Chapter 2 40 Another possible explanation by which low Mg levels affect the risk of T2D might be through chronic inflammation. Markers for systemic inflammation, including CRP and GlycA, have been found to be independent predictors for the risk of developing T2D 28,46. Song and others found that dietary Mg intake was inversely associated with CRP and E-selectin levels in women and recently, it has been shown that low circulating Mg levels were associated with higher CRP levels 47. Furthermore, a meta-analysis of clinical trials showed that Mg supplementation reduces CRP levels, but this finding was only significant in subjects with higher baseline CRP levels 48. In our study, adjustment for CRP did not influence the association between plasma Mg and T2D risk. Measurements of circulating Mg are currently used by physicians to identify patients with hypomagnesemia and hypermagnesemia. Hypermagnesemia or high magnesium may be an indication of renal impairment or failure or in patients with Addison disease. Marked increases in circulating Mg may also be found in patients taking Mg salts, such as those found in antacids, or in pregnant women with preeclampsia who are taking Mg sulfate as an anticonvulsant. Hypomagnesemia can occur in subjects who are on long-term hyperalimentation, intravenous therapy, alcoholism and other types of malnutrition or malabsorption. Mg deficiency has been shown to be associated with cardiac arrhythmias. This study suggests that low plasma Mg may also be useful for assessing the risk of T2D in women. The present study has strengths as well as limitations. The main strengths include the prospective study design and the large sample size. Second, our findings suggest that NMR-measured ionized Mg showed good agreement with Mg measured on the Roche Modular Analyzer and thereby, introducing a novel method to measure circulating Mg that might have useful clinical applications. Some limitations warrant consideration. First, as with any observational study, no cause-effect relationships can be drawn and residual confounding still may exist. Second, because Mg is predominantly present in green leafy vegetables, nuts, whole grains, and legumes, effects of other dietary components could have been responsible for the association between Mg and T2D. Unfortunately, we were not able to adjust for such potential confounders, because no data on dietary intake were available. Third, we had to report separate HRs for men and women, because we found a significant interaction by sex in the analysis. Therefore, the number of cases could have become insufficient to detect an association in men. Fourth, NMR-measured Mg was only assessed at the second screening and therefore, we could not take into account possible changes in Mg concentrations over time. However, one study reported a strong correlation between two Mg concentrations that were
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