, Volume 36, Issue 8, pp 767–770 | Cite as

Intracellular and extracellular magnesium depletion in Type 2 (non-insulin-dependent) diabetes mellitus

  • L. M. Resnick
  • B. T. Altura
  • R. K. Gupta
  • J. H. Laragh
  • M. H. Alderman
  • B. M. Altura


To investigate alterations of magnesium metabolism in Type 2 (non-insulin-dependent) diabetes mellitus, we utilized a new magnesium-specific selective ion electrode apparatus to measure serum ionized magnesium (Mg-io) in fasting subjects with and without Type 2 diabetes, and compared these values to levels of serum total magnesium, and of intracellular free magnesium (Mgi) analysed by 31P-NMR spectroscopy. Both Mg-io (0.630±0.008 vs 0.552± 0.008 mmol/l, p<0.001) and Mgi (223.3±8.3 vs 184± 13.7 mmol/l,p<0.001), but not serum total magnesium, were significantly reduced in Type 2 diabetes compared with nondiabetic control subjects. Furthermore, a close relationship was observed between serum Mg-io and Mgi (r=0.728, p<0.001). We suggest that magnesium deficiency, both extracellular and intracellular, is a characteristic of chronic stable mild Type 2 diabetes, and as such, may predispose to the excess cardiovascular morbidity of the diabetic state. Furthermore, by more adequately reflecting cellular magnesium metabolism than total serum magnesium levels, Mg-io measurements may provide a more readily available tool than has heretofore been available to analyse magnesium metabolism in a variety of diseases.

Key words

Magnesium nuclear magnetic resonance spectroscopy Type 2 (non-insulin-dependent) diabetes mellitus erythrocytes ion selective electrode 


