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 Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 35  |  Issue : 3  |  Page : 344-349

Biochemical relations between copper, selenium, zinc, and magnesium with the glycemic state of diabetic pregnant women


1 Fellow in biochemistry, Clinical Pathololy Department, Benha University, Benha, Egypt
2 Pediatrics Department, Tanta University, Tanta, Egypt
3 Biochemistry Department, Faculty of Veterinary Medicine, Benha University, Benha, Egypt

Date of Submission22-Nov-2017
Date of Acceptance18-Sep-2018
Date of Web Publication07-Jan-2019

Correspondence Address:
Dr. Raafat R Mohammed
Benha University, Benha, Qalubia, Benha 13111
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/bmfj.bmfj_213_17

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  Abstract 


Background Micronutrients, have specific roles in the metabolism, normal growth, and the pathogenesis and progress of diseases with a specific alteration in diabetic patients.
Aim The present study aims to follow up the levels of urinary and serum copper, selenium, zinc, and magnesium (Cu, Se, Zn, and Mg) of pregnant diabetic primigravida and multigravida (second and third pregnancy) women compared with their levels in healthy nondiabetic pregnant ones and their possible association with the glycemic status.
Patients and methods Three groups of pregnant diabetic, primigravida women, second pregnancy and third pregnancy with their corresponding nondiabetic pregnant controls were followed up in this study.
Results The results of this study showed that the urinary levels of Cu, Se, Zn, and Mg were significantly higher in diabetic pregnant women when matched with healthy controls in all durations of sample collection at the first day of the third, sixth, and ninth months of pregnancy. The results are highly significant at multigravida (second and third pregnancy) than the primigravida ones. However, serum (Cu, Se, Zn, and Mg) levels were decreased all over the pregnancy periods.
Conclusion The results confirmed that alterations of urinary levels of Cu, Se, and Zn are associated with diabetes mellitus.

Keywords: diabetic pregnant women, selenium, trace elements, urine and serum copper, zinc and magnesium


How to cite this article:
Mohammed RR, Mehrez MM, Abdel-Maksoud H. Biochemical relations between copper, selenium, zinc, and magnesium with the glycemic state of diabetic pregnant women. Benha Med J 2018;35:344-9

How to cite this URL:
Mohammed RR, Mehrez MM, Abdel-Maksoud H. Biochemical relations between copper, selenium, zinc, and magnesium with the glycemic state of diabetic pregnant women. Benha Med J [serial online] 2018 [cited 2019 Dec 15];35:344-9. Available from: http://www.bmfj.eg.net/text.asp?2018/35/3/344/249422




  Introduction Top


Diabetes mellitus (DM) is a serious chronic worldwide group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin production, insulin secretion, and insulin signaling. The chronic hyperglycemia of diabetes is associated with long-term damage, dysfunction, and failure of various organs, especially the eyes, kidneys, nerves, heart, and the blood vessels [1],[2].

In 2013, 382 million people had diabetes; this number is expected to rise to592 millionby 2035 [3] suspected that the worldwide number of diabetic patients will increase further from 171 million people suffering from diabetes in 2000 to 592 million people by 2035. It was stated that diabetes remains the major public health issue in Egypt at 2010, reaching 4.787 million Egyptians, which will increase to 8.615 million by 2030 [4].

Gestational diabetes is any degree of glucose intolerance with onset or first recognition during pregnancy. The definition applies regardless of whether insulin or only diet modification is used for treatment or whether the condition persists after pregnancy [5].

Pregnant women with any type of diabetes will have a number of complications if they do not carefully monitor and manage their condition. So women with type 1 or type 2 diabetes should achieve target glucose levels before conception. High blood glucose during pregnancy can lead to the fetus putting on excess weight. This leads to problems in delivery, and a sudden drop in blood glucose for the child after birth. Children who are exposed for a long time to high blood glucose in the fetal live period are at higher risk of developing diabetes in the future [3].

Copper (Cu) is one of the essential trace elements, and has a particular role at the terminal end of the mitochondrial electron transport chain in cytochrome oxidase function [6].

High serum selenium (Se) levels were positively associated with the prevalence of diabetes complications [7].

Zinc (Zn) is required as a component of enzymes and plays an important role in the maintenance of several tissue functions, such as the synthesis, storage, release, and conformational integrity of insulin monomers. So its deficiency has now been recognized to be associated with many chronic illnesses such as DM which affects Zn homeostasis [8].

Magnesium (Mg) is a cofactor in both the glucose transporting mechanism of cell membranes and various enzymes important in carbohydrate oxidation. Its metabolism might be altered in patients with DM [9].

Micronutrient deficiencies are frequently associated with chronic hyperglycemia which causes significant alterations which directly modulate glucose homeostasis [8],[9]. Deficiencies of Mg, Zn, and Cu have been shown to predispose a person to glucose intolerance and to promote the development of diabetic complications [10].

The present study was designed to evaluate the urinary and serum levels of Cu, Se, Zn, and Mg of pregnant diabetic primigravida and multigravida (second and third pregnancy) women compared with their levels in healthy nondiabetic pregnant ones and their possible association with glycemic status.


