Association Between Serum Magnesium Levels and Glycemic Control in Type 2 Diabetes

Introduction

The prevalence of type 2 diabetes mellitus (T2DM) has emerged as a significant public health concern in China over recent decades.¹ Data from the International Diabetes Federation (IDF) reveals that China holds the world’s highest number of adult diabetic patients, totaling 140 million.² Concurrently, the market for drugs treating type 2 diabetes in China demonstrates a consistent upward trajectory. This trend reflects the growing awareness of diabetes, leading to an increase in patients seeking treatment. However, despite treatment, achieving optimal blood sugar control rates remains suboptimal.³ The American Diabetes Association (ADA) recommends a target glycosylated hemoglobin (HbA1c) level below 7% for diabetic patients lacking complications or previous hypoglycemic episodes.⁴

Serum magnesium is a vital mineral within the human body.⁵ Maintaining an appropriate serum magnesium level is crucial for diabetic patients, as it plays a significant role in glucose and insulin metabolism.⁶ Researches^7,8 indicate that low serum magnesium levels may contribute to insulin resistance and increase the risk of diabetes.

There is a recognized relationship between serum magnesium levels and T2DM. However, the majority of studies primarily examine dietary magnesium intake rather than serum magnesium levels, and their focus lies on its association with T2DM. Therefore, through examining the relationship between serum magnesium levels and fasting plasma glucose (FPG), HbA1c, body mass index (BMI), and visceral fat area (VFA) in individuals with T2DM, we can further understand the relationship between serum magnesium and glycemic control, as well as elucidate the impact of obesity on glycemic control.

Methods

Study Design and Participants

This retrospective, observational, cross-sectional study conducted at the People’s Hospital of Yuxi, Yunnan Province. The study data were collected from patients admitted to the Metabolic Management Center (MMC) between March 2018 and September 2023. This study received approval from the ethics committee of the Sixth Affiliated Hospital of Kunming Medical University (Approval No. 2024kmykdx6f003), adhering to the principles outlined in the Declaration of Helsinki. This retrospective analysis did not involve the collection of personal information from patients. Given that the exemption of informed consent would not adversely affect the rights or welfare of the subjects, we obtained approval for this exemption from the Ethics Committee.

The study included patients diagnosed with T2DM and a recorded serum magnesium level in their electronic medical records. Baseline information regarding patients’ lifestyle habits, dietary habits, demographics, and medications upon discharge was documented. Additionally, a series of laboratory tests were performed. The study excluded participants with prior diagnoses of type 1 diabetes and Other patients with non-T2DM, such as hyperthyroidism as determined by either medical records or the primary care physician’s diagnosis at baseline. Participants with missing data in laboratory tests or disease history were excluded. Finally, a total of 1694 patients were analyzed.

Measurements

Participants’ body weight and height were measured with them barefoot and wearing light clothing, and recorded to the nearest 0.1 kg and 0.1 cm, respectively. BMI was calculated using the formula weight (kg) divided by the square of height (m). Systolic and diastolic blood pressures (SBP/DBP) were measured twice using mercury sphygmomanometers following a 10-minute rest, and the average of the readings was recorded.

Blood samples were obtained via venipuncture after fasting. The serum samples were allowed to clot and then centrifuged at 5000 rpm for 10 minutes. FPG levels were determined using the hexokinase method. HbA1c levels were measured using high-performance liquid chromatography. Total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL-C), and low-density lipoprotein (LDL-C) levels were measured using enzymatic methods. Plasma insulin concentration was assessed using a chemiluminescence-based assay. The homeostasis model assessment of insulin resistance (HOMA-IR) index was calculated using the formula: fasting insulin × fasting glucose/22.5.⁹ Serum magnesium concentrations were determined using the colorimetric method. VFA was measured in cm² using the DUALSCAN device.

Definitions

Patients were categorized into two groups based on their HbA1c levels: good glycemic control (HbA1c < 7%) and poor glycemic control (HbA1c ≥ 7%).⁴ BMI categories were defined as follows: normal (18.5 ≤ BMI < 24), overweight (24 ≤ BMI < 28), and obese (BMI ≥ 28) according to the China Working Group on Obesity guidelines.¹⁰ Visceral obesity was defined as VFA of 100 cm² or greater.¹¹

Statistical Analysis

Data are presented as mean ± standard deviation (SD). Chi-square tests were employed to compare categorical variables, presenting results as percentages. Correlation analysis was utilized to assess associations between variables. Pearson’s correlation coefficients were calculated to measure the strength and direction of relationships between variables. Additionally, a correlation matrix diagram was generated. Logistic regression analysis was conducted to assess the association between variables and the quality of glycemic control. Linear regression analysis was performed to evaluate the relationship between serum magnesium levels and HbA1c. P < 0.05 was considered significant. All the analyses were performed with the statistical software packages R (http://www.R-project.org, The R Foundation).

