Chapter 2 24 Abstract Background Low circulating magnesium (Mg) is associated with increased risk of developing type 2 diabetes mellitus (T2D). We aimed to study the performance of a nuclear magnetic resonance (NMR)-based assay that quantifies ionized Mg in EDTA plasma samples and prospectively investigate the association of Mg with risk of T2D. Methods The analytic performance of an NMR-based assay for measuring plasma Mg was evaluated. We studied 5747 subjects free of T2D at baseline in the Prevention of Renal and Vascular End-stage Disease (PREVEND) study. Results Passing-Bablok regression analysis, comparing NMR-measured ionized Mg with total Mg measured by the Roche colorimetric assay, produced a correlation of r=0.90, with a slope of 1.08 (95% CI: 1.00-1.13) and an intercept of 0.02 (95% CI: -0.02-0.08). During median follow-up period of 11.2 (IQR: 7.7-12.0) years, 289 (5.0%) participants developed T2D. The association of NMR-measured ionized Mg with T2D risk was modified by sex (Pinteraction=0.007). In women, we found an inverse association between Mg and risk of developing T2D, independent of adjustment for potential confounders (HR: 1.80; 95% CI:1.20-2.70). In men, we found no association between Mg and risk of developing T2D (HR: 0.90; 95%: 0.67-1.21). Conclusion Lower NMR-measured plasma ionized Mg was independently associated with a higher risk of developing T2D in women, but not in men.
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