  Patients and methods Top


Patients

The samples collected for the present study were carried out on six groups of pregnant women who came for follow up of pregnancy at the gynecology and family planning departments in Benha University Hospital, through 3 years (2015, 2016, 2017). The study protocol was approved by the Local Ethical Committee and only women who signed a written fully informed consent were included in the study. They were classified into:
  1. Group I : (control − primigravida) consists of 15 nondiabetic primigravida women.
  2. Group II: consists of 15 diabetic primigravida women.
  3. Group III: (control − second pregnancy) consists of 15 nondiabetic (multigravida at the second pregnancy) women.
  4. Group IV: consists of 15 diabetic multigravida (at the second pregnancy) women.
  5. Group V: (control − third pregnancy) consists of 15 nondiabetic multigravida (at the third pregnancy) women.
  6. Group VI: consists of 15 diabetic multigravida (at the third pregnancy) women.


Medical history

All the recipients have no complaint other than follow-up pregnancy.

Criteria for diagnosis

The criteria for the diagnosis of type two DM conclude that any one of the following is diagnostic:
  1. Classical symptoms of diabetes, polyuria, polydipsia, and fatigue, with plasma random glucose levels being more than or equal to 200 mg/dl regardless of the time of the preceding meal.
  2. Fasting plasma glucose levels are more than or equal to 116 mg/dl without caloric intake for at least 8 h.
  3. Two-hour postprandial plasma glucose levels are more than or equal to 200 mg/dl during the oral, glucose tolerance test.


Sample collection

Blood and urine samples were collected at the first day of the third, sixth, and ninth month of pregnancy.

About 3 ml venous blood was obtained using a disposable needle and syringe. Each sample was centrifuged at 4000 rpm and the serum was separated and used freshly for the estimation of concentrations of glucose, Cu, Se, Zn, and Mg.

The freshly voided urine samples were collected in acidified containers for 24 h. They were used freshly for the estimation of concentrations of Cu, Se, Zn, and Mg.

Biochemical analysis

Determination of blood sugar

Serum glucose was measured by the enzymatic method using commercial kits according to Trinder [11].

Determination of urinary and serum copper, selenium, zinc, and magnesium levels

Urinary and serum Cu, and Se were determined by inductively coupled plasma atomic emission spectroscopy according to Isaac and Ihnat [12].

Urinary and serum Zn were determined according to Johnsen and Eliasson [13].

Levels of urinary Mg were determined according to Jacob [14].

Statistical analysis

The statistical analysis was carried out using analysis of variance and Student’s t test was used to compare quantitative variables. The P value was considered significant if P value is less than 0.05 using SPSS (version 19) by International Business Machines Corp. (IBM, New York, New York, USA).


  Results Top


The presented data showed that urinary Cu and Se were significantly increased (P<0.05) at the first day of the third and sixth months of diabetic pregnant women in comparison with the levels of control nondiabetic pregnant ones, which became very highly significantly increased (P<0.001) at the ninth month of pregnancy.

Urinary Zn and Mg were very highly significantly increased (P<0.001) in all periods of sample collected during pregnancy of diabetic women.

The present data revealed that the serum levels of Cu, Se, Zn, and Mg were decreased significantly (P<0.05) at the third month of pregnancy and then highly significantly decreased (P<0.01) at the sixth month and then they became very highly significantly decreased (P<0.001) at the ninth month of diabetic pregnant women in comparison with the levels of control in nonpregnant ones ([Table 1],[Table 2],[Table 3],[Table 4],[Table 5],[Table 6]).
Table 1 Mean values of urinary copper, selenium, zinc, and magnesium in diabetic pregnant women at the first day of the 3rd month of pregnancy in comparison with the levels of control nondiabetic pregnant women

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Table 2 Mean values of urinary copper, selenium, zinc, and magnesium in diabetic pregnant women at the first day of the sixth month of pregnancy in comparison with the levels of control nondiabetic pregnant women

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Table 3 Mean values of urinary copper, selenium, zinc, and magnesium in diabetic pregnant women at the first day of the ninth month of pregnancy in comparison with the levels of control nondiabetic pregnant women

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Table 4 Mean values of serum copper, selenium, zinc, and magnesium in diabetic pregnant women at the first day of the third month of pregnancy in comparison with the levels of control nondiabetic pregnant women

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Table 5 Mean values of serum copper, selenium, zinc, and magnesium in diabetic pregnant women at the first day of the sixth month of pregnancy in comparison with the levels of control nondiabetic pregnant women

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Table 6 Mean values of serum copper, selenium, zinc, and magnesium in diabetic pregnant women at the first day of the ninth month of pregnancy in comparison with the levels of control nondiabetic pregnant women

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  Discussion Top


It has been accepted that micronutrients are essential for optimal health. And it is confirmed that in the initial phases of diabetes, there are disturbances in the metabolism of Cu, Se, Zn, Mg, and some other trace elements [15]. It was found that changes in serum levels of Zn, Mg, and Se occur at the prediabetic stage and precedes the development of diabetes and may be responsible for medical complications that are recently reported at this stage [16].

