Abstract
OBJECTIVE
The role of magnesium in glucose homeostasis, its effects on glycemic control and the causal relationship between them have been the subject of many studies. In this direction, in our study, we aimed to investigate the relationship between serum magnesium (Mg) levels and hemoglobin A1c (HbA1c) and insulin resistance.
METHODS
Based on their HbA1c levels, 305 participants were split into 3 groups: 121 were in the control group, 85 were in the prediabetes group, and 99 were in the diabetes group. Serum magnesium levels were measured in these three groups. The correlation between Mg and fasting plasma glucose, fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR) was also investigated. In addition, patients’ demographic data, blood pressure, smoking habits and basic biochemical data were also included in the analysis.
RESULTS
There was a significant statistical difference in terms of serum magnesium levels among all the groups (p<0.001). A strong negative correlation was found between serum magnesium levels and HbA1c (r=-0.316, p<0.001). There was also a weak negative relationship between Mg and serum fasting glucose, insulin, and HOMA-IR (r=-0.167 p=0.004, r=-0.167 p=0.003, and r=-0.198 p=0.001, respectively).
CONCLUSION
We observed a statistically significant negative correlation between serum magnesium levels and HbA1c in our study. According to this finding, it would be useful to assess magnesium levels in patients with high HbA1c levels. However, due to conflicting results among studies investigating the relationship between magnesium, glycemic control and insulin sensitivity with increasing interest, more comprehensive, prospective studies with longer follow-up periods are needed.
Keywords: Diabetes mellitus, glycemic control, hemoglobin A1c, insulin resistance, magnesium
Highlight key points
A statistically significant negative correlation was found between serum magnesium levels and HbA1c, indicating that lower magnesium levels are associated with poorer glycemic control.
Weak inverse correlations were observed between serum magnesium and fasting glucose, insulin, and HOMA-IR values.
Serum magnesium levels significantly differed among control, prediabetes, and diabetes groups, reinforcing its potential role in glucose metabolism.
Diabetes Mellitus (DM), which is predicted to affect 1.3 billion people worldwide in 2050, is a global health problem that requires early diagnosis and treatment due to the morbidities and high mortality rates it causes [1]. The critical goal in preventing microvascular and macrovascular complications of diabetes is to ensure blood sugar regulation. For this purpose, many clinical studies are carried out examining the pathophysiological basis of the disease.
Magnesium (Mg), one of the most common cations, has an important function in several biochemical reactions, including glucose homeostasis, phosphorylation of proteins, nucleic acid, and protein synthesis. It functions as a cofactor for a number of enzymes that participate in energy metabolism, transport of glucose throughout membranes, gluconeogenesis, insulin secretion, and connection with receptors in pancreatic cells and target tissues [2–4]. With a decrease in Mg levels, tyrosine kinase activity at the insulin receptor decreases and intracellular calcium levels increase, resulting in impaired insulin signaling. Also, Mg deficiency is linked with insulin resistance, dysfunction in pancreatic beta-cells, and hence insulin secretion [5, 6]. Patients with DM have lower amounts of intracellular free Mg2+ compared to patients without diabetes [7]. In light of all these findings, maintaining normal glucose metabolism requires the essential regulation of intra-extracellular magnesium levels [8–10].
The influence of Mg on carbohydrate metabolism pathways, particularly the impact of magnesium deficiency on glycemic control and insulin sensitivity, has been extensively investigated in clinical studies, and this interest persists. Our study aims to scrutinize the relationship between serum Mg levels and hemoglobin A1c (HbA1c) and assess their association with insulin resistance.
MATERIALS AND METHODS
Patients and Study Design
In this retrospective study, the diabetic group comprised individuals with HbA1c levels ≥6.5%, the control group consisted of individuals with HbA1c levels below 5.7%, and the prediabetes group included participants with HbA1c levels between 5.7% and 6.4%. Participants were exclusively sourced from our hospital’s internal medicine outpatient clinic who were admitted between August 2022 and August 2023 and aged from 18 to 75 years. Their demographic, anthropometric, and laboratory data were obtained from the medical records of the hospital, ensuring a comprehensive representation of the study population.
Exclusion Criteria
To maintain the study’s focus and eliminate potential confounding factors, certain exclusion criteria were applied. Participants whose laboratory data could not be accessed completely were excluded from the study. Also, the patients with chronic renal, hepatic, hematological, or oncological diseases were excluded from participation. Additionally, individuals currently using medications that could impact serum magnesium, calcium, and phosphorus levels were not included in the study. These strict inclusion and exclusion criteria aimed to enhance the study’s internal validity by ensuring a homogeneous study population with a specific focus on the association among serum Mg, HbA1c, and insulin resistance.
The determination of all participants was summarized in Figure 1.
Figure 1.
The determination of all participants.
Laboratory Analyses and Other Measurements
HbA1c values were calculated using ADAMS HV8380V, while biochemical tests were made with Roche Cobas c501. Blood pressure (BP) measurement was obtained using a manual BP cuff (Omron, Kyoto, Japan). BMI was calculated as BMI=weight (kg)/height (m2).
