|Year : 2021 | Volume
| Issue : 4 | Page : 442-446
Correlation of plasma magnesium with insulin resistance in type 2 diabetes: A cross-sectional study from South-western Nigeria
Jokotade Adeleye1, Arinola Esan2, Taoreed Adegoke Azeez2, Oyebola Oluwagbemiga Sonuga3
1 Endocrinology Unit, Department of Medicine, College of Medicine, University of Ibadan, Ibadan, Nigeria
2 Endocrinology Unit, Department of Medicine, University College Hospital, Ibadan, Nigeria
3 Department of Chemical Pathology, University College Hospital, Ibadan, Nigeria
|Date of Submission||04-Mar-2021|
|Date of Decision||11-May-2021|
|Date of Acceptance||21-May-2021|
|Date of Web Publication||12-Jan-2022|
Dr. Taoreed Adegoke Azeez
Endocrinology Unit, Department of Medicine, University College Hospital, Ibadan.
Source of Support: None, Conflict of Interest: None
Introduction: Insulin resistance (IR) is a core component of the pathophysiology of type 2 diabetes mellitus (DM). Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) is the most commonly used marker of IR. Plasma magnesium is a relatively cheap analyte and has been linked with the pathophysiology of IR. This study primarily was aimed at evaluating the possible use of plasma magnesium as a surrogate marker of IR in type 2 diabetes. Materials and Methods: The study was a hospital-based cross-sectional study carried out at a tertiary hospital in South-western Nigeria between March and September 2018. The study was conducted on 70 persons with diabetes, and age- and sex-matched 70 controls who met the eligibility criteria were recruited into the study. Ethical approval was obtained and informed consent was obtained from the participants. Fasting plasma glucose, fasting plasma insulin, and plasma magnesium were measured using standard protocols. HOMA-IR was determined using the appropriate formula. Data analysis was carried out using the Statistical Package for Social Sciences software, (SPSS) version 22. Results: The mean age of the participants was 53.34 ± 9.57 years and that of the gender-matched controls was similar. Frequency of hypomagnesemia was significantly higher in the participants compared with controls (25.7% vs. 5.7%; P < 0.001). Similarly, a significantly greater proportion of the study participants (62.9%) had IR as expected compared with just 8.7% of the controls. The mean plasma magnesium (mg/dL) among the participants was significantly lower than that of the controls (1.73 ± 0.16 vs. 1.87 ± 0.14; P < 0.001). As expected, the mean HOMA-IR in the participants was significantly higher than that of the controls (2.64 ± 0.91 vs. 1.71 ± 0.32; P<0.001). There was a statistically significant negative correlation between plasma magnesium and IR among the participants (r=−0.443; P<0.001). However, among the controls, there was no statistically significant correlation between plasma magnesium and HOMA-IR (r=−0.034; P = 0.778). Conclusion: Plasma magnesium was found to correlate significantly with IR and may be used as a surrogate marker of IR in persons with type 2 DM but not in the general population.
Keywords: Insulin resistance, plasma magnesium, South-Western Nigeria, type 2 diabetes mellitus
|How to cite this article:|
Adeleye J, Esan A, Azeez TA, Sonuga OO. Correlation of plasma magnesium with insulin resistance in type 2 diabetes: A cross-sectional study from South-western Nigeria. J Diabetol 2021;12:442-6
|How to cite this URL:|
Adeleye J, Esan A, Azeez TA, Sonuga OO. Correlation of plasma magnesium with insulin resistance in type 2 diabetes: A cross-sectional study from South-western Nigeria. J Diabetol [serial online] 2021 [cited 2022 Jan 27];12:442-6. Available from: https://www.journalofdiabetology.org/text.asp?2021/12/4/442/335584
| Introduction|| |
Diabetes mellitus (DM) is a heterogeneous group of metabolic disorders characterized by chronic hyperglycemia due to a defect in insulin secretion, action, or both. There are various types but type 2 DM is the commonest type. The incidence is rising despite increased awareness and better diagnostic tools and wider treatment options. This has been a stimulus for researchers to gain better understanding of the pathophysiology of type 2 DM.
Insulin resistance (IR) is central to the pathophysiology of type 2 DM and is defined as the attenuated response of tissues to a given amount of insulin, either endogenous or exogenous. Despite IR being an integral mechanism in the development of type 2 DM, it cannot yet be directly measured clinically. The hyperinsulinemic euglycemic clamp is the gold standard method of quantifying IR but it is laborious, time-consuming, and expensive.
Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) is a simple and reliable method for determining IR. It is the most commonly used IR index but it has its own drawbacks too. Insulin secretion is pulsatile, so measuring a spot fasting insulin concentration may not be ideal as a marker due to the high intrapersonal variability. Wallace et al. have also argued that HOMA-IR is not comparable across ethnic groups. This has led to research efforts aimed at identifying a surrogate marker that is comparable across ethnic groups. It is also technically difficult to evaluate HOMA-IR in patients on insulin therapy due to the interference of assays. All these inadequacies have led to researches in identifying potential surrogate markers of IR.
Magnesium is an essential mineral needed for various metabolic processes in the cells. Magnesium is required for post-receptor signaling when insulin binds to its receptor; therefore, it has been proposed that hypomagnesemia would be associated with IR. Insulin receptor, a member of the tyrosine kinase receptor family, is a glycoprotein with two alpha chains and two beta chains. Activation of the receptor by insulin leads to auto-phosphorylation of the receptor and phosphorylation of other proteins in the insulin action cellular cascade. Magnesium is an essential cofactor in all phosphorylation reactions, and magnesium deficiency is believed to impair this pathway causing IR. Similarly, hyperinsulinemia, which is a common finding in insulin-resistant state, alters renal tubular handling of magnesium, thereby explaining the link between plasma magnesium and IR.
The aim of this study was to evaluate the correlation between plasma magnesium and IR among patients with type 2 DM.
| Materials and Methods|| |
The study was a hospital-based cross-sectional study carried out at the University College Hospital (a tertiary hospital in South-western Nigeria) from March 1, 2019 to June 30, 2019. The sample size formula for a cross-sectional study, as documented by Charan and Biswas, was adopted in this study and the calculation is shown below:
n is the minimum sample size in each group;
Z(1−α) is the standard normal variate at P < 0.05 = 1.96;
SD is the standard deviation of a previous study done in Nigeria on the level of serum magnesium abnormalities among patients with type 2 DM, which is 0.2;
d is the precision or absolute error which was taken as 0.05.
Thus, the minimum sample size in each group (n) can be calculated as follows:
Assuming a non-response rate of 10%
n = 61 + 6 = 67.
Therefore, a total number of 140 individuals were recruited into the study: 70 adult patients with type 2 DM were regarded as the study participants and 70 apparently healthy age- and gender-matched adults without type 2 DM served as the controls. The controls were members of the community who fulfilled the eligibility criteria for controls. Ethical approval for this study was obtained from the joint University College Hospital and University of Ibadan Ethical Review Committee. Written informed consent was obtained from the participants.
Adult males and females above 30 years who had been diagnosed to have type 2 DM according to the WHO criteria were recruited into the study. However, individuals with type 2 DM who also had an acute illness or metabolic decompensation, diagnosed hypomagnesemia or hypermagnesemia, or who were pregnant were excluded from the study. Other exclusion criteria were chronic diarrhea, ingestion of magnesium-containing medications, recent hospital admission (within 3 months), or those on insulin therapy. The eligibility criteria for the controls were similar to those of the main participants but DM was excluded in them using the standard criteria.
Metformin was the most commonly used oral glucose-lowering agent and was being taken by approximately 90% of the study subjects. Almost half of the subjects studied were using sulfonylureas. Dipeptidyl peptidase IV (DPP-IV) inhibitors were being used by 12.9% of the subjects, whereas 4.3% were on pioglitazone.
Fasting plasma glucose was determined by glucose oxidase method on automated chemistry analyzer LandWind C 100 plus. The intra-assay and inter-assay coefficients of variations were 2.98% and 3.02%, respectively. Fasting plasma insulin was measured by enzyme-linked immunosorbent assay using a Cell Biolab Human Insulin ELISA kit. The intra-assay and inter-assay coefficients of variations were 4.83% and 5.74%, respectively. IR was determined using the HOMA method as shown below:
Plasma magnesium was determined using Xylidly Blue Monoreagent method on automated chemistry analyzer LandWind C 100 plus. Coefficient of variation was 1.84%. The outputs were satisfactory. Data analysis was carried out using the Statistical Package for Social Sciences software (SPSS), version 22.
Quantitative variables were presented as mean ± standard deviation or median (where deemed appropriate). Categorical variables were presented as frequencies or proportions. Data were presented with frequency tables, bar charts, and scatterplots as appropriate. Quantitative clinical and laboratory variables of the participants with hypomagnesemia were compared with the participants without hypomagnesemia using Student’s t-test. Categorical clinical and laboratory variables of the participants with hypomagnesemia were compared with those of the participants without hypomagnesemia using χ2 and Fisher’s exact tests. Association between quantitative variables was determined using Pearson’s correlation. A P-value less than 0.05 was considered to be statistically significant.
