Oral magnesium supplementation improves glycaemic status in subjects with prediabetes and hypomagnesaemia: A double-blind placebo-controlled randomized trial

Abstract

Aim

This study evaluated the efficacy of oral magnesium supplementation in the reduction of plasma glucose levels in adults with prediabetes and hypomagnesaemia.

Methods

A total of 116 men and non-pregnant women, aged 30 to 65 years with hypomagnesaemia and newly diagnosed with prediabetes, were enrolled into a randomized double-blind placebo-controlled trial to receive either 30 mL of MgCl₂ 5% solution (equivalent to 382 mg of magnesium) or an inert placebo solution once daily for four months. The primary trial endpoint was the efficacy of magnesium supplementation in reducing plasma glucose levels.

Results

At baseline, there were no significant statistical differences in terms of anthropometric and biochemical variables between individuals in the supplement and placebo groups. At the end of follow-up, fasting (86.9 ± 7.9 and 98.3 ± 4.6 mg/dL, respectively; P = 0.004) and post-load glucose (124.7 ± 33.4 and 136.7 ± 23.9 mg/dL, respectively; P = 0.03) levels, HOMA-IR indices (2.85 ± 1.0 and 4.1 ± 2.7, respectively; P = 0.04) and triglycerides (166.4 ± 90.6 and 227.0 ± 89.7, respectively; P = 0.009) were significantly decreased, whereas HDL cholesterol (45.6 ± 10.9 and 46.8 ± 9.2 mg/dL, respectively; P = 0.04) and serum magnesium (1.96 ± 0.27 and 1.60 ± 0.26 mg/dL, respectively; P = 0.005) levels were significantly increased in those taking MgCl₂ compared with the controls. A total of 34 (29.4%) people improved their glucose status (50.8% and 7.0% in the magnesium and placebo groups, respectively; P < 0.0005).

Conclusion

Our results show that magnesium supplementation reduces plasma glucose levels, and improves the glycaemic status of adults with prediabetes and hypomagnesaemia.

Introduction

Lifestyle changes related to globalization have resulted in remarkable changes in human behaviour and increased the number of obese people, with a consequent increase in the incidence and prevalence of type 2 diabetes (T2D). Thus, the disorder ranks high on the international agenda as a global pandemic threat to human health and the global economy [1].

It is well known that, in the natural history of T2D, the development of insulin resistance is among the early underlying mechanisms and that normal glucose tolerance shows a gradual impairment that mirrors the failure of beta-cell function to compensate for the increased insulin resistance. There are also pathophysiological mechanisms that lead to prediabetic hyperglycaemic states, defined as the presence of impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), or both.

Although not all prediabetic individuals progress to diabetes, identification of prediabetes provides an opportunity for early interventions to prevent or delay the progression of disease [2], thus supporting the hypothesis that the natural history of diabetes can be changed through routine screening combined with management aimed at keeping glucose levels as close to normal as possible [3].

The above-mentioned hypothesis is of particular importance when taking into account the study by Danaei et al. [4], which analyzed data from 2.7 million adults participating in health surveys and epidemiological studies worldwide, and showed rising glycaemic levels in the populations of developed and developing countries, resulting in the increase in rates of prediabetes.

Magnesium is an essential cofactor in the enzymatic processes of the high-energy phosphate and glucose metabolic pathways [5], [6], [7] involved in the development of hyperglycaemia. With this in mind, low serum magnesium levels in individuals with prediabetes are significantly lower than in those with normal glucose tolerance [8]. In addition, it has been shown that oral magnesium supplementation reduces insulin resistance and improves beta-cell function to compensate for variations in insulin sensitivity [9], [10].

Although several trials have demonstrated that an increase of magnesium intake with the customary diet reduces the risk of impaired glucose and the progression of prediabetes to diabetes [11], [12], there are no reports based on randomized controlled clinical trials evaluating the role of magnesium supplementation in the improvement of prediabetes. Yet, such an approach could be of particular importance, given that foods containing magnesium (unprocessed foods such as whole grains, nuts and green leafy vegetables) are uncommon in Westernized diets. Thus, the objective of the present study was to evaluate the efficacy of oral magnesium supplementation in reducing plasma glucose in individuals with prediabetes and hypomagnesaemia.