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ORIGINAL ARTICLE
Year : 2019  |  Volume : 32  |  Issue : 3  |  Page : 910-915

The value of serum zinc in early detection of nephropathy in type 2 diabetic patients


1 Department of Internal Medicine, Faculty of Medicine, Menoufia University, Shebin El Kom, Egypt
2 Department of Nephrology, Madint Nasr Police Hospital, Cairo, Egypt

Date of Submission23-Oct-2017
Date of Acceptance17-Dec-2017
Date of Web Publication17-Oct-2019

Correspondence Address:
Mahmoud A Sakr
Shebin El Kom, Menoufia Governorate
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_709_17

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  Abstract 

Objective
The aim of this research was to study the value of serum zinc in early detection of nephropathy in patients with type 2 diabetes.
Background
Zinc is involved in multiple aspects of cellular metabolism. It is required for the catalytic activity of nearly 100 enzymes and it plays a major role in immunity, protein synthesis, wound healing, DNA synthesis, and cell division. Zinc is also important for normal growth and development during pregnancy, childhood, and adolescence, and is required for proper sense of taste and smell. A daily intake of zinc is required to keep a steady state because the body has no specialized zinc storage system. Zinc plays important role in the development and progression of type 2 diabetes. Zinc supplementation for 12 weeks can reduce albumin excretion in patients with diabetic microalbuminuria probably through antioxidative mechanisms.
Patients and methods
This case–control study was conducted on 100 participants classified into four groups: 25 healthy individuals (group I), 25 diabetic patients without albuminuria (group II), 25 diabetic patients with albuminuria (group III), and 25 nondiabetic patients with chronic kidney disease (group IV).
Results
Mean serum zinc level was found to be lower in group III (37.6 ± 15.92) compared with the control group (80.48 ± 12.06) and other patient groups, group II (50.28 ± 15.85) and group IV (39.72 ± 16.21), with a high statistical significance.
Conclusion
Low serum zinc levels were related to the development of diabetic nephropathy.

Keywords: albuminuria, biomarker, diabetic nephropathy, oxidative stress, zinc


How to cite this article:
Kora MA, Tawfeek AR, Sakr MA. The value of serum zinc in early detection of nephropathy in type 2 diabetic patients. Menoufia Med J 2019;32:910-5

How to cite this URL:
Kora MA, Tawfeek AR, Sakr MA. The value of serum zinc in early detection of nephropathy in type 2 diabetic patients. Menoufia Med J [serial online] 2019 [cited 2019 Nov 19];32:910-5. Available from: http://www.mmj.eg.net/text.asp?2019/32/3/910/268834




  Introduction Top


Diabetic nephropathy (DN) is a microvascular complication related to diabetes causing slow deterioration of renal function leading to end-stage renal disease (ESRD) [1]. The nephropathy associated with diabetes has been attributed to oxidative stress [2]. Oxidative stress can be caused either by the increased production of reactive oxygen species or a deficiency in antioxidant defense mechanism of the body. Antioxidant deficiency can result from decreased intake of vitamins, such as vitamins C and E, or impaired synthesis of enzymes, such as superoxide dismutase, catalase, and glutathione peroxidase, owing to zinc deficiency [3]. Chronic zinc deprivation leads to an increased sensitivity to the effects of oxidative stress because of deficiency of these enzymes [4]. It is not a clear which begins first: the effects of diabetes mellitus and hyperglycemia on zinc metabolism or the effects that follow changes in zinc homeostasis on carbohydrate metabolism. Perhaps more accurately, there are concurrent, semi-independent events that give rise to the effects of one on the other. Consequently, considering the possible modulating effects of serum zinc on antioxidant functions, a restored zinc status in patients with type 2 diabetes (T2D) mellitus might counteract the deleterious effects of oxidative stress and help to prevent the diabetic complications [5]. Although several factors are involved in the genesis of DN, low zinc status appears to contribute to the diabetes-associated renal injury [6]. Measurement of serum zinc levels may be considered necessary in diabetic patients and might be used as a marker of nephropathy with other nephropathy detection markers. Little is known, however, about the utility of serum zinc level in the assessment of nephropathy in diabetic patients [7]. A relationship between serum zinc and albuminuria has been observed in many studies for T2D [8]. In another study, there was an inverse zinc–microalbuminuria association, showing that advancing DN represented by decreasing glomerular filtration rate and increasing microalbuminuria is associated with decreased zinc levels [7]. There was high prevalence of zinc and copper deficiency in patients with nephrotic syndrome. Causes of hypozincemia and hypocuperemia were hypoalbuminemia and increased 24-h urinary albumin losses [9]. The aim of this work is to study the value of serum zinc in early detection of nephropathy in patients with T2D.


