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Коморбідний ендокринологічний пацієнт
Коморбідний ендокринологічний пацієнт

Международный эндокринологический журнал Том 18, №2, 2022

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Дефіцит магнію при цукровому діабеті 2-го типу та його вплив на глікемічний контроль та ускладнення цукрового діабету

Дефіцит магнію при цукровому діабеті 2-го типу та його вплив на глікемічний контроль та ускладнення цукрового діабету

Авторы: Savas Karatas, Yalcın Hacıoglu, Şennur Kose
Istanbul Research and Education Hospital, Fatih, Istanbul, Turkey

Рубрики: Эндокринология

Разделы: Клинические исследования

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Резюме

Актуальність. У світі спостерігається ріст захворюваності на цукровий діабет (ЦД). Магній належить до важливих елементів організму й виконує безліч життєво важливих функцій. Зараз відзначається тенденція досліджувати вплив магнію на патогенез ЦД 2-го типу та його ускладнення. У той же час потрібно більше доказів, щоб встановити взаємозв’язок між вмістом магнію та ЦД 2-го типу. Тому мета дослідження полягала у встановленні частоти дефіциту магнію в турецьких пацієнтів із ЦД 2-го типу та його впливу на глікемічний контроль та ускладнення ЦД. Матеріали та методи. У дослідження були залучені 296 пацієнтів із ЦД 2-го типу та 96 здорових осіб групи контролю віком 18–65 років. Після критеріїв виключення пацієнтів із ЦД 2-го типу розділили на дві групи за показником вмісту магнію, провели порівняння метаболічних характеристик пацієнтів обох груп. Також порівнювали частоту артеріальної гіпертензії, складових метаболічного синдрому, ішемічної хвороби серця та мікроальбумінурії залежно від наявності дефіциту магнію. Результати. Дефіцит магнію виявлений у 35,5 % (86/242) пацієнтів із ЦД 2-го типу, у 4,1 % (4/96) — у контрольній групі. Дефіцит магнію був більш вираженим у пацієнтів жіночої статі (64/86, 74,4 %). У чоловіків спостерігалася більша частота нормального рівня магнію — 89/166 (53,6 %) (p < 0,01). Пацієнти з ЦД 2-го типу зі зниженим вмістом магнію в крові вірогідно не відрізнялися за показником глікованого гемоглобіну HbA1c (9,0 ± 1,9 % проти 8,8 ± 1,6 %, p = 0,35) та рівнями глюкози в крові натще (197,24 ± 87,25 мг/дл проти 177,85 ± 57,22 мг/дл, p = 0,35). Пацієнти з ЦД 2-го типу зі зниженим вмістом магнію в крові мали вірогідно вищі рівні гіперліпідемії (48,8 % (42/86) проти 41,0 % (64/156), p = 0,04). Частота метаболічного синдрому (89,0 % (73/82) проти 83,1 % (123/148), p = 0,22) та ішемічної хвороби серця (39,5 % (34/86) проти 35,9 % (56/156), p = 0,85) не відрізнялася між групами обстежених. Частота артеріальної гіпертензії (81,4 % (70/86) проти 67,9 (60/156), p = 0,04) і мікроальбумінурії (66,7 % (38/57) проти 43,7 (58/119), p = 0,03) була вірогідно вищою в групі хворих на ЦД 2-го типу з низьким умістом магнію в крові. Висновки. Дефіцит магнію доволі часто спостерігається у хворих на ЦД 2-го типу, однак цей дефіцит вірогідно не впливає на глікемічний контроль. З іншого боку, встановлено, що частота артеріальної гіпертензії, мікроальбумінурії та гіперліпідемії зростає у хворих на ЦД 2-го типу з дефіцитом магнію.

Background. Diabetes has become more often in all over the world, magnesium is an essential element of the body and has lots of vital functions. There has been a trend to investigate magnesium’s effect on type 2 diabetes pathogenesis and its complications. Still, more data is needed to reveal magnesium and T2 diabetes mellitus (DM) association, therefore we aimed to investigate how common magnesium deficiency in Turkish T2DM patients, and its effect on diabetes control and diabetes complications. Materials and methods. 296 patients with type 2 DM and 96 healthy controls aged between 18–65 years were enrolled in the study. After exclusion criteria, T2DM patients were divided into 2 groups according to magnesium deficiency, metabolic and physical properties of the groups were compared. Also, hypertension, metabolic syndrome, coronary artery disease, and microalbuminuria were also compared according to magnesium deficiency. Results. Magnesium deficiency was found 35.5 % (86/242) in patients with type 2 DM, 4.1 % (4/96) in the control group. Magnesium deficiency was more in female patients (64/86, 74.4 %), male patients had more normal magnesium levels 89/166, 53.6 %) (p < 0.01). Hypomagnеsemia patients with T2 DM didn’t show difference in HbA1c (9.0 ± 1.9 % vs 8.8 ± 1.6 %, p = 0.35), and fasting blood glucose levels (197.24 ± 87.25 vs 177.85 ± 57.22 mg/dl, p = 0.14). Hypomagnеsemia patients with T2DM had significantly higher hyperlipidemia levels (48.8 % (42/86) vs 41.0 % (64/156), p = 0.04). Metabolic syndrome (89.0 % (73/82) vs 83.1 % (123/148), p = 0.22) and coronary artery syndrome (39.5 % (34/86) vs 35.9 % (56/156), p = 0.85) didn’t differ between groups. Hypertension (81.4 % (70/86) vs 67.9 (60/156), p = 0.04) and microalbuminuria (66.7 % (38/57) vs 43.7 (58/119), p = 0.03) were significantly higher in the hypomagnеsemia T2DM group. Conclusions. Magnesium deficiency is not rare in T2DM, however, this deficiency didn’t impact blood glucose control at a significant level in current study, on the other hand, hypertension, microalbuminuria, and hyperlipidemia components of diabetes have been shown to increase with magnesium deficiency.