Copper

The results showed significant decrease in serum Cu levels during the entire duration of pregnancy in diabetic pregnant women than control nondiabetic ones.

The results are similar to some studies [17],[18]. But the results were at variance with other studies [19].

The decrease in serum Cu concentration is related to the increased demand of the gravidas babies and is also been linked to disorders in the structure of the arterial wall, stress, infection, and DM [20],[21].

Also this study showed a significant decrease in serum Cu through pregnancy in diabetes might be due to the increased oxidative stress in diabetes with increasing fetal age. Also free radicals have important roles in the pathogenesis of diabetes and a relationship between oxidative stress and secondary complications of diabetes exists [22],[23].

On the contrary, some studies showed no significant difference between urine Cu levels in diabetics and control groups [15].

High urinary Cu may be a marker of high renal tissue Cu, as evidenced by animal studies, in which Cu chelation improved markers of renal damage [22].

Also a lot of diabetic patients with microalbuminuria have increased urinary Cu excretion which however does not exclude the potential toxic effects of this high Cu excretion on the progression of diabetic nephropathy [24]. Microalbuminuria can increase with the duration of diabetes, thus causing an increase in urinary Cu.

Selenium

The decreases in serum and an increase in urinary Se levels during pregnancy in diabetic pregnant women when compared with control nondiabetic pregnant women are similar to some studies [25],[26],[27].

These changes in serum and urinary Se concentration might be due to its presence in the plasma, which is required for normal pancreatic functions and have an important role in vitamin E metabolism. There are intrinsic enzymatic and nonenzymatic antioxidant-detoxifying mechanisms that decrease reactive oxygen species concentrations in the human body. Overproduction of peroxides along with decrease of the antioxidant defense system causes oxidative damage and these events in type 2 diabetic patients are observed earlier before diabetic complications develop [28].

Moreover, these results were confirmed with other studies [29] which stated that serum Se levels of diabetic patients were decreased compared with controls. The results were also at variance with the studies [25] which reported that serum Se levels of diabetic patients were unchanged compared with controls.

Urine Se instead was very highly significantly increased in the ninth month of pregnancy of diabetic women; these results are similar to some studies [30] which stated that diabetics have significantly lower serum Se and higher urinary trace elements and diabetic women have significantly lower serum Zn and Se and lower urinary Mg and Zn than diabetic men.

Zinc

The results showed a significant decrease in urinary and serum Zn level in diabetic pregnant women than control in women in all durations of pregnancy.

The results are similar to some studies [31],[32] which stated that the serum Zn level was significantly lower in diabetic patients as compared with controls. The possible explanation of hypozincemia observed in diabetics might be due to decreased gastrointestinal absorption of Zn.

It was stated that the lower serum levels of Zn observed in diabetic men may be attributed to increased urinary excretion of these elements. The lower serum Zn levels may also be associated with additional urinary loss of Zn in diabetic pregnant women [33].

This is also in agreement with the studies [30] which stated that serum Zn level decreased with increased duration of diabetes. Also the decreased serum levels may be attributed to the increased urinary loss of these trace elements.

Moreover, the recorded decreases in serum element levels might be attributed to hormonal imbalance associated with the diabetes state [34].

Magnesium

The results showed a significant decrease in urinary and serum Mg in diabetic individuals than control in all duration of pregnancy of diabetic women. These results are similar to the studies [35],[36] which found that serum Mg levels were significantly low in the diabetics as compared with nondiabetic pregnant women.

But the recorded results were at variance with other studies [37] which stated that there were no significant differences in serum Mg between groups.

Mg is excreted at higher than normal rates in the urine of diabetic patients. The polyuria of diabetes resulting from hyperosmotic glomerular filtrate is largely responsible for enhanced urinary mineral loss [36].Thus hypermagnesuria in diabetics have been attributed to osmotic diuresis. Glycosuria which accompanies the diabetic state impairs renal tubular reabsorption of Mg from the glomerular filtrate and likely contributes to the high frequency of hypomagnesemia in poorly controlled diabetics [38].

In this respect, it was stated that the decreased serum Mg levels may be attributed to the increased urinary loss of these trace elements. Reductions in renal functions with increasing duration of diabetes have been implicated in urinary trace element loss [34].

Finally, it was declared that diabetes enhances urinary loss of these elements, while lower serum Zn and Se and higher urinary Mg and Zn excretion were associated with the fetal age-related differences might be attributed to the hormonal imbalance associated with the diabetic state [39].


  Conclusion Top


The findings of the present study demonstrated that impaired trace-elements metabolism may have a role in the pathogenesis and progression of diabetes-associated complex disorders during pregnancy.

Supplementations of trace elements and antioxidants may be useful and beneficial in the treatment of complex disorders and help in preventing complications. Thus careful monitoring of these parameters in pregnant women is recommended.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

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