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

M Reijrink; J K E Sluiter; C A Te Velde-Keyzer; M H de Borst; G D van Praagh; M J W Greuter; G Luurtsema; H H Boersma; R A Pol; J L Hillebrands; P R van Dijk; K Hoogenberg; D J Mulder; R H J A Slart

doi:10.1016/j.atherosclerosis.2023.117199

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

Atherosclerosis. 2023 Jul 29:117199. doi: 10.1016/j.atherosclerosis.2023.117199. Online ahead of print.

Authors

M Reijrink¹, J K E Sluiter², C A Te Velde-Keyzer³, M H de Borst³, G D van Praagh⁴, M J W Greuter⁵, G Luurtsema⁴, H H Boersma⁶, R A Pol⁷, J L Hillebrands⁸, P R van Dijk⁹, K Hoogenberg¹⁰, D J Mulder², R H J A Slart¹¹

Affiliations

¹ University of Groningen, University Medical Center Groningen, Dept. Internal Medicine, div. Vascular Medicine, the Netherlands. Electronic address: m.reijrink@umcg.nl.
² University of Groningen, University Medical Center Groningen, Dept. Internal Medicine, div. Vascular Medicine, the Netherlands.
³ University of Groningen, University Medical Center Groningen, Dept. Internal Medicine, div. Nephrology, the Netherlands.
⁴ University of Groningen, University Medical Center Groningen, Dept. Nuclear Medicine and Molecular Imaging, the Netherlands.
⁵ University of Groningen, University Medical Center Groningen, Medical Imaging Center, Department of Radiology, Groningen, the Netherlands.
⁶ University of Groningen, University Medical Center Groningen, Dept. Nuclear Medicine and Molecular Imaging, the Netherlands; University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, the Netherlands.
⁷ University of Groningen, University Medical Center Groningen, Department of Vascular and Transplant Surgery, Groningen, the Netherlands.
⁸ University of Groningen, University Medical Center Groningen, Dept. Pathology and Medical Biology, div. Pathology, the Netherlands.
⁹ University of Groningen, University Medical Center Groningen, Dept. Internal Medicine, div. Endocrinology, the Netherlands.
¹⁰ Department of Internal Medicine, Martini Hospital, Groningen, the Netherlands.
¹¹ University of Groningen, University Medical Center Groningen, Dept. Nuclear Medicine and Molecular Imaging, the Netherlands; University of Twente, Dept. of Biomedical Phototonic Imaging, Enschede, the Netherlands.

PMID: 37550141
DOI: 10.1016/j.atherosclerosis.2023.117199

Abstract

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.

Keywords: Albuminuria; Atherosclerosis; Calcification; Computed tomography; Na [(18)F]F positron emission tomography; Type 2 diabetes mellitus.