Discussion
diarrhoea, muscle cramps, Muscle cramps, gastrointestinal side-effects, intestinal loss, hypomagnesaemia, type 2 diabetes, insulin-treated type 2 diabetes
ADVERSE EFFECTS, HYPOMAGNESAEMIA, TYPE 2 DIABETES, INSULIN SENSITIVITY
The main finding of this study is that oral magnesium supplementation, despite significantly increasing the serum magnesium concentration, did not improve insulin sensitivity in people with insulin-treated type 2 diabetes and low magnesium levels. Furthermore, during the 6 week treatment periods, magnesium supplementation did not improve variables of glucose control, insulin need, lipid profile or BP and had no effect on hypomagnesaemia-related symptoms. These results do not support magnesium supplementation to people with insulin-treated type 2 diabetes and a low serum magnesium concentration.Oral magnesium supplementation increased serum magnesium by a mean of 0.05 mmol/l in our study participants, which is in line with previous reports [While we can only compare the insulin sensitivity between the two study arms, comparison with literature [In our study, magnesium supplementation did not improve glucose control, which is in line with unaltered insulin sensitivity and insulin dose. The study duration may have been too short to show an effect on HbAPrevious studies reported improvements in BP and lipids after magnesium supplementation but our study might have been too short and underpowered for these outcomes [In exploratory analyses, we found that despite strong beliefs, hypomagnesaemia-related symptoms were similar after magnesium and placebo treatment and there was no correlation between the change in magnesium level and change in symptom frequency and severity. Low potassium and calcium levels produce symptoms similar to those of hypomagnesaemia and are often simultaneously present, but both were within normal ranges in our participants. Muscle cramps are the most abundant symptom caused by hypomagnesaemia but meta-analyses data show inconsistent results regarding the effect of magnesium supplementation on muscle cramps in people not necessarily selected for a low magnesium concentration [Strengths of our study are the randomised, placebo-controlled, double-blind, crossover design, the use of the glucose clamp technique, which is the gold standard for measuring insulin sensitivity, and the inclusion of a study population that was found to be clearly insulin resistant and therefore most likely to benefit to the greatest extent from improvements in insulin sensitivity.Our study also has limitations. First, we have no registration of the diet of the participants, although we do not expect a change in eating habits during the study period, especially because the occurrence of gastrointestinal side-effects was evenly distributed among the two treatments. Besides, dietary records often include bias and because we found an increase in serum magnesium after supplementation, reporting dietary magnesium intake becomes less important. Furthermore, variables potentially affecting insulin sensitivity such as body weight, physical activity and glucose control, all objectively measured, did not differ between the study arms. Second, while magnesium levels increased significantly, the increase was relatively modest and participants remained at the low end of the normal range. Although serum magnesium is generally accepted to reflect the overall magnesium status, we have no information on the intracellular magnesium concentration. Our study does not exclude the possibility that supplementation to higher magnesium levels could have a positive effect on insulin sensitivity in this population. However, as discussed above, oral supplementation to higher levels may not be possible due to adverse effects with higher dosing, including diarrhoea that may promote intestinal loss of magnesium, and the possible concomitant greater urinary excretion of magnesium. Third, we cannot generalise our results to people with type 2 diabetes and poorer glucose control or to those with a higher baseline serum magnesium concentration, as is the case for the majority of people with type 2 diabetes [In conclusion, oral magnesium supplementation does not improve insulin sensitivity in people with insulin-treated type 2 diabetes and a low magnesium level, neither does it affect glucose control, lipid profile, BP and hypomagnesaemia-related symptoms. Therefore, our trial does not support routine use of magnesium supplementation in people with insulin-treated type 2 diabetes.