and hydration status. Our results raise the hypothesis that optimization of hydration through lifestyle recommendations (increased water drinking) could alleviate this risk,” the researchers wrote.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

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Potier L, Roussel R, Marre M, et al. Plasma copeptin and risk of lower-extremity amputation in type 1 and type 2 diabetes [published online October 3, 2019]. Diabetes Care. doi:10.2337/dc19-1062