Title: Diabetes and Micronutrients

Key words: Chromium, magnesium, copper, manganese, vanadium, zinc,

Date: March 1999

Category: 13. Specific Conditions

Type: Article

Author: Dr van Rhijn


Diabetes and Micronutrients


The mechanisms through which micronutrients participate in the pathogenesis and treatment of diabetes are still poorly understood. Research evidence indicates that several trace elements are essential for normal glucose homeostasis.



Chromium (Cr (III) forms an organic complex potentiating the action of insulin1, probably by optimising the membrane insulin receptors2, but the exact relationship is still obscure3. Chromium deficiency might lead to impaired glucose tolerance, insulin resistance4, hyperglycaemia and hypercholesterolaemia5. Chromium supplementation improved impaired glucose tolerance tests in subjects fed on low-chromium diets6 and had significant beneficial effects on HbA1c, glucose, insulin and cholesterol variables in subjects with Type 2 diabetes7, as well as showing a significant reduction in serum triglycerides (TG)8. Other studies have been unremarkable9, 10 or have produced inconsistent results11, 12. This may be due to the lower amount and different form of chromium consumed, rather than the 1000 m g/day of chromium picolate suggested as the most effective strength and form for supplementation13.


Diabetes mellitus is the chronic disease most frequently associated with secondary magnesium deficiency.

Hypomagnesaemia has been associated with insulin insensitivity, poor glycaemic control, retinopathy, hypertension and abnormal platelet function. This may be improved by oral supplementation14, 15. Intracellular magnesium may play a key role in modulating insulin-mediated glucose uptake and vascular tone, which might explain the epidemiological association between NIDDM and hypertension16. Studies suggest that hypermagnesiuria, due to a specific renal tubular magnesium defect, together with the osmotic diuresis, is responsible for large magnesium losses17. This may be a major factor in the reduced liver synthesis of certain serum proteins in diabetic children18. Magnesium (Mg2+) supplementation produced a significant reduction of plasma cholesterol and LDL cholesterol and an increase of HDL cholesterol 19.

Copper, Manganese and Vanadium

Several studies20, 21 have demonstrated that copper (Cu2+) deficiency can cause impaired glucose tolerance and decreased serum Cu levels. A higher Zn/Cu ratio was found in both forms of diabetes, but these changes were not related to chronic diabetic complications22. Manganese (Mn) activates SOD, puruvate kinase and a post-receptor kinase for insulin signalling. Deficiency of Mn is occasionally seen in diabetes, but Mn may also initiate hypoglycaemia. Although the normal biological role of vanadium is unknown, vanadium improves glucose control and sensitivity in models of diabetes, by improving hepatic glucose output, increasing peripheral insulin uptake 23 and reducing lipolysis. It is unclear if vanadium potentiates endogenous insulin, but it may act by inhibiting the phosphatases that normally de-phosphorylate the receptor and other kinases in the post-receptor signalling pathways for insulin.




Lower consumption of dietary zinc (Zn), even through drinking water24, and low serum Zn levels are associated with an increased prevalence of diabetes (Type I & II)25 and childhood onset diabetes. Diabetics have reduced intestinal Zn absorption and increased urine Zn elimination, but the mechanism of secondary insulin resistance remains unclear26. Although Zn supplementation seems to improve glucose tolerance in cirrhosis and the healing of venous leg ulcers27, the role of Zn in the management of diabetes, its complications and prevention is still poorly understood28.


The major problem with trace element studies is the accuracy of measurements and potential for error by contamination. Also, plasma levels do not always reflect intracellular levels and there are blurred boundaries between normality and deficiency. Many co-morbid conditions may cloud the already complex glucose homeostasis and it remains uncertain whether differences in trace element status are a consequence of diabetes, or alternatively, whether they contribute to the expression of the disease29.


Further investigation into the action and requirements of the micronutrients in diabetes are required before their significance in the pathogenesis in diabetes can be fully understood. There is enough evidence suggesting an association to merit routing serum screening for deficiencies. Supplementation may be appropriate, considering the low cost and safety profile of the trace elements, to aid glucose homeostasis and to ameliorate the long term complications of diabetes. Chromium is recommended, for example, by the American Diabetes Association30.



