Why should I proactively recommend magnesium supplementation for my type 2 diabetic patients?

80% of type 2 diabetics may have a low intracellular magnesium levels⁵.

Magnesium deficiency is commonly seen in type 2 diabetes, because high glucose levels cause magnesium to be flushed from the body.

Insulin Levels - In a recent clinical study, four months of magnesium supplementation improved insulin sensitivity⁶. Magnesium works with glucose to improve insulin regulation.

Glucose Control - High blood glucose levels are detrimental to the body. In the same clinical study, four months of magnesium supplementation lowered fasting glucose levels⁶.

Heart Health - Several studies have shown magnesium to lower the risk of developing heart conditions such as coronary artery disease and arrhythmias⁷.

Chances are, many of your type 2 diabetic patients have magnesium deficiency. Even if a patient eats foods high in magnesium (leafy greens for example), he/she still may become deficient because type 2 diabetes causes essential nutrients to be flushed from the body.

Magnesium and The Diabetic

With the prevalence of diabetes increasing and the demands for diabetes care placing increased stress on the health care system, clinical and research attention seeks to more fully understand and manage the underlying metabolic imbalances that lead to poor glucose control and the resultant disease processes that arise from it.

It is now widely accepted that insulin resistance is a core metabolic defect in individuals with type 2 diabetes⁸.

Simply stated, insulin resistance is a failure to effectively utilize insulin to transport glucose into the cells which use that glucose for fuel. This failure occurs at the entry site into the cells which utilize glucose, and is known as the receptor site. It is at this site that insulin signals the cells to allow glucose to pass through. As a result of this failure, glucose levels remain high in the blood. This is known as hyperglycemia, or high blood sugar.

This impaired sensitivity of the cell receptor to insulin, and the resulting high circulating glucose levels are associated with an array of metabolic disorders, referred to as Metabolic Syndrome, which place the diabetic at risk for diseases of the cardiovascular system. These include high blood pressure, high cholesterols and triglycerides, and an increased risk of heart attack and stroke.

Efforts to control insulin resistance include medications which increase the cell's uptake of glucose, and others which stimulate the pancreas to produce more insulin in an attempt to override the resistance at the receptor cell. Along with medications for blood pressure and cholesterol, these medical approaches manage the metabolic disorders that lead to the cardiovascular diseases associated with diabetes. As it is well known that obesity is a predictor for insulin resistance, lifestyle changes, which improve glucose tolerance and reduce heart disease risk with diet and exercise are at the core of any diabetes treatment plan.

As research continues to better understand where the body's glucose management goes awry, leading to insulin resistance, metabolic syndrome and diabetes, mounting evidence has been accumulating for the role the mineral magnesium plays in maintaining glucose balance and cardiovascular health. Studies are now suggesting that magnesium deficiencies are common in diabetics, and may be a preceding factor in insulin resistance and hyperinsulinemia⁹. Studies also suggest the benefit of sufficient dietary magnesium in the prevention^10-11 and reduction of metabolic imbalances associated with diabetes^12-15 and in the risk for resulting cardiovascular diseases^{8, 10-11}.

Magnesium, Diabetes, and Metabolic Syndrome
Magnesium is one of the most abundant minerals in the human body and is utilized in many functions, including the regulation of heart and blood vessel contraction and relaxation, and blood pressure. Magnesium also works with glucose concentrations to regulate insulin sensitivity, and it has been suggested that deficiencies in magnesium seem to be a factor in the derangement of insulin sensitivity and possibly in the development of type 2 diabetes^12-11. Several large population studies have found an inverse relationship between dietary and serum magnesium levels and the incidence of type 2 diabetes^{10-11, 14}.

Data which have investigated the reasons for low cellular magnesium have found that the typical US diet is significantly deficient in magnesium rich foods^{8, 10-11}. Additionally, it has been shown that the urinary excretion of magnesium is elevated in diabetic and prediabetic individuals who are not in good glycemic control⁸, suggesting a cycle which then feeds back to worsening insulin resistance and metabolic derangement. One such study concludes that "it seems reasonable to suggest (a) the critical importance of magnesium metabolism in regulating insulin sensitivity as well as vascular tone, and blood pressure homeostasis; [and] (b) that magnesium deficiency, defined on the basis of intracellular free magnesium levels, is a common feature of both diabetic and hypertensive states⁹."

Magnesium is shown to produce significant effects in the following features of diabetes and metabolic syndrome:

Glucose Control
As previously stated, cellular magnesium seems to play an important role in glucose metabolism, both in regulating glucose's entrance into the cell where it can be utilized for fuel, and in its involvement in key enzymatic reactions in the metabolism of glucose for energy ⁸. Studies indicate that diabetics who supplement with magnesium show significantly lower levels of resting blood glucose than controls, indicating improved metabolism of glucose^{8, 10-11}.

