Abstract Background While [¹⁸F]-fluordeoxyglucose ([¹⁸F]FDG) uptake is associated with arterial inflammation, [¹⁸F]-sodium fluoride ([¹⁸F]NaF) is a marker for arterial micro-calcification. We aimed to investigate the prospective correlation between both PET markers over time and whether they are prospectively ([¹⁸F]FDG) and retrospectively ([¹⁸F]NaF) related to progression of systemic arterial disease in a longitudinal study in patients with type 2 diabetes mellitus (T2DM). Methods Baseline [¹⁸F]FDG PET/Low Dose (LD) Computed Tomography (CT) scans of ten patients with early T2DM without cardiovascular history (70% men, median age 63 years) were compared with five-year follow-up [¹⁸F]NaF/LDCT scans. Systemic activity was expressed as mean target-to-background ratio (_meanTBR) by dividing the maximal standardized uptake value (SUV_max) of ten arteries by SUV_mean of the caval vein. CT-assessed macro-calcifications were scored visually and expressed as calcified plaque (CP) score. Arterial stiffness was assessed with carotid-femoral pulse wave velocity (PWV). Five-year changes were expressed absolutely with delta (Δ) and relatively with %change. Results Baseline _meanTBR[¹⁸F]FDG was strongly correlated with five-year follow-up _meanTBR[¹⁸F]NaF (r = 0.709, P = .022). _meanTBR[¹⁸F]NaF correlated positively with ΔCPscore, CPscore at baseline, and follow-up (r = 0.845, P = .002 and r = 0.855, P = .002, respectively), but not with %change in CPscore and PWV. Conclusion This proof-of-concept study demonstrated that systemic arterial inflammation is an important pathogenetic factor in systemic arterial micro-calcification development.