Comparative Subclinical Vascular Damage in Rheumatoid Arthritis and Type 2 Diabetes Mellitus: An Exploratory Propensity-Matched Cross-sectional Study with Vascular Phenotyping and Metabolomics

Purpose Chronic inflammation in rheumatoid arthritis (RA) and metabolic dysregulation in type 2 diabetes mellitus (T2DM) confer increased atherosclerotic cardiovascular disease (ASCVD) risk. However, it remains unclear whether the vascular dysfunction arises from shared or distinct mechanisms. We compared vascular dysfunction and metabolomics between RA and T2DM, and examined disease-specific links between metabolites and vascular measures. Methods In this cross-sectional, propensity-matched study (1:1 by age, sex, body mass index, hypertension, hyperlipidemia) of 58 participants without ASCVD, vascular measurements including brachial artery flow-mediated dilation (FMD), carotid–femoral pulse wave velocity (cf-PWV) and ultrasonography of carotid and femoral arteries were compared between RA and T2DM. Untargeted metabolomics and lipoprotein profiling with multiple-testing control were performed and correlated with vascular measurements. Results Compared with RA, T2DM had higher arterial stiffness (cf-PWV, 12.8 vs 10.9 m/s; P = 0.005), endothelial dysfunction (FMD < 7%: 79.3% vs 69.0%; P = 0.021), and higher plaque burden (24.1% vs 3.4%; P < 0.001). Metabolomics profiling showed several differences in amino acids and ketone intermediates between RA and T2DM. Lipoprotein–vascular links were disease-specific with low-density lipoprotein (LDL) subclasses dominating the vascular associations in RA, and small dense high-density lipoprotein (HDL) in T2DM. In RA, 2-ketoisovalerate was inversely related to FMD (r = − 0.49; P = 0.007), while alanine, glucose, glutamate, and 4-hydroxyphenylacetate were associated with higher cf-PWV or CIMT; in T2DM, alanine inversely correlated with CIMT (r = − 0.39; P = 0.035). Conclusions In this contemporary cohort, T2DM showed greater vascular dysfunction than RA. Distinct metabolic profiles, with disease-specific vascular correlates, support tailored risk stratification and targeted cardiovascular prevention in RA versus T2DM.