Abstract Aim To identify predictors of incident cardiovascular disease (CVD) in patients with type 2 diabetes mellitus (T2DM) over more than four years of follow-up. Methods A total of 190 patients with T2DM were followed for a mean duration of 4.76 years. Baseline demographic, anthropometric, laboratory, and CVD-related biomarker profiles were obtained at baseline and follow-up. At baseline, 105 patients (55.3%) had established CVD. The remaining 85 patients without CVD were classified as CVD progressors (developed CVD at follow-up, n=31) or non-progressors (no CVD at follow-up, n=54). Between-group comparisons, delta-change analysis, and multivariable logistic regression (adjusted for demographics, diabetes duration, medications, comorbidities, and smoking) were performed to determine independent predictors of CVD development. Results At baseline, the cohort had a mean age of 50.23 ? 7.3 years, 51.6% were males, and the mean diabetes duration was 12.02 ? 5.9 years. Over follow-up, significant increases were noted in systolic blood pressure, AST, total bilirubin, alkaline phosphatase, HDL, and multiple CVD biomarkers (A2M, fetuin, L-selectin, SAP, adipsin) (all p< 0.05), while BMI, waist/hip circumference, GGT, albumin, and HbA1c significantly decreased (p < 0.01). Among the 85 patients without baseline CVD, 31 (36.5%) developed CVD. Progressors had a greater decline in platelet count (-19.42 vs +8.92, p=0.011) and a greater increase in PF4 (+0.80 vs +0.01, p=0.009). Platelet decline correlated negatively with CVD risk (r=-0.296, p=0.006), whereas PF4 elevation correlated positively (r=0.284, p=0.009). Multivariable regression consistently identified decreasing platelet count (OR 0.981-0.985, p=0.015) and increasing PF4 levels (OR 1.557-1.760, p=0.026) as independent predictors of incident CVD. SGLT2 inhibitor use was associated with a significantly lower risk of CVD (adjusted OR 0.311, 95% CI 0.119-0.817, p=0.018), while GLP-1 receptor agonists and DPP-4 inhibitors use showed non-significant trends towards risk reduction. Conclusion In patients with T2DM, a decrease in platelet count and an increase in PF4 independently predict incident CVD, highlighting the contribution of platelet activation to cardiovascular risk. In addition, SGLT2 inhibitor therapy appears to confer a significant protective effect against CVD in this high-risk population. Funding This project was funded by the National Plan for Science, Technology and Innovation (MAARIFAH), King Abdulaziz City for Science and Technology, Saudi Arabia (Project No. 08-MED513-02).
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