MAGNESIUM METABOLISM IN DIABETES MELLITUS AND THE EFFECTS OF MAGNESIUM ADMINISTRATION ON PLASMA GLUCOSE AND INSULIN LEVELS

Abstract

Magnesium plays an important role in human metabolic activities. Its role in glucose metabolism is well established. However, there are still some conflicting views on the altered magnesium homeostasis in diabetic states and on the use of magnesium supplements in diabetic management. In this study, ionized plasma magnesium (the physiologically active form of blood magnesium) was measured in diabetic and non-diabetic subjects. Total plasma and erythrocyte magnesium were also determined in the two groups of subjects. Magnesium homeostatic studies were conducted during an oral glucose (75 gram) tolerance test and during an insulin (0.1 U/kg body weight) tolerance test in non-diabetic subjects. The effects of magnesium on plasma glucose and insulin levels were assessed by intravenous (15 mmol) and oral (30 mmol) magnesium administration to control subjects, while intravenous magnesium (15 mmol) was administered to diabetic subjects. The findings showed that ionized and total plasma magnesium were significantly lower in diabetics (NIDDM and IDDM combined) compared with non-diabetic control subjects (0.44 ± 0.01 vs 0.49 ± 0.01 mmo1/L; P< 0.01 and 0.80 ± 0.01 vs 0.87 ± 0.01; P< 0.001 respectively). The difference in total plasma magnesium was significant when non-diabetic control subjects were compared separately with IDDM subjects (0.79 ± 0.02 vs 0.88 ± 0.01 mmol/L; P<0.001). On the other hand, non-diabetic control subjects and NIDDM subjects had similar total plasma magnesium levels (0.81 ± 0.02 vs 0.86 ± 0.02mmol/L; P> 0.05). There was however no significant difference in erythrocyte magnesium levels in diabetic and non-diabetic control subjects (P> 0.05). During an oral glucose tolerance test (OGTT) in non-diabetic, non-obese subjects, an increase in blood glucose level resulted in an increase in both ionized (from 0.49 ± 0.01 to 0.51 ± 0.01; P< 0.05) and total (from 0.89 ± 0.01 to 0.92 ± 0.02; P< 0.05) plasma magnesium levels, but erythrocyte magnesium showed very little change (P>0.05). In obese subject after an oral glucose load (100g), there was an initial decrease in ionized plasma level (from 0.48 ± 0.01 to 0.46 ± 0.02 mmol/ L; P< 0.05). Total plasma magnesium level decreased slightly (from 0.93 ± 0.01 to 0.91 ± 0.01 mmol/L: p< 0.05), while there was a concomitant slight increase in erythrocyte magnesium level (from 2.14 ± 0.04 to 2.19 ± 0.05 mmol/L; p< 0.01). Intravenous insulin administration resulted in a decrease in total plasma magnesium level from 0.60 ± 0.01 to 0.55 ± 0.01 (P< 0.01) and an increase in erythrocyte magnesium level from 1.35 ± 0.04 to 1.45 ± 0.05 mmol/L (P<0.05). It was also established that non-insulin dependent diabetic subjects on insulin treatment for blood glucose control had raised ionized plasma magnesium concentration compared with those on oral hypoglycemic agents (0.47 ± 0.01 vs 0.42 ± 0.01 mmol/L; P< 0.05). Intravenous administration of magnesium resulted in a significant decrease in plasma glucose (from 4.78 ± 0.12 to 4.59 ± 0.12 mmol/L; P<0.05) and plasma insulin (from 8.50 ± 1.26 to 4.25 ± 1.02 uU/ml; P< 0.01) levels in non-diabetic subjects. It also resulted in a significant decrease in percentage B-cell response (from 134.3 ± 15.8 to 90.7 ± 15.8%; P< 0.01) and a significant increase in percentage insulin sensitivity (from 62.5 ± 13.9 to 166.8 ± 30.5 %; P<0.01). In the diabetic subjects following intravenous magnesium administration, plasma glucose decreased from 10.6 ± 1.16 to 6.8 ± 0.78 mmol/l (P<0.05), plasma insulin decreased from 14.6 ± 4.2 to 7.5 ± 2.8 uU/ml (P< 0.05) . On the other hand, percentage insulin sensitivity increased from 40.2 ± 14.2 to 93.3 ± 24.8 (P< 0.05), whereas there was no significant change in percentage B-cell response (P> 0.05). Oral magnesium administration to non-diabetic subjects, resulted in a decrease in plasma glucose level from 4.87 ± 0.11 to 4.39 ± 0.11 mmol/L (P< 0.001) and in plasma insulin levels from 8.75 ± 0.91 to 4.17 ± 0.61 uU/ml (P< 0.001). It also resulted in a significant increase in percentage insulin sensitivity from 52.4 to 8.5% to 133.0 ± 30.6 % (P<0.05) and a decrease in percentage B-cell response from 132.0 ± 11.5 to 96.2 ± 8.2 % (P< 0.01). Administration of magnesium to both groups of subjects does not appear to impair their renal function (P> 0.05). Diabetic patients showed a higher percentage retention of the intravenously administered magnesium (15 mmol) compared with non-obese, non-diabetics subjects (25.1 ± 2.4 vs 12.4 ± 4.1 %; P<0.05). The overall results suggest that magnesium depletion does occur in diabetes mellitus. Secondly, magnesium supplements may be beneficial in the control of blood glucose, but long term studies need to be done to confirm this.