Primary Objective
The primary objective of this retrospective study was to assess the relationship between serum Mg and HbA1c levels. The study aimed to investigate whether variations in serum magnesium levels correlate with HbA1c levels, providing insights into the potential role of magnesium in glycemic control among diabetic individuals.
Secondary Objective
The secondary objective was to evaluate the association between serum magnesium and insulin resistance in the same cohort of individuals with type 2 DM. The study sought to explore whether there is a correlation between magnesium levels and insulin resistance, as measured by parameters such as fasting plasma glucose, insulin levels, and the homeostatic model assessment of insulin resistance (HOMA-IR). This secondary analysis aimed to contribute additional insights into the broader metabolic implications of magnesium levels in individuals with type 2 DM.
Ethics
Approval of the study was received from the Ethics Committee of Gaziosmanpasa Training and Research Hospital (decision number 147, dated 08.11.2023). Every procedure was completed in compliance with the Helsinki Declaration.
Statistical Analysis
Given the retrospective structure of this study, it is important to point out that a formal power analysis was not deemed appropriate during the study design phase. Retrospective analyses often lack the prospective planning necessary for a priori power calculations. The statistical software SPSS 26.0 version (Chicago, IL, IBM Corp.) was used for all of the analysis. The Kolmogorov-Smirnov test determined the distributions of variables. The distribution of parameters was non-parametric. Categorical parameters were indicated as percentages. We used the Kruskal-Wallis to assess significance among study groups. Also, the correlation between serum magnesium and HbA1c levels and other related laboratory parameters was determined with the Spearman test. The statistical significance cut-off value was deemed to be p<0.05.
RESULTS
The comprehensive characterization of study participants is delineated in Table 1, where a predominance of female subjects is evident, constituting 56.7% of the cohort. The median age of participants was 46 years, with an interquartile range of 33 to 56 years. Pertinent clinical attributes, encompassing body mass index, smoking status (categorized as no-smoker/current/ex-smoker), and blood pressure measurements, are detailed in Table 1 to elucidate the demographic heterogeneity within the study population.
Table 1.
Demographic and clinical characteristics of groups scale scores
| Control (n=121) | Prediabetes (n=85) | Diabetes (n=99) | p | |
|---|---|---|---|---|
| Age, years | 35 (25–46) | 48 (39–58) | 51 (44–61) | <0.001 |
| Gender | 0.019 | |||
| Female, (%) | 52.9 | 61.2 | 57.6 | |
| Male, (%) | 47.1 | 38.8 | 42.4 | |
| BMI, kg/m2 | 24.8 (22.3–29) | 30.3 (27.2–33.3) | 30.3 (27–34.3) | <0.001 |
| Smoking status, % no-smoker/current/ex | 72.7/25.6/1.7 | 67.1/29.4/3.5 | 69.7/20.2/9.1 | 0.381 |
| Hypertension | ||||
| Systolic BP, mmHg | 120 (109–131) | 126 (118–135) | 130 (120–148) | <0.001 |
| Diastolic BP, mmHg | 76 (69–82) | 80 (70–85) | 85 (80–94) | <0.001 |
BMI: Body Mass Index; BP: Blood pressure.
Table 2 unveils compelling statistical disparities in serum magnesium levels across the delineated groups, reaching a significance level of p<0.001. Concurrently, discernible differentials in fasting plasma glucose, insulin, and HOMA-IR were observed among these groups, attaining statistical significance with p-values less than 0.001 for all three parameters. It is noteworthy that while lipid parameters displayed variations, they did not attain statistical significance among the defined groups.
Table 2.
Comparison of laboratory data between the groups
| Control (n=121) | Prediabetes (n=85) | Diabetes (n=99) | p | |
|---|---|---|---|---|
| Magnesium, mg/dL | 1.96 (1.81–2.15) | 1.83 (1.53–2.03) | 1.7 (1.49–1.93) | <0.001 |
| HbA1c, % | 5.2 (5.1–5.4) | 5.8 (5.7–6) | 7,5 (6.7–8.6) | <0.001 |
| Glucose, mg/dL | 91 (87–95) | 101 (92–108) | 104 (95–123) | <0.001 |
| Insulin, mU/L | 8 (5.85–15) | 16 (10–28.1) | 15.4 (10–30.1) | <0.001 |
| HOMA-IR | 1.87 (1.34–3.17) | 3.95 (2.39–6.95) | 4.9 (2.72–8.42) | <0.001 |
| Vitamin D, μg/L | 14.2 (9.72–18.85) | 14 (8.84–19.1) | 13.5 (9.23–19.5) | 0.947 |
| Total cholesterol, mg/dL | 187 (162–212) | 208 (180–239) | 206 (180–227) | <0.001 |
| LDL, mg/dL | 111 (92–129) | 126 (105–156) | 120 (104–147) | 0.001 |
| Triglyceride, mg/dL | 90 (66–130) | 124 (93–170) | 141 (100–196) | <0.001 |
| HDL, mg/dL | 55 (45–64) | 50 (44–61) | 48 (41–56) | 0.02 |
| Creatinine, mg/dL | 0.72 (0.64–0.87) | 0.77 (0.66–0.87) | 0.75 (0.68–0.88) | 0.157 |
| Calcium, mg/dL | 9.52 (9.28–9.83) | 9.6 (9.3–9.79) | 9.53 (9.34–9.74) | 0.941 |
| Potassium, mmol/L | 4.5 (4.3–4.72) | 4.6 (4.37–4.81) | 4.53 (4.34–4.81) | 0.194 |
| Hemoglobin, g/dL | 13.6 (12.6–15.1) | 13.6 (12.2–14.75) | 13.6 (12.9–14.6) | 0.587 |
HbA1c: HemoglobinA1c; HOMA-IR: Homeostatic model assessment-insulin resistance; LDL: Low density lipoprotein; HDL: High density lipoprotein.
