Magnesium Metabolism in Insulin Resistance, Metabolic Syndrome, and Type 2 Diabetes Mellitus

Magnesium plays a key role in regulating insulin action, insulin-mediated glucose uptake, and vascular tone. Intracellular magnesium depletion may result in a defective tyrosine–kinase activity at the insulin receptor level, in a postreceptorial impairment in insulin action, and clinically in a worsening of insulin resistance. Intraand extracellular alterations of magnesium metabolism have been identifi ed in clinical states characterized by insulin resistance, such as metabolic syndrome, hypertension, altered glucose tolerance, type 2 diabetes, and aging. Several studies, from our and other’s groups, have confi rmed the clinical relevance of alterations of magnesium homeostasis in these conditions and have highlighted the importance of an accurate defi nition of the magnesium status. While measurements of total serum magnesium levels have been proven inadequate for this purpose because important magnesium depletions are required before total serum level decreases, two technologies, P nuclear magnetic resonance (P-NMR) spectroscopy and magnesium-specifi c ion-selective electrodes, that, respectively, measure intracellular and extracellular free levels of magnesium, have a higher sensitivity in detecting magnesium defi cits. A number of evidences have confi rmed that magnesium supplementation is indicated in conditions associated with magnesium defi cit, although well-designed therapeutic trials with oral magnesium supplements to study the benefi cial effects in metabolic syndrome and in type 2 diabetes are needed. An increasing number of evidences have suggested a clinical relevance for the altered magnesium (Mg) metabolism present in states of increased peripheral insulin resistance. As discussed below, we have suggested a role for Mg defi cit as a possible unifying mechanism of the insulin resistance of hypertension and conditions associated with altered glucose tolerance, including metabolic syndrome and type 2 diabetes mellitus. Our group has used a ion-based approach to demonstrate: (1) the critical importance of Mg metabolism in regulating insulin sensitivity, as well as vascular tone and blood pressure homeostasis; (2) that Mg defi ciency, defi ned on the basis of intracellular free magnesium levels (Mgi), and or serum ionized magnesium (MgI) is a common feature of insulin resistant-states, as well as various cardiovascular and meta-