Hypomagnesemia in Type 2 Diabetes: A Vicious Circle?

Diabetes. 2016 Jan;65(1):3-13. doi: 10.2337/db15-1028.


Over the past decades, hypomagnesemia (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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Blood Glucose / metabolism
  • Calcium Channels, L-Type / metabolism
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / metabolism*
  • Dietary Supplements
  • Disease Progression
  • Glucokinase / metabolism
  • Glycogen / biosynthesis
  • Glycolysis
  • Humans
  • Inflammation
  • Insulin / metabolism
  • Insulin Resistance
  • Insulin Secretion
  • Insulin-Secreting Cells / metabolism
  • KATP Channels / metabolism
  • Liver / metabolism
  • Magnesium / metabolism*
  • Magnesium / therapeutic use
  • Magnesium Deficiency / drug therapy
  • Magnesium Deficiency / metabolism*
  • Obesity / metabolism
  • Potassium Channels, Inwardly Rectifying / metabolism
  • Sodium Chloride Symporters / metabolism
  • Sodium-Potassium-Exchanging ATPase / metabolism
  • Water-Electrolyte Imbalance / drug therapy
  • Water-Electrolyte Imbalance / metabolism*


  • Blood Glucose
  • Calcium Channels, L-Type
  • Insulin
  • KATP Channels
  • Kcnj10 (channel)
  • Potassium Channels, Inwardly Rectifying
  • Sodium Chloride Symporters
  • Glycogen
  • Glucokinase
  • Sodium-Potassium-Exchanging ATPase
  • Magnesium