Ключевые слова

цукровий діабет 2-го типу; магній; мікроальбумінурія

type 2 diabetes mellitus; magnesium; microalbuminuria

doi: http://dx.doi.org/10.22141/2224-0721.18.2.2022.1155

Introduction

Type 2 diabetes mellitus (T2DM) continues to become more frequent in Turkey and all over the world. Always growing number of  studies concentrate on T2DM treatment options, and also focuses on the pathophysiology of T2DM and its complications. Magnesium is an abundant element in the body and has an important responsibility in heart, nerve and skeletal muscle function, and gene expression [1]. Furthermore, magnesium deficiency has been linked with cardiovascular diseases, colorectal cancer and stroke [2–4]. 
Magnesium levels lower than 1.8 mg/dl (0.75 mmol/l) was defined as subclinical hypomagnesemia and lower than 1.5 mg/dl (0.65 mg/dl) was defined as frankly hypomagnesemia [1].
Recently several studies have suggested magnesium deficiency has been found correlated with insulin resistance [5–7]. In addition, another study found, magnesium supplementation decrease insulin resistance in T2DM patients [8]. Since insulin resistance is an important component in T2DM and even progression of its complications, we should consider magnesium deficiency in mechanisms and treatment perspectives.
There has been still shortage of data about magnesium deficiency and diabetes. Therefore, in this study, we purposed to research magnesium deficiency in patients with T2DM and investigate whether magnesium deficiency has a role in blood glucose control, lipid abnormalities in diabetes.

Materials and methods

296 patients with type 2 DM, aged between 18–65 years were enrolled in the study. All patients were routinely followed up by Endocrinology and Metabolism department between April 2019 and December 2021. Age smaller than 18 years, pregnancy, liver disease, active infection, use of any medications (including diuretics, magnesium supplement medications, SGLT-2 inhibitors, antibiotics, antifungals etc.), or any illness (including chronic diarrhea, renal failure) that affects magnesium levels were exclusion criteria. After exclusion criteria, 244 patients with type 2 DM were eligible for the study. 96 healthy controls were included as a comparison group. Weight (kg) and height (m) were measured using standard methods. The waist circumference (WC) was measured at the midpoint between the underside of the chest and the uppermost edge of the iliac crest in the standing position.
All the laboratory analyses were studied in the same laboratory. Serum creatinine (Cre) was measured by enzyme-linked immunosorbent assay (ELISA) and glomerular filtration rate (GFR) was measured by CKD-EPI method (ml/min/1,75 m2). Patients were divided into type 1 and type 2 according to previous records. Serum magnesium was measured by colorimetry. Magnesium level lower than < 1.8 mg/dl was defined as subclinical hypomagnesemia and lower than 1.5 mg/dl was defined as frank hypomagnesemia. Hyperlipidemia was defined as the use of cholesterol-lowering medications or LDL > 100 mg/dl.
Ethical approvation was taken from Istanbul Research and Educational Hospital (01/22/16)
Statistics. Statistical evaluations were performed using IBM SPSS 22.0 (Statistical Package for the Social Sciences software version 22.0). Descriptive analyses were expressed as median (min-max) or mean ± standard deviation (SD) and percentages (%), Shapiro-Wilk test was used for normality. The Chi-square test or Fisher’s exact test, where appropriate, was used for categorical variables. Student’s t-test was used for comparison of normality distributed continuous variables of two groups. The Mann-Whitney U-test was used for comparisons of continuous variables that were not normally distributed between two groups. Logarithmic transformation was used to continuous variables that were not normally distributed.

