Trace elements in diabetes mellitus.
Mineral elements constitute a minute part of the living tissues. Yet, they are important for the vital processes of life. They were difficult to measure in the past. Hence, they were mentioned as occurring in traces and thus originated the term "trace elements". This term has persisted though they can now be estimated with great accuracy.
The importance of the trace elements in living organisms was first shown over a century ago. Claude Bernard and McMunn (Quoted by Lamb et al) demonstrated the existence of a number of trace-metal-containing enzymes (metalloenzymes) of importance to the structural and functional integrity of the living cells. Growing concern with environmental factors in human health over the last few years has aroused renewed interest in the trace elements. Abnormalities in their metabolism have been demonstrated in many human diseases. In particular, diabetes mellitus has been shown to be associated with abnormalities in the metabolism of zinc, chromium, magnesium and maganese.
Scott and Fischer first recognized the relationship between zinc and insulin. They found that whereas the normal human pancreas contained significant quantities of zinc, the diabetic pancreas contained very little. Later, the availability of histochemical techniques for the detection of zinc confirmed that zinc and insulin concentrations in the pancreas changed in the same direction in a variety of situations in humans. Organic compounds which were capable of reducing the zinc content of the pancreas were found to be diabetogenic in animal experiments.
Meltzer et al appear to be the first to have studied the urinary excretion of trace elements in diabetes mellitus. As a group, diabetics excrete more zinc in the urine than non-diabetics., ,  The mean plasma, leucocyte and erythrocyte zinc levels are significantly lower in diabetics than in non-diabetics. This has been challenged by other workers., ,  No correlation has been found between the plasma or urinary zinc levels on the one hand and the age at onset of diabetes, the patient's age or his weight, on the other.,
Some families excrete more zinc in the urine than others. Family studies suggest that zincuria could be under polygenic control. Urinary zinc excretion appears to be controlled by alleles at a number of loci and diabetics might possess a different assortment of these alleles as compared to non-diabetics.
The exact cause of hyperzincuria is not known. Disturbed metabolism of zinc metalloenzymes and abnormal binding of zinc to tissue proteins have been suggested as possible causes. The low plasma zinc levels in diabetics suggest that the hyperzincuria is of renal origin. Renal tubular defect in handling zinc and glucose-induced, osmotic diuresis are other possibilities.
The biological activity of chromium depends on its valency and the chemical form of the complex of which it is a part. Glucose tolerance factor (GTF) is a trivalent form of chromium that has high biological activity. GTF is a low molecular weight, soluble and dialysable organic compound.This is required for optimal glucose utilisation by the cells. That abnormalities in chromium metabolism exist in insulin dependent diabetics seems certain. Nanogram quantities of chromium are required in every insulin dependent system. It has been suggested that by acting on the ribosomes chromium facilitates the insulinstimulated aminoacid incorporation into protein.,  The glucose intolerance seen as age advances has been attributed to chromium deficiency, ,  If chromium administration can be shown to consistently correct the glucose intolerance of ageing, it might replace the use of the less physiological oral hypoglycemic agents in the treatment of this condition. Chromium is not a hypoglycemic agent in the usual pharmacological sense nor a substitute for insulin. It is a cofactor for the initiation of peripheral insulin action on the receptors on the cell membranes. , 
Insulin dependent diabetics excrete more chromium than the control subjects. However, there is no significant difference in the urinary excretion of chromium between maturity onset diabetics and normal controls Chromium deficiency has also been held responsible for vascular complications associated with diabetes mellitus. Increased incidence of aortic plaques has been shown in chromium deficient animals. Recent work has provided "Suggestive evidence for a relationship between certain body pools of chromium and carbohydrate metabolism in diabetes." Lastly, hyperglycemia occurring during total parenteral hyperalimentation has been shown to be controlled and insulin requirements reduced by oral administration of microgramme quantities of chromium.'
Magnesium is known to be related to the carbohydrate and fat metabolism. Serum magnesium levels have been shown to be inversely related to the severity of diabetes. Definite lowering of serum magnesium has been shown in patients on long term treatment with insulin and those recovering from diabetic ketoacidosis. The cause of this hypomagnesemia is not known for certain but the following have been suggested as possible mechanisms: (1) increased loss of magnesium in urine due to the osmotic action of glycosuria; and (2) depression of the net tubular reabsorption of magnesium due to hyperglycemia per se.
Magnesium may also play a role in the release of insulin. Magnesium depletion has an atherogenic potential.,  Hypomagnesemia has been postulated as a possible risk factor in the development and progression of diabetic retinopathy.,  Future research is called for to see if repletion of magnesium retards the progression of retinopathy. Patients with myocardial infarction had reversal of abnormal lipoprotein patterns to normal on administration of magnesium,  The Bantus have lower prevalence of I.H,D. and higher serum magnesium levels than the Europeans.Thus, magnesium may well have a local protective effect on the vessel well.
In experimental animals, pancreatectomy and diabetes have been correlated with decreased manganese levels in blood. Further, manganese supplements have reversed the impaired glucose utilization induced by manganese deficiency in guinea pigs.
It is thus seen that several abnormalities of trace metal metabolism have been demonstrated in diabetes mellitus, both human and experimental. Their pathogenetic implications and therapeutic applications must await further elucidation.