General Discussion 159 7 as on the ratios reflecting enzymatic activity of 11β-hydroxysteroid dehydrogenases (11β-HSDs) and A-ring reductases. Overall, this thesis aimed to compare several analytic methods for the assessment of magnesium status and to investigate health aspects of magnesium status and magnesium supplementation, focusing on type 2 diabetes (T2D), glucocorticoid metabolism, blood pressure, and arterial stiffness. Health aspects of magnesium status Plasma ionized magnesium In clinical practice, plasma magnesium is most commonly measured as total magnesium with predominant techniques being 1) photometry, which uses a number of chromogenic substances such as xylidyl blue, and 2) atomic absorption spectroscopy 11. Normal total plasma magnesium concentrations range from 0.70-1.00 mmol/L. Magnesium in plasma is bound (mostly) to proteins (20-30%) or present as the ionized form (70-80%). The latter form is considered as the free and biologically active form. Several researchers have therefore suggested that ionized plasma magnesium is a more physiologically relevant marker than total plasma magnesium 11,12. In Chapter 2, we developed and validated an assay for quantifying ionized magnesium in plasma using NMR spectra collected for routine lipoprotein quantification on a clinical laboratory instrument. We observed a strong correlation between NMR-measured ionized plasma magnesium and total plasma magnesium obtained by a photometric method (Roche Modular), indicating that accurate ionized magnesium concentrations can be obtained from NMR spectra. The observed systematic bias confirmed our hypothesis that the two assays quantify systematically different amounts of magnesium; NMR quantifies the free ionized fraction, which is indeed lower than the total fraction that is quantified by the routine clinical assay. Plasma ionized magnesium and TD2 T2D is currently one of the most important public health concerns worldwide and is a major risk factor for cardiovascular diseases 13. Patients with T2D frequently have hypomagnesaemia: its prevalence among patients with T2D ranges from 14% to 48% 14, while the prevalence of hypomagnesaemia among the healthy population is significantly lower (2.5% to 15%). Although the exact mechanism by which T2D affects magnesium levels is unknown, it has been suggested that insulin sensitivity is involved 15. Magnesium stimulates the activity of tyrosine-kinase at the insulin receptor level,
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