  1. Mertz, W. et al. Present knowledge of the role of chromium. Fedr. Proc. 1974;33: 2275 – 2280.
  2. Offenbach, E.G. & Pi-Sunyer, F.X. Chromium in human nutrition. Ann. Rev. of Nutr. 1998; 8: 543 – 563.
  3. Vitamins Minerals and Health: Fact File No 3: 1997; National Dairy Council. London.
  4. Mertz, W. Chromium in human nutrition: a review. J. of Nutr. 1993; 123, 626 – 633.
  5. Halliwell, B. & Gutteridge, J.M.C. Free Radicals in Biology and Medicine. Third Edition. Oxford University Press. 1999
  6. Anderson, R.A. et al. Supplemental chromium effects on glucose, insulin, glucagon and urinary chromium losses in subjects consuming low-chromium diets. Am. J. Clin. Nutr. 1991; 54: 909 – 916.
  7. Anderson, R.A. et al. Elevated Intakes of Supplemental Chromium improve Glucose and Insulin variables in individuals with Type 2 Diabetes. Diabetes. 1997; Vol. 46: 1786 - 1791.
  8. Lee, N.A. & Reasner, C.A. Beneficial effect of chromium supplementation on serum triglyceride levels in NIDDM. Diabetes Care. 1994; 17:12, 1449 - 1452.
  9. Ziegler, E. & Filer, L.J. Present knowledge in Nutrition. Seventh Edition. ILSI Press, Washington DC. 1996
  10. Uusitupa, M.I. et al. Chromium supplementation in impaired glucose tolerance of the elderly: effects on blood glucose, plasma insulin, C-peptide and lipid levels. B. J. Nutr. 1992; 68:1, 209 - 216.
  11. Garrow, J.S & James, W.P. Human nutrition and Dietetics. Ninth Edition. Churchill Livingstone. 1996
  12. Fox, G.N. & Sabovic, Z. Chromium picolinate supplementation for diabetes mellitus. J. Fam. Prac. 1998; 46:1, 83 - 86.
  13. Anderson, R.A. Chromium as an essential nutrient for humans. Regul. Toxicol. Pharmacol. 1997; 26:1 Pt 2, S35 - S41.
  14. American Diabetes Association Consensus Conference. Magnesium supplementation in the treatment of Diabetes mellitus. Diabetes Care. 1993; 16 (Suppl. 2): 1065 - 1067.
  15. Lima, M. et al. The effect of magnesium supplementation in increasing doses on the control of type 2 diabetes. Diabetes Care. 1998; 21:5, 682 - 686.
  16. Paolisso, G & Barbagallo, M. Hypertension, diabetes mellitus, and insulin resistance: the role of intracellular magnesium. Am. J. Hypertens. 1997; 10:3, 346 - 355.
  17. Garland, H.O. New experimental data on the relationship between diabetes mellitus and magnesium. Magnes. Res. 1992; 5:3, 193 - 202.
  18. Tuvemo, T. et al. Serum magnesium and protein concentrations during the first five years of insulin dependent diabetes in children. Acta. Paediatr. 1997; Suppl. 418: 7 - 10.
  19. Corica, F. et al. Effects of oral magnesium supplementation on plasma lipid concentrations in patients with non-insulin-dependent diabetes mellitus. Magnes. Res. 1994; 7:1, 43 - 47.
  20. Cohen, A.M. et al. Effects of copper on carbohydrate metabolism in rats. Isr. J. Med. Sci. 1982; 18(8): 840 – 844.
  21. Fields, M. et al. Impairment of glucose tolerance in copper-deficient rats : dependency on the type of carbohydrate. J. Nutr. 1984; 114(2): 393 – 397.
  22. Car, N. et al. Zinc and copper in the serum of diabetic patients. Biol. Trace Elem. Res. 1992; 32: 325 - 329.
  23. Cohen, N. et al. Oral Vanadyl Sulphate improves hepatic and peripheral insulin sensitivity in patients with Non-insulin dependent Diabetes Mellitus. J. Clin. Invest. 1995; 95: 2501 - 2509.
  24. Haglund, B. et al. Evidence of a relationship between childhood-onset type I diabetes and low groundwater concentration of zinc. Diabetes Care. 1996; 19:8, 873 - 875.
  25. Singh, R.B. et al. Current zinc intake and risk of diabetes and coronary heart disease and factors associated with insulin resistance in rural and urban populations of North India. J. Am. Coll. Nutr. 1998; 17:6,S64 - S70.
  26. Faure, P. et al. Zinc and insulin sensitivity. Biol. Trace. Elem. Res. 1992; 32: 305 -310.
  27. Franz.M.J. Nutrition Principles for the Management of Diabetes and Related Complications. Diabetes Care. 1994; 17: 490 - 518.
  28. Chausmer, A.B. Zinc, insulin and diabetes. J. Am. Coll. Nutr. 1998; 17:2. 109 - 115.
  29. Walter, R.M. et al. Copper, zinc, manganese, and magnesium status and complications of diabetes mellitus. Diabetes Care. 1991; 14:11, 1050 -1056.
  30. White, J.R. Magnesium and diabetes: a review. Ann. Pharmacother. 1993; 27:6, 775 - 780.