The link between diabetes mellitus and magnesium deficiency is well known. A growing body of evidence suggests that magnesium plays a pivotal role in reducing cardiovascular risks and may be involved in the pathogenesis of diabetes itself. While the benefits of oral magnesium supplementation on glycemic control have yet to be demonstrated in patients, magnesium supplementation has been shown to improve insulin sensitivity. Based on current knowledge, clinicians have good reason to believe that magnesium repletion may play a role in delaying type 2 diabetes onset and potentially in warding off its devastating complications -- cardiovascular disease, retinopathy, and nephropathy.
Many studies have shown that both mean plasma and intracellular free magnesium levels are lower in patients with diabetes than in the general population. This magnesium deficiency, which may take the form of a chronic latent magnesium deficit rather than clinical hypomagnesemia, may have clinical importance because the magnesium ion is a crucial cofactor for many enzymatic reactions involved in metabolic processes.
Many studies show that mean plasma levels are lower in patients with both type 1 and type 2 diabetes compared with non-diabetic control subjects. The concentration of intracellular free magnesium in erythrocytes is a more sensitive marker in people with diabetes and insulin resistance than are plasma levels of magnesium. Decreased levels of free intracellular magnesium in erythrocytes have been reported in the majority of patients with type 2 diabetes.
Resnick and associates suggest that extracellular and intracellular magnesium deficiency is typical in chronic, stable, mild type 2 diabetes and may be a strong predisposing factor for the development of the excess cardiovascular morbidity associated with diabetes. These investigators showed that the levels of serum ionized magnesium and erythrocyte intracellular free magnesium were significantly lower in 22 untreated patients with type 2 diabetes and mild hyperglycemia than they were in 30 healthy control subjects (P< .001). Serum total magnesium was not reduced.
Magnesium loss and insulin resistance
Among its many actions, insulin stimulates the transport of magnesium from the extra-cellular to the intracellular compartment. Using atomic absorption spectrophotometry and the euglycemic hyperinsulinemic glucose clamp technique, Paolisso and associates showed that plasma magnesium level declined and erythrocyte magnesium levels rose significantly (P< .05) in response to insulin in fasting healthy adults with no family history of diabetes.
Insulin resistance -- central to type 2 diabetes -- is associated with reduced intracellular magnesium and can be mitigated with magnesium. It has been demonstrated that insulin resistance in skeletal muscle can be reduced by magnesium administration.
Reduced magnesium levels in diabetes are caused by several factors. The link between magnesium deficiency and the development of diabetes is strengthened by the observation that several treatments for type 2 diabetes appear to increase magnesium levels.
Metformin, for example, raises magnesium levels in the liver. Pioglitazone, a thiazolidinedione antidiabetic agent that increases insulin sensitivity, increases free magnesium concentration in adipocytes.
Jerry L. Nadler, MD;