Hypomagnesemia and Type2 Diabetes Mellitus: A Review of the Literature

Review Article

Austin J Nutri Food Sci. 2014;2(4): 1025.

Hypomagnesemia and Type2 Diabetes Mellitus: A Review of the Literature

Bishwajit Ghose1* and Seydou Ide2

1Institute of Nutrition and Food Science, University of Dhaka, Bangladesh

2Faculty of Health Sciences, University of Ottawa, Canada

*Corresponding author: :Institute of Nutrition and Food Science, University of Dhaka, Bangladesh

Received: February 20, 2014; Accepted: March 24, 2014; Published: April 02, 2014

Abstract

Globally, diabetes Mellitus is the most prevalent disease among all race and ethnicities, and hence attaches extraordinary medical importance. The body of medical literature studying both macro and micro nutrients in regard to their association with diabetes has been growing continuously making it one of the most widely studied medical complication. The study of trace elements is a branch of diabetes literature that is considered vital due to their links to the aetiology and consequences of the disease. Mg is one of the trace elements that has enjoyed numerous experiments owing to its to its involvement with insulin sensitivity and carbohydrate metabolism and other vital physiological functions. As more and more researches are being carried out, its important to stay updated with the most recent research outcomes. The volume of studies on diabetes is overwhelmingly large and continues to grow. But the result remain mixed to some extent. This review aims to provide 1) a most recent epidemiologic evidence on the correlation between Mg and diabetes mellitus based on the researches that have been carried out on this topic so far. 2) and the potential benefits of Mg repletion in hypomagnesemic patients with DM.

Method: The Medline and Embase database were searched for publications between January 1989 and December 2013, using the following search termdiabetes, trace elements, Mg, insulin sensitivity, causes of Mg deficiency, dietary supplement, oral solution. No language restriction was applied. The original articles were selected manually and only human clinical studies were selected for this review.

Conclusions: Hypomagnesemia occur at an increased frequency among patients with type 2 diabetes. There exists a positive link between hypomagnesemia and hyperglycemia. The cause of diabetic hypomagnesemia is multifactorial and diabetic patients have significantly lower mean serum Mg levels compared with healthy counterparts.

Keywords: Magnesium; Insulin resistance; Type 2 diabetes; Hypomagnesemia; Dietary management.

Abbreviations

NIDDM: Non–insulin Dependent Diabetes Mellituss; RDI: Recommended Dietary Allowance; TNF: Tumor Necrosis Factor.

Introduction

Mg is the second most abundant intracellular cation and is involved in numerous enzymatic pathways including those of glucose metabolism. Less than 1% of the total body Mg is present in blood, one–third as protein bound, and two–third in ionized form; thus serum Mg does not provide reliable information about total or intracellular magnesium concentration [1]. Intracellular Mg plays a key role in regulating insulin action, insulin–mediated–glucose uptake and vascular tone. Small intestine is the main site for Mg absorption, whereas Mg excretion is mainly performed through renal pathways. It is a vital cofactor for many enzymatic reactions and a key player in glucose metabolism and insulin homeostasis. Diabetes mellitus is a serious chronic metabolic disorder that has a significant impact on the health, quality of life, and life expectancy of patients, as well as on the health care system. There is accumulating evidence that the changes which occur in the metabolism of some micronutrients in diabetes mellitus might have a specific role in the pathogenesis and complications of this disease [2]. Several minerals have been found to benefit people with diabetes, either because they help to cope up with the risk factors, or because of the beneficial effect on glucose metabolism. Amongst the most important minerals for supplementation are chromium, magnesium, and vanadium [3]. There exists a complex interplay between Mg and carbohydrate metabolism. Mg deficiency is the most evident disturbance of metal metabolism in insulin–dependent diabetes mellitus. Hypomagnesemia has been linked both to the acute metabolic and late chronic complication of diabetes. Mg levels can become low due to low dietary intake, poor ingestion, increased urinary loss. Studies have shown that Mg levels are lower in patients with diabetes compared with nondiabetic controls [4,7,8,14].

Diabetes is a also key factor accounting for the low serum Mg levels. Diabetes once diagnosed is for life and exercise, diet, and weight control continue to be essential and effective means of improving glucose homeostasis. As hypomagnesemia is frequently present in diabetic patients, increasing dietary intake and supplement is also prescribed routinely. Diet is widely believed to play an important role in the development of type 2 diabetes [12]. Mg is involved with carbohydrate metabolism and has beneficial effects in the action of insulin [1]. A number of prospective cohort studies of Mg intakeand diabetes incidence have been conducted, but the results remain mixed.

Hypomagnesemia in Type 2 diabetes mellitus: Symptomatic Mg depletion is often associated with multiple biochemical abnormalities such as hypokalemia, hypocalcemia, and metabolic alkalosis [39]. Hypomagnesemia is defined as a plasma total Mg concentration lower than 0.7 mmol⁄L. Mg (Mg) is primarily found within the cell, where it is a metallic cofactor for over 300 enzymatic reactions involved inprotein and nucleic acid synthesis and in energy metabolism [12]. Body Mg homeostasis is very strictly regulated and balanced by intestinal absorption and renal excretion. The levels of Mg in the plasma of healthy people are extremely constant, with a reference interval for total serum levels of 0.75-0.96 mmol⁄L, and a mean of 0.85 mmol⁄L [37].The association of hypomagnesemia and insulin resistance in diabetes patients has been documented previously. Hypomagnesemia occurs at an incidence of 13.5 to 47.7% among patients with type 2 diabetes [38].

According to popular hypothesis, low serum Mg affects diabetes through modulating insulin activity. Figure 1 illustrates a conceptual framework of the link between Mg and NIDDM(Non–insulin dependent diabetes mellitus). Diabetes is frequently associated withboth extracellular and intracellular Mg depletion. Epidemiologic studies have found a high prevalence of hypomagnesaemia in subjects with type 2 diabetes, especially in those with poorly controlled glycemic control. Cross sectional studies on diabetic patients showed lower serum Mg concentrations in comparison with non–diabetic patients [22]. Hyperinsulinemia per se may also contribute to the urinary Mg depletion [36]. Since serum Mg levels have been related to high blood pressure and oxidative stress which are risk factors of diabetes, hypomagnesemia can induce development of type 2 diabetes by affecting those risk factors. Hypomagnesemia was also associated with poorer glycemic control and nephropathy [25]. According to a case–control study on 200 obese subjects, type 2 diabetes was found to be the main factor accounting for the low serum Mg levels in morbidly obese subjects [22]. Hypomagnesemia is therefore both, a contributing factor for development of type 2 diabetes and also involved in low Mg levels in the diabetic patients.

Mg and insulin activity: Diabetes mellitus, one of the chronic diseases, is most frequently associated with Mg deficiency [6]. The relationship between insulin and Mg is a complex one. Insulin regulates Mg homeostasis but, in turn, Mg itself is a major determinant of insulin and glucose metabolism.. Insulin resistance is a major risk factor for type 2 diabetes and various other metabolic disorders. Diabetes mellitus is a metabolic disorder of multiple etiology characterized by chronic hyperglycemia with disturbances of macronutrients metabolism resulting from defects in insulin secretion, insulin action, or both. Mg is an essential cofactor for multiple enzymes involved in glucose metabolism and is hypothesized to play a role in glucose homeostasis, insulin action and in the developmentof type 2 diabetes [4-6]. Mg plays an important role in glucose homeostasis and is involved in glucose homeostasis at multiple levels.