Abstract Aim To evaluate early, before the onset of cardiovascular events and of chronic renal insufficiency, the association between chronic kidney disease (CKD)-mineral bone disorder (MBD) biomarkers and vascular stiffness [Cardio Ankle Vascular Index (CAVI)] in the course of type 2 diabetes (T2DM). Method We evaluated 174 T2DM patients [median age 56 years; male/female (M/F) 100/74] with diabetes duration < 10 years and without decreased estimated glomerular filtration rate (eGFR; ≥60 mL/min/1.73 m2) or macrovascular complications. Thirty-four age-matched healthy subjects [M/F 13/21; age 53.5 (50.0-57.7) years; eGFR 107.5 (97.0-119.7) mL/ min1.73 m2] served as local reference control for CAVI (pathological: ≥8) and the novel CKD-MBD biomarkers. Results Albumin-to-creatinine ratio (ACR) averaged 8.5 mg/g (5.6-17.2) with 12.6% of the patients showing pathologic values, indicative of incipient diabetic nephropathy. Serum parathyroid hormone, fibroblast growth factor 23, and sclerostin were higher while 1,25-dihydroxyvitamin D and Klotho were lower than a control group. CAVI was normal (<8) in only 54% and correlated positively with age (P < 0.001), hemoglobin 1A1c (P = 0.036), and systolic (P = 0.021) and diastolic blood pressure (DBP) (P = 0.001) and negatively correlated with 25-hydroxyvitamin D (P = 0.046). In multivariate analysis, age, DBP, ACR, and serum Klotho were independent positive predictors of CAVI. Conclusion In the absence of overt cardiovascular disease and of chronic renal insufficiency, CAVI is frequently pathologic in T2DM. DBP and ACR are modifiable risk factors of vascular stiffness in T2DM, thus warranting optimal assessment.