Lower plasma magnesium, measured by nuclear magnetic resonance spectroscopy, is associated with increased risk of developing type 2 diabetes mellitus in women: Results from a Dutch prospective cohort study 39 2 Our prospective findings showed that NMR-measured ionized Mg was associated with increased risk of T2D in women even after adjusting for traditional T2D risk factors and CRP. However, we found no association between NMR-measured Mg and risk of developing T2D in men. No other studies have reported such an interaction with sex in the association of circulating Mg and risk of T2D. This is therefore the first study demonstrating an inverse association of Mg on T2D risk that is only present in women. The interaction between circulating Mg levels and sex may warrant confirmation in further studies. It might be that female sex hormones play a role in this observed interaction 32. It has indeed been established that estrogen significantly affects renal magnesium handling 33,34, likely explaining higher circulating Mg levels in premenopausal women than in post-menopausal women and cycling of Mg levels in premenopausal women 35,36. Low circulating Mg levels and T2D are known to be related, mainly through insulin resistance rather than through insulin secretion, but cause and effect relationships remain to be established 10. Consistent with this, it has been observed that low circulating Mg levels are associated with diabetes, insulin resistance and obesity in women, but not in men 37. It has also been shown that there is a sex difference in the relationship of urinary magnesium excretion to glycaemic control in patients with T1DM 38. Albeit not in the field of diabetes, it has repeatedly been suggested that there is a sex-difference in the prospective association of Mg intake and low circulating Mg levels with cardiovascular mortality, with associations predominantly present in or limited to women 39–41. So far, only three studies prospectively reported associations between serum or plasma Mg and risk of developing T2D 42–44. Everett et al. investigated the relationship between circulating Mg and risk of developing T2D in a cohort of 9784 US participants 43. They showed that low serum Mg was associated with an increased risk of T2D in the total population. Recently, Kieboom et al. confirmed this finding and showed that the association was partly mediated through insulin resistance 44. In the present study, the association between NMR-measured Mg and T2D remained significant after adjusting for fasting glucose levels, which is also in line with the findings from Kao et al. 42. Indeed, the effect of Mg on insulin actions could be one possible mechanism by which Mg affects T2D risk. Mg is essential for autophosphorylation of the β-subunits of the insulin receptor; in vitro studies have shown that Mg enhances tyrosine kinase activity by increasing the receptor’s affinity for ATP.Thus, intracellular Mg deficiencymay result in decreased tyrosine kinase activity and consequently in insulin resistance. Furthermore, clinical trials have shown that Mg supplementation is effective in reducing fasting plasma glucose in diabetic patients and HOMA-IR in individuals at risk of T2D 45.
RkJQdWJsaXNoZXIy MTk4NDMw