Elevated Copeptin is Associated with Atherosclerosis and Diabetic Kidney Disease in Adults with Type 1 Diabetes

Background: Vasopressin exerts important cardio-renal effects, but remains problematic to measure. Copeptin is a more stable peptide derived from the same precursor molecule. We examined the associations between copeptin, coronary artery calcium (CAC), albuminuria and impaired glomerular filtration rate (GFR) in adults with type 1 diabetes (T1D).

Methods: Participants with (n=209) and without T1D (n=244) in the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study were assessed for serum copeptin, CAC measured using 128-slice spiral CT, urinary albumin-to-creatinine ratio (UACR) and eGFR calculated by CKD-EPI creatinine. Impaired GFR was defined as eGFR <60mL/min/1.73m(2), albuminuria as UACR ≥30mg/g, high and very high CAC score as ≥100 and ≥300AU, and elevated copeptin as >13pmol/L (>97.5th percentile for healthy adults). Unadjusted and adjusted (age, sex, HbA1c, SBP and LDL-C) logistic models were applied to examine the relationships.

Results: Participants with T1D had greater ultrasensitive copeptin concentrations than non-diabetics (3.5 [95% CI 2.3-3.8] vs. 2.8 [2.7-3.1], p=0.003). In participants with T1D, elevated copeptin was associated with greater odds of impaired eGFR (OR: 18.52, 95% CI 4.03-85.02), albuminuria (10.55, 2.24-49.62), high CAC (6.61, 1.39-31.31) and very high CAC (6.24, 1.51-25.90) in multivariable models. Similar linear relationships were obtained with ultrasensitive copeptin, eGFR, UACR, CAC volume and CAC score in adjusted models.

Conclusion: In this cross-sectional analysis, copeptin was strongly associated with diabetic kidney disease and coronary atherosclerosis in adults with T1D. Further research is needed to determine whether these relationships hold true longitudinally in people with T1D.