Over the past decades, hypomagnesemia (deficiency of magnesium in the blood) (serum Mg(2+) <0.7 mmol/L) has been strongly associated with type 2 diabetes mellitus (T2DM). Patients with hypomagnesemia show a more rapid disease progression and have an increased risk for diabetes complications.
Clinical studies demonstrate that T2DM patients with hypomagnesemia have reduced pancreatic β-cell activity and are more insulin resistant. Moreover, dietary Mg(2+) supplementation for patients with T2DM improves glucose metabolism and insulin sensitivity.
Intracellular Mg(2+) regulates glucokinase, KATP channels, and L-type Ca(2+) channels in pancreatic β-cells, preceding insulin secretion. Moreover, insulin receptor autophosphorylation is dependent on intracellular Mg(2+) concentrations, making Mg(2+) a direct factor in the development of insulin resistance.
Conversely, insulin is an important regulator of Mg(2+) homeostasis. In the kidney, insulin activates the renal Mg(2+) channel transient receptor potential melastatin type 6 that determines the final urinary Mg(2+) excretion. Consequently, patients with T2DM and hypomagnesemia enter a vicious circle in which hypomagnesemia causes insulin resistance and insulin resistance reduces serum Mg(2+) concentrations. This Perspective provides a systematic overview of the molecular mechanisms underlying the effects of Mg(2+) on insulin secretion and insulin signaling. In addition to providing a review of current knowledge, we provide novel directions for future research and identify previously neglected contributors to hypomagnesemia in T2DM.
Gommers LM1, Hoenderop JG1, Bindels RJ1, de Baaij JH2. “Hypomagnesemia in Type 2 Diabetes: A Vicious Circle?” Diabetes. 2016 Jan;65(1):3-13. doi: 10.2337/db15-1028.
© 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
Andrea G. Scott, PharmD, MPHPharmacist, Johnston Willis Hospital, Midlothian, Virginia
“Magnesium and insulin have a reciprocal relationship. Insulin helps regulate the transport of magnesium cation from the extracellular to intracellular space for use in glucose metabolism. As part of glucose metabolism, magnesium promotes many of the enzymatic reactions in glycolysis. Magnesium deficiency causes insulin resistance, that is, more insulin than normal is required to metabolize glucose. As a result, the presence of hypomagnesemia and glucose intolerance can feed a comorbid (co-occurring with a primary disease or disorder) cycle of insulin resistance caused by hypomagnesemia and reduced serum magnesium caused by insulin resistance. (See Study Abstract Above) Hypomagnesemia is a common laboratory abnormality in patients with type 2 diabetes, suggesting that increasing magnesium intake could be beneficial for glucose control.”
Carolyn Dean, MD, ND
Although doctors seem reluctant to admit it, according to magnesium researchers in this review paper “Over the past decades, hypomagnesemia has been strongly associated with type 2 diabetes.” Also if magnesium is low the disease progresses rapidly and there is an increased risk for complications. The list continues – patients with hypomagnesemia have reduced pancreatic β-cell activity and are more insulin resistant. Therapeutically, Moreover, dietary supplementation with magnesium improves glucose metabolism and insulin sensitivity. The many attributes of magnesium include: regulation of glucokinase, KATP channels, and L-type Ca(2+) channels in pancreatic β-cells, preceding insulin secretion. Also the necessary addition of phosphorous to insulin receptors depends on magnesium, making it a direct factor in the development of insulin resistance. This is not just a one-way relationship, however because insulin is an important regulator of magnesium ion homeostasis. In the kidney, insulin activates the renal magnesium channels that determine how much urinary magnesium is excreted. As a result, patients with type 2 diabetes and hypomagnesemia enter a vicious circle in which hypomagnesemia causes insulin resistance and insulin resistance reduces serum magnesium concentrations. The paper ends by providing “novel directions for future research and to identify previously neglected contributors to hypomagnesemia.”
At the NMA we say that there is more than enough evidence to give a blanket recommendation to people with type 2 diabetes to supplement with magnesium.