Magnesium in Diabetes Mellitus and Diabetic Kidney Disease

Magnesium is a cofactor in cellular energy metabolism and insulin signaling, with recognized effects on vascular tone and cardiac electrophysiology. Hypomagnesemia affects roughly one-third of people with type 2 diabetes mellitus (T2DM) in pooled observational data and becomes more frequent in diabetic kidney disease (DKD). Reduced dietary intake accounts for part of the deficit; renal magnesium wasting linked to attenuated insulin signaling and reduced TRPM6 activity at the distal convoluted tubule is a plausible mechanism for the remainder, characterized mainly in cellular and experimental systems. In observational cohorts, lower serum magnesium accompanies poorer glycemic control and an excess of cardiovascular and microvascular events, and in DKD it independently predicts progression to kidney failure. Prescribed oral repletion has been associated with fewer cardiovascular events in hypomagnesemic patients, with no corresponding association in normomagnesemic ones, in propensity-matched data that cannot substitute for randomized confirmation. Mendelian randomization offers suggestive evidence for coronary artery disease and none for incident T2DM, a dissociation compatible with insulin resistance acting upstream of renal magnesium wasting, although instrument limitations leave other readings open. Hypomagnesemia is substantially less frequent in adult type 1 diabetes, where the association with glycemic control concentrates among patients with the highest insulin requirements. SGLT2 inhibitors raise serum magnesium modestly, whereas thiazide and loop diuretics and proton-pump inhibitors lower it. Randomized trials have shown modest effects on glycemic intermediates, larger in patients with documented deficiency, and no trial has yet tested renal progression. Magnesium status is a reproducible prognostic marker in T2DM and DKD; its value as a therapeutic target awaits randomized trials with clinical endpoints.