Results

Baseline Characteristics

The retrospective study comprised 1694 patients, with a male-to-female ratio of 63.8% to 36.2% and a mean age of 54.3 ± 11.1 years. Of these, 247 patients exhibited good glycemic control, while 1447 patients had poor glycemic control. Patients with poor glycemic control exhibited higher age, LDL-C, FPG, and HOMA-IR levels compared to those with good glycemic control (P < 0.001). Additionally, TC levels were significantly higher in patients with poor glycemic control. Conversely, HDL-C and serum magnesium levels were lower in patients with poor glycemic control. Interestingly, no significant differences were observed in BMI and VFA between the two groups. However, when grouped according to their respective standards, significant differences were observed (P < 0.05) (Table 1).

Table 1 Comparison of Basic Characteristics

Association of Serum Magnesium Levels with Glycaemic Control

In the correlation matrix diagram, the correlation matrix revealed negative correlations between serum magnesium levels and HOMA-IR (r = −0.05, P < 0.05), HbA1c (r = −0.29, P < 0.05), and FPG (r = −0.20, P < 0.05) (Figure 1). A linear regression curve was used to estimate the correlation between serum magnesium levels and HbA1c, revealing that serum magnesium levels decrease with increasing HbA1c (Figure 2). A logistic regression analysis was conducted to estimate the independent contribution of variables to the risk of poor glycemic control. The analysis revealed a significant association between serum magnesium levels and reduced odds of glycemic control (OR = 0.0005, 95% CI 0.0001–0.0027, P < 0.001). Additionally, age, BMI, TC, TG, HDL-C, LDL-C, FPG, and VFA demonstrated associations with glycaemic control (P < 0.05) (Table 2).

Table 2 Logistic Regression Analysis for Whether Glycaemic Control is Well

Figure 1 Correlation coefficients between the varies. *P values <0.05.

Figure 2 Association between HbA1c and serum magnesium.

Discussion

In this study, we found a correlation between serum magnesium levels and glycemic control, indicating that serum magnesium levels decrease with increasing HbA1c. Furthermore, correlation analysis indicated associations between magnesium levels and FPG, as well as HbA1c, but not with BMI and VFA. This suggests that to enhance magnesium levels and decrease the occurrence of hypomagnesemia, emphasis should be on glycemic control rather than weight loss.

Magnesium homeostasis is tightly regulated and depends on the balance between intestinal absorption and renal excretion.¹² Additionally, when serum magnesium concentration decreases, magnesium stored in bones can be released into the blood to compensate for the deficiency.¹³ The mechanisms underlying the association between T2DM and low serum magnesium levels remain incompletely understood. Gender has little direct influence on serum magnesium level, and the results of this study also prove this statement. With the increase of age, the absorption and utilization ability of magnesium may gradually decline, and at the same time, due to the weakening of metabolic function, blood sugar control may be more difficult. Some studies^14,15 suggested that hyperglycemia in T2DM increases the glomerular filtration rate, leading to inadequate magnesium reabsorption in renal tubules, resulting in elevated urinary magnesium excretion and decreased serum magnesium concentration. Furthermore, a study¹⁶ in pre-diabetes indicated that increased renal magnesium consumption due to uncontrolled diabetes may contribute to low serum magnesium levels. Moreover, it has been suggested that insulin resistance may disrupt the absorption and utilization of magnesium ions, contributing to low serum magnesium levels. This is because the primary site of magnesium absorption is the small intestine.¹⁷ Insulin resistance may induce inflammation and oxidative stress,¹⁸ damaging the mucosa of the small intestine and impairing its absorption function.¹⁹ Thus, while magnesium excretion was not directly measured in this study, the elevated urinary magnesium loss may account for the observed low serum magnesium concentration in T2DM patients with poor glycemic control.

Our study revealed no correlation between BMI, VFA, and serum magnesium levels. While many studies²⁰ have linked glucose levels with obesity, it is important to note that obesity can contribute to hyperglycemia to some extent. However, it has been observed that low magnesium levels in obese individuals are associated with diabetes and glycemic control, rather than obesity itself.²¹ Similarly, Li et al demonstrated that there was no difference in BMI among magnesium quintiles.⁹ Additionally, some studies¹⁶ have demonstrated that the impact of serum magnesium on the risk of pre-diabetes and diabetes is partially mediated by insulin resistance. Therefore, while weight loss is crucial for improving the overall health of patients with T2DM, controlling glucose levels may be the primary consideration in preventing hypomagnesemia. In general, maintaining good glycemic control is crucial for patients with T2DM. This can help prevent hypomagnesemia, as well as slow the progression of the disease and improve quality of life.

Several potential limitations need consideration when evaluating our study results. First, we did not assess daily magnesium intake. This limitation arises from the retrospective nature of our research, making it impractical to effectively follow up with every patient. This study relies on previously collected case information, which in some instances is incomplete, particularly concerning drug use, lifestyle, and comorbidities. Therefore, in future research, we will enhance the collection of participants’ personal information and expand the sample size. Additionally, the imbalance in the number of subjects with good and poor glycemic control, stemming from the majority seeking hospitalization due to poor glycemic control, limited our ability to achieve parity between the groups. Lastly, we did not analyze the relationship between serum magnesium and insulin resistance as in other studies, primarily due to the absence of non-diabetic individuals as controls, despite calculating HOMA-IR. However, investigating this relationship will be a focus of our future research.

Conclusion

In patients with T2DM, serum magnesium levels are closely associated with glycemic control. Prioritizing glycemic control over weight loss is essential for reducing the incidence of hypomagnesemia.