Magnesium Status in Patients with Type 2 Diabetes (about 170 cases)

Abstract

Magnesium (Mg) is an extremely important mineral. It plays major roles in physiological activities of the body. Lower intake of Mg and low-serum Mg concentrations are associated with metabolic syndrome, insulin resistance, and Type-2 diabetes. Aim: The aim of the study is to evaluate the association between concentration levels of serum Mg and common complications and co morbidities of diabetes mellitus and other biochemical indices. It is a case control study conducted in our department of endocrinology in Hassan II University Hospital of Fez from January 2015 to 2018. Our patients were classified into two groups. Low Mg (Group 1, n = 85) and normal Mg group (Group 2, n = 85). We evaluated demographics characteristics of our patients; the association between Mg status and clinical, biological parameters; and association between Mg status and degenerative complications. Our study included 170 patients. The research results showed that serum Mg level was strongly related to age, sex, diabetes duration, body mass index, hypertension, and glycosylated hemoglobin. Concerning common complication; we only found a negative correlation between Mg level and the existence of nephropathy. We did not find significant correlation with retinopathy; neuropathy; and macroangiopathy. The study has demonstrated that a low Mg level is correlated with a poor control glycemic; high blood pressure and nephropathy in patients with Type 2 diabetes. However, more research is needed to confirm these effects.

INTRODUCTION

Diabetes is a major public health problem that has attained epidemic proportions globally. According to international diabetes federation, there are 425 million people with diabetes in the world. There will be 629 million people with diabetes in the world in 2045.[1] Type 2 diabetes millitus is the most common form of diabetes mellitus (DM). Therefore, it is urgent to develop an effective preventive strategy to control this epidemic. Currently, it is well proven that diet may play important roles in increasing the risk of developing diabetes.[2] Magnesium (Mg) is an extremely important mineral which is found naturally in many foods. It plays major roles in physiological activities of the body including normal nerve and muscle function, cardiac excitability, and insulin metabolism.[3] Furthermore, Mg is an important ion in all living cells being a cofactor of many enzymes involved in glucose metabolism.[4] These enzymes are activated by the MgATP2+ complex which is the essential substrate for their functioning.[5] Lower intake of Mg and low serum Mg concentrations are associated with metabolic syndrome, insulin resistance, and Type-2 diabetes.[6] Several studies have shown that Mg intake in diabetic patients is often below recommended levels.[7] The recommended dietary reference intake is about 301–420 mg/day.[8] The normal serum Mg is about 1.9–2.5 mg/dl. Patients are considered frankly hypomagnesemic with serum Mg concentrations ≤0.61 mmol/L or 1.5 mg/dL.[9] Mg concentrations ≤0.75 mmol/L or 1.8 mg/dL may be considered as preclinical hypomagnesemia.[10] Our study seeks the association between concentration levels of serum Mg and common complications and comorbidities of DM and other biochemical indexes.

MATERIALS AND METHODS

Study design and patients

This is a case–control study conducted Department of Endocrinology, Diabetology, and Nutrition at University Hospital Center Hassan II in Fez. Patients with Type 2 diabetes admitted in our department between January 2015 and December 2018 were included in this study. We distinguished two groups. G1: Patients Type 2 diabetics with a normal Mg and G2: Patients Type 2 diabetic with hypomagnesemia. These two groups are matched for age and sex.

We excluded from our study: Records without making a full set of biochemical examination, patients with Type 1 diabetes, pregnant and lactating women, those taking diuretics or Mg supplementation or having persistent diarrhea, vomiting, and patients with renal failure.

Basic data were obtained (pathological history, height, weight, body mass index (BMI), waist circumference, and blood pressures), biological evaluation (glycosylated hemoglobin [HbA1c] and the fasting blood glucose were obtained; lipid profile, blood urea, serum creatinine, and 24 h urinary albumin were estimated). Serum Mg was measured by colorimetry and a value of Serum Mg <1.8 mg/dl was considered to be hypomagnesemia. The common complications (diabetic retinopathy, diabetic nephropathy, diabetic neuropathy, and diabetic macroangiopathy…) were obtained from databases also.

Statical analysis

Statistical analysis was performed using Microsoft Excel 2004 (XML) and d'Epi Info 7 (7.2.2.6 février 2018), Centers for Disease Control and Prevention at United states. The collected information was summarized using the descriptive statistics such as frequency and percentage of qualitative data, mean and standard deviation for quantitative data. Statistical result was considered statistically significant at P < 0.05.

