Background: Individuals with diabetes are at higher risk for developing arterial disorders. The toe-brachial index (TBI) is associated with peripheral vascular disease, and aortic pulse-wave velocity (aPWV) is currently the gold standard for assessing arterial stiffness. High concentrations of plasma arginine vasopressin (AVP) preferentially stimulate V1a receptors, which affect the vascular bed and may contribute to cardiovascular (CV) complications. Copeptin, a more stable peptide of AVP, is co-secreted from the pituitary gland in equimolar amounts to AVP upon hemodynamic, osmotic, and other stress-related stimuli. Elevated levels of copeptin are potentially linked to vascular dysfunction.

Objective: To analyze the association of copeptin to TBI and aPWV as a marker of arterial disorder in patients with type 2 diabetes mellitus (T2D).

Methods: A cross-sectional analysis was conducted on 681 patients from the epidemiological study CARDIPP (Cardiovascular Risk Factors in Patients with Diabetes – a Prospective Study in Primary Care; ClinicalTrials.gov identifier NCT01049737) with data on copeptin, TBI, and aPWV. The relationship between the conventional cardiovascular risk factors and copeptin with TBI and aPWV were examined, respectively. Pearson correlation analysis and linear regression analyses were used.

Results: Copeptin correlated to TBI (r=-0.086, P=0.027) and aPWV (r=0.143, P<0,001). Copeptin was also negatively associated with TBI (β=-0.093, P=0.027) and aPWV (β=0.121, P=0.004) independently of age, sex, diabetes duration, BMI, smoking, previous cardiovascular diseases, HbA1c, HDL cholesterol, and estimated glomerular filtration rate.

Conclusion: Copeptin is independently associated with TBI and aPWV. Copeptin may play an important role in the development of arterial disorders. Measuring copeptin levels may be a simpler method and more efficient way to identify individuals at risk for arterial disorders compared to current methods such as TBI and aPWV.