Unveiling Silent Atherosclerosis in Type 1 Diabetes: The Role of Glycoprotein and Lipoprotein Lipidomics, and Cardiac Autonomic Neuropathy

<b>Introduction:</b> This study aimed to evaluate whether glycoprotein and lipoprotein lipidomics profiles could enhance a clinical predictive model for carotid subclinical atherosclerosis in patients with type 1 diabetes (T1D). Additionally, we assessed the influence of cardiac autonomic neuropathy (CAN) on these predictive models. <b>Methods:</b> We conducted a cross-sectional study including 256 patients with T1D. Serum glycoprotein and lipoprotein lipidomics profiles were determined using ¹H-NMR spectroscopy. Subclinical atherosclerosis was defined as carotid intima-media thickness (cIMT) ≥ 1.5 mm. CAN was identified using the Clarke score. Predictive models were built and their performance evaluated using receiver operating characteristic curves and cross-validation. <b>Results:</b> Subclinical atherosclerosis was detected in 32% of participants. Patients with both CAN and atherosclerosis were older, had a longer duration of diabetes, and were more likely to present with bilateral carotid disease. Clinical predictors such as age, duration of diabetes, and smoking status remained the strongest determinants of subclinical atherosclerosis [AUC = 0.88 (95%CI: 0.84-0.93)]. While glycoprotein and lipoprotein lipidomics profiles were associated with atherosclerosis, their inclusion in the clinical model did not significantly improve its diagnostic performance. Stratification by the presence of CAN revealed no impact on the model's ability to predict subclinical atherosclerosis, underscoring its robustness across different risk subgroups. <b>Conclusions:</b> In a cohort of patients with T1D, subclinical atherosclerosis was strongly associated with traditional clinical risk factors. Advanced glycoprotein and lipoprotein lipidomics profiling, although associated with atherosclerosis, did not enhance the diagnostic accuracy of predictive models beyond clinical variables. The predictive model remained effective even in the presence of CAN, highlighting its reliability as a screening tool for identifying patients at risk of subclinical atherosclerosis.