  Patients and Methods Top


The current study was carried out after obtaining a written consent from all patients and an approval by the faculty of medicine, Menoufia University Research Ethics Committee. This prospective case–control study was conducted on 100 individuals aged 40 years and older enrolled from Nephrology Department Madint Nasr Police Hospital during the period from November 2016 to March 2017. Inclusion criteria of the participants were; (1) patients who were diagnosed as T2D with albuminuria, (2) T2D patients without albuminuria, (3) nondiabetic chronic kidney diseased (CKD) patients such as those with hypertension and glomerulonephritis, and finally (4) healthy individuals as a control group. Patients will be omitted from the study according to the following exclusion criteria and include patients who showed evidence of liver cirrhosis or other liver diseases or hepatitis C virus antibody positive (steatosis and steatohepatitis are not excluded) and pregnant women. They were divided into four groups: the control group (group I) included 25 healthy individuals with no clinical signs or laboratory evidence of any disease, group II included 25 diabetic patients without albuminuria, group III included 25 diabetic patients with albuminuria, and group IV included 25 nondiabetic patients with CKD. Full history taking was done for the population group with stress on duration of diabetes and history of any kidney diseases. Complete clinical examination will be done including blood pressure and anthropometric measurements (e.g. weight, height, BMI). Laboratory investigations such as albumin/creatinine ratio in urine, complete blood count, liver enzymes (alanine transaminase, aspartate transaminase), hepatitis C antibody, renal profile (creatinine, urea), glucose profile [fasting plasma glucose (FG), postprandial glucose (PPG), glycated hemoglobin (HbA1c)], and lipid profile (total cholesterol, high-density lipoprotein, low-density lipoprotein, and triglycerides) were performed; all laboratory materials are from Delta Medical Company (Cairo, Egypt), and serum zinc assay kits are from Spinreact Company (Madrid, Spain).

Statistical analysis

The collected data were analyzed by statistical package of social science program (released 2011, IBM SPSS Statistics for Windows, version 20.0; IBM Corporation, Armonk, New York, USA). Qualitative data were expressed as number and percentage and analyzed by using χ2-test. Quantitative data were expressed as mean ± SD and analyzed using t-test.


