Objective: Diabetes mellitus (DM) leads to accelerated progression of arteriosclerosis with an increased risk of coronary events in comparison to non-diabetic patients with coronary artery disease (CAD). The precise and early detection of DM-induced vascular alterations is crucial to identify patients with high risk for cardiovascular complications. Thus, we aimed at simultaneously characterizing functional, physicomechanical, and structural vascular alterations in diabetic patients using a non-invasive approach. Research Design and Methods: In CAD patients with and without type 2 diabetes mellitus (n=50), we non-invasively measured flow-mediated dilation (FMD) of the brachial artery as a marker for endothelial function, fractional diameter changes (FDC) as a marker for physicomechanical properties, intima-media thickness (IMT) as a marker for structural properties, and forearm blood flow (FBF) as a marker for microvascular function. Results: DM was associated with reduced FMD (2.5 +/- 0.2 vs 4.8 +/- 0.4%; p <= 0.001) indicating impaired macrovascular endothelial function. In parallel, reduced FDC (0.024 +/- 0.002 vs 0.034 +/- 0.004; p <= 0.05) and increased IMT (0.38 +/- 0.01 vs 0.31 +/- 0.01mm; p <= 0.001) indicated increased stiffness and enhanced structural alterations. Furthermore, reduced forearm blood flow during reactive hyperemia (10.7 +/- 1.0 vs. 15.3 +/- 1.4mL/ min*100mL; p <= 0.05) was found indicating microvascular dysfunction. Plasma glucose and HbA(1c) correlated with FMD (glucose: r=-0.32; HbA(1c):r=-0.45), IMT (glucose: r=0.54; HbA(1c): r=0.48) and FBF (glucose: r=-0.30) suggesting diabetes-specific effects on vascular properties. Conclusion: In patients with CAD, DM leads to functional and structural vascular alterations of the peripheral vasculature which are determined by the control of the disease underlining the relevance of a strict control of the DM to prevent accelerated atherosclerosis.