title: Intracellular free magnesium deficiency plays a key role in increased platelet reactivity in type II diabetes mellitus.
abstract: OBJECTIVE
  Mg deficiency may be an important factor leading to cardiovascular disease. Diabetic subjects show an increase in platelet reactivity that can enhance the risks of vascular disease. In addition, diabetic patients have been reported to be at risk of developing extracellular Mg deficiency. However, the intracellular free Mg concentration and its role in the enhanced platelet reactivity in diabetes is not known.
  
  
  METHODS
  We evaluated the intracellular erythrocyte (RBC) Mg2+ concentration in 20 non-insulin-dependent (type II) diabetics. In addition, the effects of intravenous 3-h drip or 8 wk of oral Mg supplementation on intracellular RBC Mg2+ levels and platelet reactivity was studied. To more clearly evaluate the direct role of Mg in these effects, we induced isolated Mg deficiency in 16 nondiabetic control subjects with an Mg-free liquid diet for 3 wk.
  
  
  RESULTS
  The intracellular RBC Mg2+ concentration of diabetic patients was significantly reduced compared with values in nondiabetic control subjects (166 +/- 7 vs. 204 +/- 7 microM, P less than 0.01). Serum Mg levels were also reduced in the diabetic patients compared with the control subjects (1.59 +/- 0.04 vs. 1.9 +/- 0.1 mEq/L, P less than 0.05). Oral Mg supplementation for 8 wk (400 mg/day) restored RBC Mg2+ concentration to normal without significantly changing serum Mg concentration. Both intravenous and oral Mg supplementation markedly reduced platelet reactivity in response to the thromboxane A2 analog, U46619. The Mg-free diet resulted in a significant reduction in RBC Mg2+ concentration and markedly enhanced the sensitivity of platelet aggregation to U46619 and ADP.
  
  
  CONCLUSIONS
  These results suggest that type II diabetic patients have intracellular Mg2+ deficiency and that Mg deficiency may be a key factor in leading to enhanced platelet reactivity in type II diabetes. Therefore, Mg supplementation may provide a new therapeutic approach to reducing vascular disease in patients with diabetes.
authors.affiliation: Department of Diabetes, Endocrinology and Metabolism, City of Hope National Medical Center, Duarte, California 91010.
authors.forename: J L
authors.initials: JL
authors.lastname: Nadler
authors.forename: S
authors.initials: S
authors.lastname: Malayan
authors.forename: H
authors.initials: H
authors.lastname: Luong
authors.forename: S
authors.initials: S
authors.lastname: Shaw
authors.forename: R D
authors.initials: RD
authors.lastname: Natarajan
authors.forename: R K
authors.initials: RK
authors.lastname: Rude
mesh_terms: D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000502:physiology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D006801:Humans; D008275:Magnesium Deficiency / Q000097:blood / Q000150:complications*; D008297:Male; D008875:Middle Aged