Prognostic value of osteoprotegerin for estimation of cardiovascular risk in patients with long-standing type 1 diabetes mellitus

Background: Cardiovascular disease (CVD) is a major complication in patients with long-standing type 1 diabetes (T1D). Osteoprotegerin (OPG) has been proposed as a biomarker for cardiovascular risk (CVR), though its utility in this context requires further evaluation. This study aimed to assess the prognostic signifi cance of OPG in CVR estimation among T1D patients using specifi c CVR assessment tools. Patients and Methods: This prospective case–control study includes 183 participants: 124 with T1D (53.2% men, aged 42.7 ± 10.4 years, diabetes duration 25.3 ± 8.2 years) and 59 healthy controls (54.1% men, aged 45.1 ± 9.1 years). Serum OPG levels were determined via ELISA; CRP – immune-turbidimetric method (Advia chemistry 1800); HbA1C (%) – immuno-inhibition assay (ADVIA chemistry 1800); AlbU (mg/l) – immuno-turbidimetric analysis (Olympus AU600). CVR evaluation tools: STENO Type 1 Risk Engine (ST1RE) and ESC – 2019 guidelines. A RiskFactor3 model combined CRP ≥ 3 mg/l, HbA1C ≥ 7%, and AlbU ≥ 30 mg/l. Results: No signifi cant intergroup differences in OPG levels were observed. However, OPG was observably higher in women  across both groups (T1D: 5.34 ± 1.2 pmol/l vs. 5.73 ± 1.83 pmol/l; controls: 5.06 ± 1.65 pmol/l vs. 6.16 ± 2.38 pmol/l, p < 0.05). In T1D patients, age (R² = 3%), disease duration (R² = 4.8%), and AlbU (R² = 3.9%) were signifi cant positive determinants of OPG (p < 0.05). According to ESC-2019, 30.6% of T1D patients had high CVR and 69.4% had very high CVR. ST1RE classifi ed 38.7% as low, 28.2% as moderate, and 33.1% as high CVR. ST1RE’s AUC-ROC for males was 0.716 (p = 0.005) with a cut-off of 5.075 pmol/l, and for females, 0.683 (p = 0.039) with a cut-off of 5.355 pmol/l. For ESC-2019, the AUC-ROC for females was 0.644 (p = 0.102) with a cut-off of 5.025 pmol/l. Conclusion: OPG is a promising biomarker for assessing CVR in patients with long-standing T1D. Higher OPG levels in women and its associations with age, disease duration, and AlbU emphasize its potential prognostic role. Using ST1RE and ESC-2019, OPG effectively stratifi ed patients by CVR. Incorporating OPG into clinical practice could improve early detection and personalized management of CVR in T1D patients.