Asymmetric Dimethylarginine as a Potential Biomarker for Cardiovascular Risk Assessment in Long-Standing Type 1 Diabetes Mellitus

Introduction. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, is a marker of endothelial dysfunction and has been linked to vascular injury. Its clinical relevance for cardiovascular risk (CVR) assessment in adults with long-standing type 1 diabetes mellitus (T1DM) remains unclear. The objective of this study was to examine whether serum ADMA levels relate to established CVR stratification models and to explore their associations with key clinical variables relevant to vascular risk (albuminuria (AlbU), glycated hemoglobin (HbA1c), diabetes duration, and sex). Methods. This cross-sectional study included 124 adults with long-standing T1DM and 59 age- and sex-matched non-diabetic controls. Serum ADMA was measured by ELISA; C-reactive protein (CRP), HbA1c, and AlbU were quantified using standardized clinical laboratory methods. CVR was assessed using the Steno Type 1 Risk Engine (ST1RE), the 2019 European Society of Cardiology Guidelines on Diabetes, Pre-Diabetes and Cardiovascular Diseases (ESC 2019), and a composite RiskFactor3 model integrating CRP, HbA1c, and AlbU categories. Non-parametric methods were applied due to non-normal distributions. Results. ADMA levels did not differ significantly between the T1DM and control group (0.49 [0.32–0.68] vs. 0.56 [0.43–0.69] μmol/L, p = 0.092). Within the T1DM cohort, ADMA correlated positively with AlbU (p = 0.004) but showed no meaningful associations with age, diabetes duration, HbA1c, or CRP. A multivariable regression, including AlbU and HbA1c, explained 15% of ADMA variability (p < 0.001). ADMA values overlapped extensively across the ST1RE, ESC 2019, and RiskFactor3 categories. Receiver operating characteristic analyses demonstrated limited overall discriminatory capacity (AUC ≈ 0.5). In females, a trend toward moderate discrimination was observed for identifying ≥ 2 RiskFactor3 components (AUC = 0.653, 95% CI (0.565–0.881), p = 0.067). Conclusions. Serum ADMA is not a universal marker of global CVR in adults with long-standing T1DM. Its strongest clinical association was with AlbU, consistent with renal-endothelial stress rather than overall CVR burden as defined by multivariable risk equations. The observed sex-specific signal in females warrants further investigation. Larger prospective studies are needed to determine whether ADMA may have targeted value in phenotype-specific or sex-specific CVR assessment strategies.