Results 

Magnesium deficiency was found 35.5 % (86/242) in patients with type 2 diabetes, 4.1 % (4/96) in the control group. The mean age of T2DM patients according to magnesium deficiency was not different between groups. Diabetes duration in magnesium-deficient T2DM patients (13.87 ± 8.20 years) was longer than magnesium normal patients with T2DM (11.23 ± 7.02 years) (p = 0.01). Magnesium deficiency was more prominent in female patients (64/86, 74.4 %), male patients had more normal magnesium levels 89/166, 53.6 %) (p < 0.01) (Table 1).
Hypomagnеsemia patients with T2DM didn’t show difference in HbA1c (9.0 ± 1.9 % vs 8.8 ± 1.6 %, p = 0.35), and fasting blood glucose levels (197.24 ± 87.25 vs 177.85 ± 57.22 mg/dl, p = 0.14). Serum LDL cholestrole (128.59 ± 49.3 vs 120.40 ± 41.33 mg/dl, p = 0.49) and tryglyceride (214.25 ± 177.20 vs 201.13 ± 150.21 mg/dl, p = 0.56) levels were at non-significantly higher levels in hypomagnеsemic patients with T2DM. HDL-c levels (48.31 ± 12.14 vs 50.43 ± 44.46 mg/dl, p = 0.66) were non-significantly lower in hypomagnеsemic T2DM patients (Table 2).

Discussion

Hypomagnesemia was found to be higher in T2DM patients (35.5 %). This was consistent with other study results ranging from 11  to 44 % [9–11]. Glucose and lipid levels were statistically insignificantly higher in patients with T2DM. Hyperlipidemia, hypertension, and microalbuminuria were found significantly higher in patients with T2DM.
Magnesium is a significant element in the body, however, in clinical practice, magnesium and its deficiency effects may be neglected by the clinicians. Additionally, it has been subject to many clinical types of research in the past, and there is a growing tendency about magnesium its metabolic effects on the body. There have been conflicting studies about magnesium deficiency and its effects on diabetes frequency. According to a study of 127,832 subjects, the risk of developing T2DM increased with lower magnesium consumption [12], conversely, previously, Atherosclerosis Risk in Communities Study (ARIC) hadn’t found an association between magnesium intake and diabetes mellitus development in 12.000 subjects [13].
In the current study, we have found mean magnesium level very near to threshold level for magnesium deficiency, and 35.5 % of T2DM patients had hypomagnesemia which was predominantly common in female patients (72.1 % of hypomagnesemia T2DM patients). Consistently, a recent longitudinal Dutch study found that magnesium deficiency exacerbates diabetes in women, but not in men, and this study suggested that female hormones play a role in magnesium wasting [14]. Possible mechanisms for the relationship between magnesium deficiency and T2DM are based on the role of magnesium in insulin secretion and signaling. Since dependent on magnesium, magnesium deficiency can disturb insülin secretion phases through a direct or indirect route mediated by intracellular calcium pathways, and also magnesium blocks inositol 1,4,5-triphosphate (IP3)-gated calcium channel antagonist [15]. The KATP channels which play an important role in secretion have been to be opened in magnesium deficiency and insulin response to glucose had been found disturbed [16]. Recently a transporter protein called NIPAL1 (NIPA-like domain containing 1, which causes insülin secretion has been found downregulated by extracellular magnesium deficiency [17]. Furthermore impairment of tyrosine kinase activity in magnesium deficiency causes insulin signaling defect [18].
Despite higher magnesium deficiency, fasting blood glucose, and HbA1c levels were insignificantly higher in this study group, this was compatible with a Swiss study that didn’t find plasma magnesium levels in correlation with glycemic control [11], whereas a cross-sectional study of 101 T2DM patients has found HbA1c higher in magnesium-deficient patients, however, the p level was near to insignificant level and correlation was weak [19]. Also a study of 126 T2DM patients from Nigeria has found magnesium deficiency in relationship with HbA1c [20].
Hyperlipidemia, hypertension, and microalbuminuria were found higher in the current study, in vitro studies have shown that magnesium is essential for protection from vascular calcification [21, 22], likewise a recent Chronic Renal Insufficiency Cohort (CRIC) study showed that higher magnesium levels are associated with lower systolic and diastolic pressure, and higher progression to chronic kidney failure [23], and also Zahra et al. showed that diabetic nephropathy was found to be more common in DM patients [19]. One should focus on underlying mechanisms should focus on oxidative stress and vascular inflammation. In a study of diabetes patients, magnesium levels were positively correlated with glutathione peroxidase 3 (GPX-3) and negatively correlated with malondialdehyde (an oxidative stress marker) [24].
The results demonstrated in this work provide a new perspective on magnesium’s role in diabetes, in clinical practice hypertension and microalbuminuria have been important issues in diabetes. Magnesium deficiency has been common in type 2 DM and magnesium deficiency shouldn’t be neglected.
There are several strengths and limitations to this research. Its single-centered and cross-sectional style were the main limitations. The classification of magnesium deficiency was based on extracellular fluid level, however, this study size was not small, and evaluated associations of multiple components of T2DM disease according to magnesium deficiency.

Conclusions

Magnesium deficiency is not rare in T2DM, however, this deficiency didn’t affect blood glucose control at a significant level, on the other hand, hypertension, microalbuminuria and hyperlipidemia components of diabetes have been shown to increase with magnesium deficiency. Still more studies are needed to clarify and explain these results and relationships.
 
Received 02.02.2022
Revised 12.02.2022
Accepted 21.02.2022

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