Severely increased albuminuria in patients with type 2 diabetes mellitus is associated with increased subclinical atherosclerosis in femoral arteries with Na [¹⁸F]F activity as a proxy - The DETERMINE study

Background and aims: Sodium [¹⁸F]fluoride (Na [¹⁸F]F) positron emission tomography imaging allows detailed visualization of early arterial micro-calcifications. This study aims to investigate atherosclerosis manifested by micro-calcification, macro-calcification, and aortic stiffness in patients with type 2 diabetes mellitus (T2DM) with and without albuminuria and severely decreased kidney function. Methods: A cohort was stratified in four groups (N = 10 per group), based on KDIGO categories (G1-5 A1-3). G1-2A1 non-diabetic controls (median [IQR] estimated glomerular filtration rate (eGFR) in mL/min/1.73 m² 91 [81–104]), G1-2A1 with T2DM (eGFR 87 [84–93], and albumin-creatinin-ratio (ACR) in mg/mmol 0.35 [0.25–0.75]), G1-2A3 with T2DM (eGFR 85 [60–103], and ACR 74 [62–122], and G4A3 with T2DM (eGFR 19 [13-27] and ACR 131 [59–304]). Results: Na [¹⁸F]F femoral artery grading score differed significantly in the groups with the highest Na [¹⁸F]F activity in A3 groups with T2DM (G1-2A3 with T2DM 228 [100–446] and G4A3 with T2DM 198 [113–578]) from the lowest groups of the G1-2A1 with T2DM (33 [0–93]) and in G1-2A1 non-diabetic controls (75 [0–200], p = 0.001). Aortic Na [¹⁸F]F activity and femoral artery computed tomography (CT)-assessed macro-calcification was increased in G4A3 with T2DM compared with G1-2A1 with T2DM (47.5 [33.8–73.8] vs. 17.5 [8.8–27.5] (p = 0.006) and 291 [170–511] vs. 12.2 [1.41–44.3] mg (p = 0.032), respectively). Carotid-femoral pulse wave velocity (PWV)-assessed aortic stiffness was significantly higher in both A3 groups with T2DM compared with G1-2A1 with T2DM (11.15 and 12.35 vs. 8.86 m/s, respectively (p = 0.009)). Conclusions: This study indicates that the presence of severely increased albuminuria in patients with T2DM is cross-sectionally associated with subclinical arterial disease in terms of micro-calcification and aortic stiffness. Additional decrease in kidney function was associated with advanced macro-calcifications.