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 HbA_1c, 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 unremarkable^{9, 10} or have produced inconsistent results^{11, 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 supplementation^{14, 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.

Several studies^{20, 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.