  Results Top


The present study was conducted on 100 participants; Regarding age, sex, and BMI, the study revealed that patient groups (II, III& IV) showed a significant difference as regards age when it compared with controls (group I) (P = 0.034) [Table 1]. Age showed a significant increase in patient groups II and III compared with groups I and IV; it also showed no significant difference between groups I and IV (P = 0.86), a significant increase in group III compared with group I (P = 0.01), and a significant increase in group III compared with IV (P = 0.007) [Table 1]. BMI showed a significant increase in groups II and III compared with groups I and IV; it also showed no significant difference between groups II and III (P = 0.204), and groups and I and IV (P = 0.65), and a significant increase in group II compared with controls and group IV. Finally, it showed a significant increase in group II compared with controls and group IV [Table 1]. In serum levels of FPG, PPG, and HbA1c, it has been noticed that FPG, PPG, and HbA1c showed a significant increase in diabetic patient groups II and III compared with the control group (group I) and group IV (P = 0.001), and it also showed no significant increase in group III compared with group II (P = 0.1), and group IV; finally, it showed a significant increase in group II compared with group IV and controls [Table 2]. According to serum zinc level, it was noticed that serum zinc levels showed a significant decrease in all patient groups II, III, and IV compared with controls (group I) as follows, respectively: 80.4 ± 12.0, 50.28 ± 18.25, 37.6 ± 15.9, and 39.7 ± 16.2 (P = 0.001). It shows a significant decrease in groups III and IV than in group II. It also shows that there is no significant difference between groups III and IV [Table 3]. [Table 4] shows a correlation between zinc and urinary albumin/creatinine ratio in each group. In group I (controls), there is no significant correlation between albumin/creatinine ratio and serum zinc level (P = 0.17). In group II, there is no significant correlation between albumin/creatinine ratio and serum zinc level (P = 0.95). In group III, there is a significant negative correlation between albumin/creatinine ratio and serum zinc level (P = 0.003). In group IV, there is a significant negative correlation between albumin/creatinine ratio and serum zinc level (P = 0.001). Receiver operating characteristic (ROC) curve for serum zinc to diagnose diabetic patients with albuminuria showing that area under the curve is 0.747 which is significant and P value of 0.001 which is significant and cutoff of 54.5 with specificity 60% and sensitivity 80%. The receiver operating characteristic curve for serum zinc to diagnose diabetic patients without albuminuria shows nonsignificant results.
Table 1: Comparison between studied groups according to demographic data

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Table 2: Statistical significance between the studied groups according to serum level of fasting blood glucose (mg/dl), postprandial glucose (mg/dl), and glycated hemoglobin (%)

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Table 3: Statistical significance between the studied groups according to serum zinc level

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Table 4: Correlation between zinc and urinary albumin/creatinine ratio in each group

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  Discussion Top


DN is one of the common microvascular complications of diabetes mellitus. It is a leading cause of ESRD in developed and developing countries and a contributor to significant morbidity and mortality in diabetic patients [10].

The first step in the screening and diagnosis of nephropathy related to diabetes is to measure albumin in a spot urine sample. Screening should not be performed in the presence of conditions that increase urinary albumin excretion, such as urinary tract infection, hematuria, acute febrile illness, vigorous exercise, uncontrolled hypertension, and heart failure [11].

Albuminuria is the most widely used early clinical indicator of DN and has been recognized as a predictor of progression to ESRD in both type 1 and T2D. The changes between these albuminuria states represent a hallmark of the progression or regression of disease. More recent studies show that an increase in albuminuria, even within the range that is currently considered normal, indicates higher renal risk. In patients with T2D followed up for at least 5 years, higher albuminuria at baseline was associated with a faster decline in renal function [12].

Zinc is an important trace element with antioxidant properties. Furthermore, zinc deficiency has been documented in patients with CKD and also in patients with longstanding diabetes [13]. Zinc plays an important role in the development of both type 1 and T2D. Previous studies suggested that serum zinc level is associated with T2D, and loss-of-function mutations in zinc transporter-8 gene protect against T2D [14]. The patients with CKDs in the stages of chronic renal failure on conservative and dialysis treatment have a complex of metabolic abnormalities leading to serious complications [15]. Most of the authors stress on the fact that uremia 'per se' leads to an imbalance affecting the microelements in human body and the dialysis treatment is incapable to secure a full restoration of the required balance [16].

In the current study, we aim to evaluate serum zinc level as a marker for early detection of nephropathy in patients with T2D. To do that the present study included 100 participants divided into four groups as follows: 25 healthy individuals (group I), 25 diabetic patients without albuminuria (<30 mg/g creatinine) (group II), 25 patients with albuminuria (urinary albumin excretion rate of >30 mg/g) (group III), and 25 patients with CKD and not diabetics (group IV).

The present study showed that the age factor is significant with DN. In agreement with our result, Modarresi et al. found that duration of diabetes has a significant relationship with development and progression of DN and is an independent risk factor for DN, and this is consistent with most other related studies [17].