RESULTS

There were 170 patients evaluated and enrolled. According to the serum level of Mg, patients were classified into two groups: low Mg (Group 1, n = 85) and normal Mg group (Group 2, n = 85).

Demographics characteristics of our patients are shown in Table 1. Fifty six (33%) were male and One hundred fourteen with a sex-ratio H/F: 0, 49. The mean age of the patients was 61.42 ± 10.89 years (range 29–84 years). The average duration of diabetes was 12.62 ± 8.20 years. Our patients had a higher BMI with an average of 30.15 ± 7.10 kg/m². The mean serum Mg of all the diabetic patients was 19.06 ± 1.31.

Table 1.

Demographics characteristics

Characteristics	T2D + normal magnesium	T2D + hypomagnesemia	Total	P
Number of subjects	85	85	170
Age (years)	61.51±10.36	61.34±11.46	61.42±10.8	0.0009
Sex (H/F)	36/49	20/65	56/114	0.029
Duration of diabetes (years)	12.77±8.67	12.47±7.73	12.62±8.20	0.021
Treatment
Oral hypoglycemic	24	38	62
Insulin	24	17	41
Oral hypoglycemic + insulin	35	25	60
Diet	2	5	7
BMI (kg/m2)	29.72±7.54	30.58±6.66	30.15±7.10	0.032
Waist circumference (cm)	101.24±22.21	102.87±19.75	102.05±20.98	0.019
Arterial hypertension (n)	51	54	105	0.019
HbA1c (%)	9.61±1.74	10.82±2.11	10.21±1.92	0.005
Serum magnesium (mg/l)	21.32±2.61	16.81±1.33	19.06±1.31
Serum calcium (mg/l)	92.80±15.51	93.76±12.5	93.28±14.14
Urea (g/l)	0.42±0.35	0.34±0.25	0.38±0.30
Creatinine (mg/l)	10.85±11.67	9.73±7.97	10.29±9.98
Dyslipidemia
Hypo HDL	1.37±0.34	1.24±0.31		0.088
Hyper TG	2.42±1.16	2.33±1.03		0.074
Hyper LDL	0.34±0.09	0.37±0.18		0.065

BMI=Boby mass index, HbA1c=Glycosylated hemoglobin

Association between magnesium status and clinical, biological parameters

Comparing two groups, there was a statistical difference in the sex (P = 0.029), ages (P = 0.009) and diabetes duration (P = 0.021). However; the BMI was higher in patients with hypo Mg. Moreover, among the group with hypomagnesaemia; there was more hypertension in comparison with normal Mg group (P = 0.019). The serum Mg in the hypomagnesemia group was 16.81 ± 1.33 mg/l while the normal Mg group was 21.32 ± 2.61 mg/l.

In addition, patients with normal Mg had better glycemic control (9.61% ± 1.74% vs. 10.82% ± 2.11%, P = 0.005). Concerning dyslipidemia, there was no difference between groups.

Association between magnesium status and degenerative complications

There was no difference between the groups for retinopathy and neuropathy (P = 0.30 for retinopathy, P = 0.11 for neuropathy). However, nephropathy was more common in group with hypomagnesemia (P = 0.026) [Table 2].

Table 2.

Diabetic microangiopathy

Degenerative complications	Number of patients	Hypomagnesemia (%)	Normomagnesemia (%)	P
Retinopathy	61	41	30	0.30
Nephropathy	48	34	22	0.026
Neuropathy	19	9.41	12.9	0.11

There was no difference between the groups concerning macroangiopathy (P = 0.065 for ischemic cardiomyopathy, P = 0.14 for arteriopathy, P = 0.11 for diabetic foot) [Table 3].

Table 3.

