The Emerging Role of Magnesium Supplementation for Diabetes
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.
Magnesium Needs in the North American Population
Even by the too low recommended daily allowances, which have been promulgated by the National Academy of Sciences and the Institute of Medicine after great deliberation, research, and literature review, an estimated 85% to 95% of the population of the United States is receiving an inadequate magnesium intake.
Levels of magnesium may be particularly low in certain populations, such as African Americans. For example, the prevalence of hypomagnesemia is 20% among urban African Americans in the city of Buffalo, NY, and surrounding area. This exceeds the prevalence of hypomagnesemia in the general population, and implies a risk for diabetes, hyperlipidemia, hypertension, other cardiovascular disease, and renal disease. Low dietary magnesium intake is correlated with insulin resistance in non-elderly African Americans without diabetes.
The American Diabetes Association (ADA) recognizes the increased risks associated with magnesium deficiency in patients with certain diseases or conditions. In addition, the ADA recommends that magnesium levels be measured in such patients and repleted if deficient.
Magnesium Levels in Patients with Diabetes
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. 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.
According to research, 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 investigations 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. 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 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.
Reasons for Low Magnesium Status in Diabetes
- Diets tend to be low in magnesium.
- Renal excretion of magnesium is high.
- Insensitivity to insulin affects magnesium transport as well as glucose metabolism.
- Use of loop and thiazide diuretics promotes magnesium wasting.
Clinical Implications of Low Magnesium Levels
- Magnesium deficiency is associated with insulin resistance and increased platelet reactivity.
- Reduced intake and reduced levels of magnesium may also lead to increased atherosclerosis. In addition, lower serum magnesium levels have been associated with increased likelihood or progression of retinopathy in type 1 and type 2 diabetes.
- Epidemiologic data suggest that populations with low magnesium intake are at increased risk for hypertension, stroke, and other manifestations of atherosclerotic disease. In the Atherosclerosis Risk in Communities (ARIC) Study, dietary magnesium intake was inversely correlated with ultrasonographically measured carotid artery wall thickness, which is a surrogate marker for atherosclerosis.
Magnesium Supplementation Does the Following:
- Corrects the deficit in intracellular free magnesium levels
- Decreases platelet reactivity
- Improves insulin sensitivity
- May protect against diabetes and its complications
- May reduce blood pressure