Insulin Resistance
Multiple studies have confirmed that diabetics and non-diabetics with insulin resistance who supplement with magnesium for three months show significant positive changes in their Homeostasis Model Assessment for Insulin Resistance (HOMA-IR)^13-14.

Further, in the Women's Health Study, a large population study in the U.S., insulin levels of overweight women (overweight as indicated by Body Mass Index, a known indicator of insulin resistance and metabolic syndrome) were lowest in the group with the highest dietary intake of magnesium. Lower insulin levels are indicative of good insulin and glycemic control, and these subjects also had the lowest incidence of diabetes in the study¹¹.

Hemoglobin A1c's
As a critical measure of diabetic control, every diabetic should know that their glycosylated hemoglobin test is the best measure of their average glucose tolerance, and of their risk for heart disease complications. Any glucose which is not taken up by the cells and utilized as fuel remains attached to hemoglobin cells, which carry oxygen throughout the bloodstream. The greater the amount of unused, and therefore, excess glucose (hyperglycemia), the greater the percentage of glucose binding to hemoglobin in the bloodstream. This binding of sugar to circulating hemoglobins is a main candidate for the creation of complications from diabetes. As excess glucose stays attached to hemoglobin for the life of the cell, and as the life of hemoglobin cells is approximately 3-4 months, the glycosylated hemoglobin test is an indication of average glucose control over time. Achieving A1c's below 7-8% is possibly the major clinical goal of diabetes treatment.

Several studies show both an inverse relationship between magnesium levels and A1c's in diabetic patients, as well as a significant reduction of A1c's with three months of magnesium supplementation over controls^{8, 12-13}. Although some studies show no effect of magnesium supplementation on A1c's, some of this difference may be explained by study design differences. What does appear consistent at this time in the A1c studies is the inverse relationship between sufficient magnesium status and A1c's, again reinforcing the hypothesis that magnesium is important to good metabolic control in diabetes.

Cardiovascular Complications of Diabetes
A complex of cardiovascular complications is associated with diabetes including hypertension, hyperlipidemia and stroke. Along with insulin resistance and obesity, this complex of diabetes-associated complications is commonly referred to as Metabolic Syndrome or Cardio-Metabolic Syndrome.

One study⁹ discusses the nature of hyperinsulinemia as a prooxidant and proinflammatory state associated with hypertension and cardiovascular disease; that is to say, hyperinsulinemia creates an inflammatory response and resulting vessel damage seen in hypertension and cardiovascular disease. They review data which indicates a role for altered magnesium metabolism in cardiovascular damage induced by this oxidative and inflammatory process, and state that magnesium deficiency is associated with increased oxidative tissue damage. They remark that "the lower the intracellular free magnesium, the stiffer the blood vessels, the higher the blood pressure, and the greater the insulin resistance."

As it relates to hypertension, a strong analysis of studies utilizing magnesium supplementation indicates that there is a dose-dependent improvement in blood pressure with magnesium supplementation¹⁹.

Of great importance to note is the effect on magnesium status of thiazide medications for hypertension^20-21. Thiazide diuretics are often a first-order antihypertensive therapy, and it is well known that hypokalemia and hypomagnesemia are metabolic alterations associated with their long-term use. The occurrence of heart arrhythmias are shown to significantly correlate with decreases in serum potassium and magnesium levels during thiazide therapy. Hollifield confirms that both hypokalemia and hypomagnesemia are independent variables in the onset of ventricular rhythm disturbances, and that abolishment of these thiazide induced abnormalities were effectively accomplished with supplementation of potassium and magnesium. Other studies have confirmed these findings, demonstrating a reduction in the occurrence of rhythm disturbances with potassium and magnesium administration^22-23.

Along with increases in blood pressure, many diabetic patients also grapple with increases in cholesterols and triglycerides, which place them at increased risk for heart attack and stroke.

Studies examining the relationship between dietary magnesium and lipid status have found dyslipidemia to be strongly related to low serum magnesium levels⁸, and have found that mineral supplementation including magnesium leads to significant improvements in lipid status²⁴. Very positive results have also been demonstrated in reducing platelet dependent thrombosis with magnesium supplementation, thereby significantly reducing risks for heart attacks and strokes^25-26. Schechter et. al.²⁵ found that platelet-dependent thrombosis was significantly inversely correlated with magnesium levels, and positively correlated with resting systolic blood pressure and total serum cholesterol. However, after statistical analysis, magnesium remained the only independent and significant predictor of platelet-dependent thrombosis.

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