Diabetic macroangiopathy

Degenerative complications	Number of patients	Hypomagnesemia (%)	Normomagnesemia (%)	P
Ischemic cardiomyopathy	46	28.23	25.88	0.065
Arteriopathy	11	6	7	0.14
Diabetic ulcer	8	4.7	4.7	0.11

DISCUSSION

Mg is an intracellular ion with an essential role in several biological reactions.[4] Indeed, he has a fundamental role in different biochemical processes such as maintenance of the pancreatic beta cell cycle, release of insulin, regulation of insulin action, insulin-mediated glucose uptake, activation of glucose metabolizing enzymes, maintenance of vascular tone, and DNA synthesis.[11] In previous studies, Mg deficiency has been reported in patient with Type 2 diabetes. However, some workers have also reported normal and even high levels.[12] In addition, a low serum Mg level has been shown to induce new diabetes. Besides, it effects on the existing diabetes and its co morbid conditions.[13] The mechanism of Mg deficiency in diabetes is not clearly elucidate but it seems that the most important causes are the reduction of Mg intake and/or augmentation of Mg urinary loss while Mg absorption and retention seem to be maintained.[14]

Association between magnesium status and clinical, biological parameters

It seems therefore that plasma Mg concentration is an insensitive, but highly specific indicator of low Mg status.[14] That is why the serum or plasma Mg measurement is the most readily available and widely used test of Mg status. In our study, we assessed the serum Mg. The results of our study showed that serum Mg level was strongly related to age, sex, diabetes duration, BMI, and hypertension. It was similarly in the study of Guerrero-Romero et al., who noted that age, alcohol consumption and use of diuretics were risk factors for low-serum Mg levels in diabetic patients.[15] Mg depletion may cause an insulin-resistant state, poor glycemic control, and disordered lipid metabolism.[16] Mahalle et al. have found that diabetes, dyslipidemia, and hypertension were inversely related with serum Mg levels.[17] Besides, Solati et al. found that Mg supplementation could significantly decrease both systolic and diastolic blood pressure.[18] It can be explained by the fact that Mg deficiency increases the intracellular Ca/Mg ratio, vascular smooth muscle tone and smooth muscle cell response to external constrictor stimuli increases, which leads to vasoconstriction and as a result elevation of blood pressure.[18] In our study, we noted a statistically significant difference between HbA1c level; existence of hypertension but we did not observe a difference concerning dyslipidemia.

Association between magnesium status and degenerative complications

Previous studies have revealed that lower Mg level may lead to the occurrence and development of diabetic microvascular and macroangiopathy complications.[19] Additionally to poor glycemic control, Dasgupta et al. noted that hypomagnesemia is associated with retinopathy, nephropathy, and foot ulcers.[19] In his cohort, Arpaci et al., observe that nephropathy was common in the hypomagnesemic group compared to the normomagnesemic group regardless of age and duration of diabetes.[20] Moreover, Coronary Artery Risk Development in young Adults Study showed an inverse relationship between Mg intake and the incidence of diabetes.[21] Similarly, we only found a negative correlation between Mg level and the existence of the nephropathy. However, it is worth to note that our patients with hypomagnesemia and nephropathy had higher BMI and blood pressure. Those two parameters can explain also the increase of nephropathy in our study. In disagreement with this report, we did not note a difference in the presence of retinopathy and macropathy complications. Others studies argued that in diabetics with microalbuminuria, serum Mg might be reduced due to lower serum albumin concentration.[14] Taking into an account, the increasing prevalence of diabetes and its complications, scientists are trying hard to discover new prevention and treatment methods for diabetes.[22] It appears that Mg supplementation had proven to be effective in improving insulin sensitivity and glucose.[18] On the other hand, researchers think that, one of the principal sites of Mg action can be the muscles. It is possible that Mg can help translocation of glucose transporter number 4 to the cell membrane, to take place.[18] Furthermore, a meta-analysis of 34 trials involving 2028 participants; published by Zhang et al., reported that 368 mg of supplemental Mg daily for 3 months will lower systolic BP by 2 mmHg and diastolic BP by 1.78 mmHg.[23] However, more research is needed to confirm these effects.

The limitations of this study are the relatively small sample size and measurement of serum Mg instead erythrocyte intracellular Mg (As Mg is a predominantly intracellular ion, its serum measurements are not representative of Mg status or intracellular pool). There are still many aspects need further study and exploration.

CONCLUSION

In summary, our study has demonstrated that a low Mg level is correlated to a poor control glycemic; high blood pressure and nephropathy in patients with Type 2 diabetes. Indeed, large-scale clinical trials are needed to determine whether the correction of Mg deficiency could be effective to reduce the incidence and to further elucidate the association between serum Mg and nephropathy. However, we did not find any significant association between retinopathy, neuropathy, macroangioapthy, and low Mg status. It may be prudent in clinical practice to periodically monitor plasma Mg concentrations in diabetic patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.