Romain Meer ^(1,2), Joyce Y. Xu ^(2,3,4), Simon P. Newsom ⁽¹⁾, Andreas Pasch ^(5,6), Marc G. Vervloet ^(2,7), Pim A. de Jong ⁽⁸⁾, Petra J.M. Elders ^(9,10), Joline W.J. Beulens^(1,2,10,11)

(1) Department of Epidemiology & Data Science, Amsterdam UMC, Amsterdam, The Netherlands (2) Amsterdam Cardiovascular Sciences Research Institute, Amsterdam, The Netherlands (3) Department of Nephrology, Amsterdam UMC, Amsterdam, The Netherlands (4) Department of Laboratory Medicine, Amsterdam UMC, Amsterdam, The Netherlands (5) Calciscon AG, Biel, Switzerland (6) Institute for Physiology and Pathophysiology, Johannes Kepler University Linz, Linz, Austria (7) Department of Nephrology, Radboud University Medical Centre, Nijmegen, The Netherlands (8) Department of Radiology, University Medical Centre Utrecht, Utrecht, The Netherlands (9) Department of General Practice, Amsterdam UMC, Amsterdam, The Netherlands (10) Amsterdam Public Health Research Institute, Amsterdam, The Netherlands (11) Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, The Netherlands

r.meer@amsterdamumc.nl

Background: This study aimed to evaluate the effect of six-month magnesium citrate supplementation on calciprotein crystallization (T₅₀) and carotid-femoral pulse wave velocity (cfPWV) in individuals with type 2 diabetes mellitus (T2DM) and peripheral medial arterial calcification (MAC).

Methods: This double-blind, placebo-controlled trial randomized 74 T2DM participants (78% men, 72 [68-76] years) with peripheral MAC and cfPWV≥12.0 m/s to magnesium citrate (350mg/day; n=37) or placebo (n=37). Nephelometry-based T₅₀ measurements, cfPWV measurements, and 24-hours urine were obtained at baseline, three and six months. Longitudinal analysis of covariance adjusted for baseline T₅₀ and cfPWV was used to study the treatment effects on T₅₀ and cfPWV.

Results: Baseline mean T₅₀ and cfPWV were similar between the magnesium group (T₅₀ 348±54 minutes; cfPWV 15.9±2.2 m/s) and placebo group (362±54 minutes; 15.6±2.0 m/s). Magnesium in serum and in 24-hours urine were lower in the magnesium group (0.74 [0.71-0.77] mmol/L and 3.30 [2.06-4.71] mmol/24h) compared to the placebo group (0.81 [0.74-0.86] mmol/L and 4.31 [3.09-5.54] mmol/24h). Supplementation increased 24-hour urine magnesium excretion (p<0.001), but not serum magnesium concentration (p=0.073) over time in the magnesium group relatively to the placebo group. Magnesium supplementation did not increase T₅₀ (ẞ=6 minutes [-11;22], p=0.491) but did increase cfPWV (ẞ=0.8 m/s [0.1;1.5], p=0.021) over six months in the magnesium group relatively to the placebo group, but the statistical significance was lost after adjusting for clinically relevant baseline differences (T₅₀: ẞ=7 minutes [-12;25], p=0.482; cfPWV: ẞ=0.5 m/s [-0.2;1.3], p=0.180).

Discussion/Conclusion: Six-month magnesium citrate supplementation did not improve T₅₀ and arterial stiffness in T2DM individuals with peripheral MAC.