General Introduction 15 1 much is known about potential health aspects of low plasma ionized magnesium levels. Therefore, in Chapter 2, we study the performance of a nuclear magnetic resonance (NMR)-based assay, that quantifies ionized magnesium in EDTA plasma samples and we prospectively examine the association of plasma magnesium with risk of developing T2D in the Prevention of Renal and Vascular End-stage Disease (PREVEND) study using data from 5747 subjects. Also, there is increasing interest in the measurement of intracellular magnesium concentrations, as a significant amount of the total body magnesium is located in cells. Particularly, the measurement of magnesium in white and red blood cells has become more popular, because these cells are relatively easy to obtain 64. The relevance of intra-erythrocyte measurement has been further emphasized by a previous study showing that the prevalence of hypomagnesemia based on the intra-erythrocyte level was high among geriatric patients, whereas these patients had normal total plasma magnesium concentrations 65. Unfortunately, no simple and rapid technique exists to measure intracellular magnesium concentrations. A laborious direct method has been established to measure magnesium concentrations in erythrocytes. A less laboriously indirect method can calculate intra-erythrocyte magnesium from whole blood magnesium and plasma magnesium by taking into account the hematocrit and is therefore much easier to apply. Whether this method is representative of the intra-erythrocyte magnesium concentration is not well known. Deuster et al. were the first to report a method comparison between a direct and an indirect method for the assessment of intra-erythrocyte magnesium 66, however, using only 10 samples. A larger sample is therefore required in order to perform a valid method comparison. In Chapter 3, we compare a direct and an indirect method for the assessment of intra-erythrocyte magnesium and additionally explore determinants of intra-erythrocyte magnesium using data from the LifeLines cohort study. As magnesium is mainly located in cells, and due to its proposed role in T2D, it was hypothesized that intra-erythrocyte magnesium correlates with T2D markers, such as fasting glucose and HbA1c. Several clinical trials already reported small, yet inconclusive effects on blood pressure following magnesium supplementation. The exact mechanism by which magnesium potentially lowers blood pressure is unknown. In Chapter 4, we review available data on potential mechanisms linking magnesium with blood pressure. Here, we use a physiology-based approach, structuring our analyses based on blood pressure and its immediate determinants, i.e. cardiac output and peripheral resistance.
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