Definition of terms
Hypomagnesemia is plasma magnesium less than 1.7 mg/dL, and insulin resistance is HOMA-IR greater than 2.
| Results|| |
[Table 1] shows the sociodemographic characteristics of the participants. The mean age (years) of the participants was similar to that of controls (53.34 ± 9.57 vs. 53.01±10.01; P = 0.843). [Table 2] depicts the medical history of the participants. Among the study participants with type 2 DM, the mean duration of diabetes was 6.29 ± 2.78 years. As shown in [Table 2], the proportion of persons with systemic hypertension was significantly higher among the participants with type 2 DM when compared with the controls (P < 0.01). [Table 3] compares the biochemical parameters of the patients with the controls.
|Table 1: Sociodemographic characteristics of the participants and the controls|
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The average plasma magnesium (mg/dL) among the participants was significantly lower than that of the controls (1.73 ± 0.16 vs. 1.87 ± 0.14; P < 0.001). Hypomagnesemia was found in 18 individuals (25.7%) among the study participants when compared with 4 (5.7%) among the controls, and this difference in the proportion of hypomagnesemia was statistically significant (P < 0.001).
Similarly, a significantly greater proportion of the study participants (62.9%) had IR compared with just 8.7% of the controls. This difference in the frequency of IR between the participants and the controls was also statistically significant (P < 0.001). The mean HOMA-IR in the participants was significantly higher than that of the controls (2.64 ± 0.91 vs. 1.71 ± 0.32; P<0.001).
[Figure 1] is a scatter plot showing the inverse relationship between HOMA-IR and plasma magnesium. There is a statistically significant negative correlation between plasma magnesium and IR among the participants (r= −0.443; P < 0.001). However, among the controls, there was no statistically significant correlation between plasma magnesium and HOMA-IR (r= −0.034; P = 0.778).
|Figure 1: Scatter plot showing the relationship between plasma magnesium and HOMA-IR among patients with type 2 DM|
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| Discussion|| |
This study was conducted among patients with type 2 DM as well as apparently healthy age and gender-matched controls who had met the earlier stated eligibility criteria. The frequency of hypomagnesemia among type 2 DM participants in this study was significantly higher than that of the controls (25.7% vs. 5.7%; P < 0.001). This is in keeping with the findings of other authors who have reported similar frequency of hypomagnesemia among persons with type 2 DM.,,
Ozcaliskan et al. reported that the frequency of hypomagnesemia among a Turkish cohort of type 2 DM patients was 18.5%. In a study done in Nigeria, Ajibola et al. reported a frequency of hypomagnesemia among type 2 DM patients as 18.2%, which was slightly lower than what was found in this study. In a similar study conducted in India, Saproo and Singh documented 30% as the frequency of hypomagnesemia in their type 2 DM participants. These studies all demonstrated a significantly higher frequency of hypomagnesemia among individuals with type 2 DM when compared with controls. Possible explanations for this observation include reduced dietary intake (due to dietary restriction and diabetic gastroparesis), impaired absorption (due to diabetic diarrhea and binding with drugs such as metformin), and enhanced magnesiuria (due to glomerular hyperfiltration, osmotic diuresis, and proteinuria).
This study showed that plasma magnesium had significant negative correlation with HOMA-IR. This implies that the lower the plasma magnesium was, the higher the magnitude of IR among patients with type 2 DM. Conversely, among the controls, the association between plasma magnesium and HOMA-IR did not attain statistical significance. This therefore suggests that plasma magnesium can serve as a marker of IR only in persons with type 2 DM but not in the general population. Several authors, working in different parts of the world, have also reported a statistically significant negative correlation between plasma magnesium and IR.,,, The dependence of proteins involved in insulin signaling on magnesium has been proposed as a plausible explanation for the association between plasma magnesium and IR.
| Conclusion|| |
Hypomagnesemia is frequent in type 2 DM and could be a cheap and easily measurable surrogate marker of IR in persons living with type 2 DM.
The study was hospital-based so generalizability to the community calls for caution. Also, it was a cross-sectional study and therefore would not be able to establish causality.
Ethical approval and patients’ consent
Consent for publication
The authors hereby give the journal the consent to publish the article.
Availability of supporting data
Jokotade Adeleye contributed in the study conception, study design, and reviewing and editing of the manuscript. Arinola Esan contributed in the study design, reviewing, and editing of the manuscript. Taoreed Adegoke Azeez contributed in the study conception, study design, data collection, writing, reviewing, and editing of the manuscript. Oyebola Oluwagbemiga Sonuga contributed in the study design, data collection, sample analyses, and editing of the manuscript.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3]