Concurrently, correlation analysis, as outlined in Table 3, unearthed a robust negative correlation (r =-0.316, p<0.001) between serum magnesium levels and HbA1c. Notably, a nuanced, albeit weak, negative relationship was discerned between serum magnesium and fasting plasma glucose, fasting insulin, and HOMA-IR. This nuanced exploration of correlations contributes to our understanding of the intricate interplay between serum magnesium levels and key metabolic parameters in individuals with Type 2 Diabetes Mellitus.
Table 3.
Correlation analysis between serum magnesium levels, HbA1c and other relevant parameters
| HbA1c | Glucose | Insulin | HOMA-IR | BMI | |
|---|---|---|---|---|---|
| Magnesium | |||||
| r | -0.316 | -0.167 | -0.167 | -0.198 | -0.034 |
| p | <0.001 | 0.004 | 0.003 | 0.001 | 0.554 |
HbA1c: HemoglobinA1c; HOMA-IR: Homeostatic model assessment-insulin resistance; BMI: Body mass index.
DISCUSSION
Investigating the relationship between serum magnesium and HbA1c levels and insulin resistance was the objective of our study. A significant difference was obtained among the groups in terms of Mg and HbA1c. Also, while a reverse correlation was detected between magnesium and HbA1c levels among all 3 groups, there was a weak inverse association between serum Mg and glucose, insulin and HOMA-IR.
Numerous prior studies have demonstrated a strong correlation between serum magnesium levels and glycemic control [11–13]. In a study by Galli-Tsinopoulou et al. [14] with 138 patients, an inverse correlation was found across Mg and HbA1c. Another study conducted by Kumar et al. [15] revealed that Mg deficiency is linked to a higher risk of inadequate glycemic control. In parallel with these studies, we found that patients with poor glycemic control had lower serum magnesium levels.
These results we found are supported by the findings obtained in many studies investigating the functions of magnesium in glucose homeostasis. According to Wan Nik et al.’s [16] review study from 2023 and numerous other studies, magnesium in the Mg-ATP structure regulates the glucokinase effect, and pancreatic insulin secretion decreases as a result of a reduction in glucokinase enzyme activity in magnesium deficiency. Additionally, magnesium affects insulin sensitivity, signaling, phosphorylation of receptor tyrosine kinase and many other kinases involved in glucose metabolism [2, 17].
On the other hand, numerous research demonstrate that serum magnesium replacement has no impact on glycemic control and insulin sensitivity [18, 19]. A randomized controlled study conducted by Drenthen et al. [20] in November 2023 showed that oral magnesium treatment did not provide improvement in glycemic control or insulin resistance in hypomagnesemic diabetic patients. In a prospective study with normomagnesemic diabetic patients, Navarrete-Cortes et al. [21] found no significant change in HbA1c, fasting glucose, insulin, or HOMA-IR values after magnesium treatment. Although the effect of magnesium treatment was not evaluated because of our study’s retrospective design, in parallel with the above-mentioned studies, a strong correlation was not detected between insulin sensitivity and magnesium levels.
Conclusion
In conclusion, our study adds valuable insights to the current understanding of the interplay between serum magnesium levels and glycemic control. Yet, the conflicting nature of existing literature highlights the intricacies of this relationship, emphasizing the imperative for larger, well-designed prospective studies to provide a more nuanced comprehension of magnesium’s role in metabolic regulation among individuals with Type 2 DM.
Footnotes
Cite this article as: Erinc O, Yesilyurt S. Relationship between serum magnesium levels and glycemic control and insulin resistance. North Clin Istanb 2025;12(2):239–243.
Ethics Committee Approval
The Gaziosmanpasa Training and Research Hospital Clinical Research Ethics Committee granted approval for this study (date: 08.11.2023, number: 147).
Authorship Contributions
Concept – OE; Design – OE; Supervision – OE, SY; Fundings – OE; Materials – OE, SY; Data collection and/or processing – OE, SY; Analysis and/or interpretation – OE; Literature review – OE; Writing – OE; Critical review – OE, SY.
Conflict of Interest
No conflict of interest was declared by the authors.
Use of AI for Writing Assistance
The authors declared that artificial intelligence supported technologies were not used in our study.
Financial Disclosure
The authors declared that this study has received no financial support.
Peer-review
Externally peer-reviewed.
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