  1. 1.
    Aikawa J (1960) Effect of glucose and insulin on magnesium metabolism in rabbits. A study with magnesium-28. Proc Soc Exp Biol Med 103: 363–366Google Scholar
  2. 2.
    Atchley D, Loeb R, Richards D, Benedict E, Driscoll M (1933) On diabetic acidosis. A detailed study of electrolyte balances following the withdrawal and reestablishment of insulin therapy. J Clin Invest 12: 297–323Google Scholar
  3. 3.
    Nabarro J, Spencer A, Stowers J (1952) Metabolic studies in severe diabetic ketosis. Q J Med 21: 225–241Google Scholar
  4. 4.
    Rosner F, Gorfien P (1970) Zinc and magnesium levels in diabetes. JAMA 211: 2156Google Scholar
  5. 5.
    Stutzman F, Amatuzio D (1953) Blood serum magnesium in portal cirrhosis and diabetes mellitus. J Lab Clin Med 41: 215Google Scholar
  6. 6.
    Becket A, Lewis J (1959) Serum magnesium in diabetes. Clin Sci 18: 597Google Scholar
  7. 7.
    Altura B, Halevy S, Turlaplaty P (1979) Vascular smooth muscle in diabetes and its influence on the reactivity of blood vessels. Adv Microcirc 8: 118–150Google Scholar
  8. 8.
    Altura B, Altura B (1981) Magnesium ions and contraction of vascular smooth muscles: relationship to some vascular diseases. Fed Proc 40: 2672–2679Google Scholar
  9. 9.
    Chadda K, Gupta P (1972) Magnesium in cardiac arrhythmias. N Engl J Med 287: 1102Google Scholar
  10. 10.
    Kafka H, Langevin L, Armstrong P (1987) Serum magnesium and potassium in acute myocardial infarction: influence on ventricular arrhythmias. Arch Int Med 147: 465–469Google Scholar
  11. 11.
    Resnick L, Gupta R, Bhargava K, Gruenspan H, Alderman M, Laragh J (1991) Cellular ions in hypertension, diabetes, and obesity: a nuclear magnetic resonance spectroscopic study. Hypertension 17: 951–957Google Scholar
  12. 12.
    Resnick L, Gupta RK, Laragh JH (1984) Intracellular free magnesium in erythrocytes of essential hypertension: relation to blood pressure and serum divalent cations. Proc Natl Acad Sci USA 81: 6511–6515Google Scholar
  13. 13.
    Resnick L, Gupta R, Gruenspan H, Alderman M, Laragh J (1990) Hypertension and peripheral insulin resistance: mediating role of intracellular free magnesium. Am J Hypert 3: 373–379Google Scholar
  14. 14.
    Altura BT, Shirey TL, Hiti J, Tell'Orfano K, Hendwerker SM, Altura BM (1992) Characterization of a new ion selective electrode for ionized magnesium in whole blood, plasma, and serum. Methods Find Exp Clin Pharm 14: 297–304Google Scholar
  15. 15.
    Resnick L, Altura B, Altura B, Gupta R, Laragh J (1992) Serum ionized magnesium in essential hypertension and non-insulin dependent diabetes mellitus: relation to intracellular free magnesium. Clin Res 40: 438A (Abstract)Google Scholar
  16. 16.
    Resnick L (1989) Hypertension and abnormal glucose homeostasis: possible role of divalent ion metabolism. Am J Med 87 [Suppl 6 A]: 17S-22SGoogle Scholar
  17. 17.
    Gupta R, Benovic J, Rose J (1978) The determination of the free magnesium level in the human red blood cell by 31P-NMR. J Biol Chem 253: 6172–6176Google Scholar
  18. 18.
    Stephenson E, Podolsky R (1977) Regulation by magnesium of intracellular calcium movement in skinned muscle fibers. J Gen Physiol 69: 17–35Google Scholar
  19. 19.
    Flatman P, Lew V (1981) The magnesium dependence of sodium pump mediated sodium-potassium and sodium-sodium exchange in intact human red cells. J Physiol (Lond) 315: 421–446Google Scholar
  20. 20.
    Altura BM, Altura BT (1990) Magnesium and the cardiovascular system: experimental and clinical aspects updated. In: Sigel H, Sigel A (eds) Metal ions in biological system, vol 26. Marcel Dekker, New York, pp 359–416Google Scholar
  21. 21.
    Zahng A, Cheng T, Altura BT, Altura BM (1992) Extracellular magnesium regulates intracellular free Mg2+ in vascular smooth muscle cells. Pfuegers Arch 421: 391–393Google Scholar
  22. 22.
    Altura BM, Altura BT, Gebrewold A (1984) Magnesium deficiency and hypertension: correlation between magnesium-deficient diets and microcirculatory changes in situ. Science 223: 1315–1317Google Scholar
  23. 23.
    Johnson C, Peterson D, Smith E (1979) Tissue concentrations of magnesium and potassium in men dying of suddenly with ischemic heart disease. Am J Clin Nutr 32: 967–970Google Scholar
  24. 24.
    Stevenson M, Yoder L (1970) Studies of platelet aggregation, plasma ADP breakdown and blood coagulation in Mg deficient calves and rats. Thromb Diathes Haemorrh 23: 300–305Google Scholar
  25. 25.
    Nadler J, Malayan S, Luong H, Shaw S, Natarajan R, Rude R (1992) Evidence that intracellular free magnesium deficiency plays a key role in increased platelet reactivity in type II diabetes mellitus. Diabetes Care 15: 835–841Google Scholar
  26. 26.
    Huntsman R, Hurn B, Lehman H (1960) Observations on the effect of magnesium on blood coagulation. J Clin Pathol 13: 99–101Google Scholar
  27. 27.
    Altura B, Brust M, Bloom S, Barbour R, Stempack J, Altura B (1990) Magnesium dietary intake modulates blood lipid levels and atherogenesis. Proc Natl Acad Sci USA 87: 1840–1844Google Scholar

Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • L. M. Resnick
    • 1
    • 4
  • B. T. Altura
    • 2
  • R. K. Gupta
    • 3
  • J. H. Laragh
    • 1
  • M. H. Alderman
    • 3
  • B. M. Altura
    • 2
  1. 1.Cardiovascular CenterNew York Hospital-Cornell Medical CenterNew YorkUSA
  2. 2.Department of PhysiologyState University of New YorkBrooklynUSA
  3. 3.Departments of Epidemiology, Physiology and BiophysicsAlbert Einstein College of MedicineBronxUSA
  4. 4.Division of Endocrinology and HypertensionWayne State University Medical Center University Health Center-4HDetroitUSA

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