Our study showed no statistically significant relationships between DN and sex; however, United States Renal Data System annual [18] showed only a slight male predominance with a male-to-female incidence ratio of ESRD from DN of 1.1 : 1.

In our results, diabetic patient groups showed a significant increase in BMI when compared with control group and group IV; moreover, T2D patients without albuminuria showed a significant increase in BMI as compared with T2D patients with albuminuria. In agreement with our results, Kim et al. [19] found that BMI was significantly increased in T2D patient groups when compared with the control group.

The present study showed that in T2D patients with albuminuria there is a significant increase in the duration of diabetes when compared with T2D patients without albuminuria. Duration of diabetes is a very important factor in the development of DN as demonstrated in several studies such as that of Rudberg et al. [20], who reported that the longer the duration of diabetes, the higher the frequency of DN in a study of adolescents with a mean duration of disease of 10.9 years; they found that the duration of disease was an important factor in the overall severity of glomerulopathy. Overt nephropathy caused by glomerulosclerosis first appears 10–15 years after the onset of IDDM and after 5–10 years in patients with non-insulin-dependent diabetes mellitus.

The current study showed a significant increase in FPG, PPG, and HbA1c in T2D patients with albuminuria when compared with T2D without albuminuria. In addition, there is a significant increase in FPG, PPG, and HbA1c in the diabetic group without albuminuria when compared with the control group and group IV. This is in agreement with the study of Kumar et al. [21], who studied the correlation of DN and HbA1c in newly diagnosed T2D patients and found that mean FPG levels and HbA1c of population with macroalbuminuria and microalbuminuria were higher as compared with the population without albuminuria, and correlation was found to be extremely significant; this shows that FPG and HbA1c are positively associated with the incidence of DN in the population. Such findings support that the lack of tight glycemic control is a risk factor for developing diabetic complications such as DN, and the lower the HbA1c value obtained the lower the risk for development of microalbuminuria as Fraser and Phillips [22] show similar results.

Regarding our results, serum creatinine level showed only a significant increase in T2D patients with albuminuria when compared with the control group. Similar to our results, Kumar et al. [21] found that mean serum creatinine levels of populations with macroalbuminuria and microalbuminuria were higher as compared with the population without albuminuria, and the correlation was found to be extremely significant. This shows that serum creatinine is positively associated with the incidence of DN in the population.

In the present study, serum zinc level showed a significant decrease when T2D patients without albuminuria and T2D with albuminuria were compared with the control group. Similar to our results, the results of Al-Timimi et al. [7] showed that zinc deficiency often occurs in patients with diabetes. Therefore, the relationship between zinc status and progression of nephropathy in diabetes appears obviously.

Our results show that there is a significant decrease in serum zinc level among diabetic groups than in other groups. In T2D patients with albuminuria, the decrease in their serum zinc level was more when compared with its level in T2D patients without albuminuria. The study by Parham et al. [6] shows that although several factors are involved in the genesis of DN, low zinc status appears to contribute to the diabetes-associated renal injury and is in agreement with the study by Al-Timimi et al. [7], which shows that significantly low levels of serum zinc were observed in diabetic patients as compared with nondiabetic controls. The present study shows that serum zinc levels show a significant decrease in T2D patients with albuminuria compared with diabetic patients without albuminuria. This means that diabetic patients with low serum zinc level have a greater risk for developing DN in the future than those who have normal serum zinc level, and shows that measurement of serum zinc levels may be considered medically necessary in diabetic patients and might be used as a marker of nephropathy in concomitants with other nephropathy detection markers. Little is known, however, about the utility of serum zinc level in the assessment of nephropathy in diabetic patients.

Our study shows that there is a significant decrease in serum zinc level in patients with CKD and not diabetics. This is in agreement with the study by Yilmaz et al. [23], which shows decreased plasma zinc in CKD patients. In contrast to our study, Smythe et al. [24] found no significant difference in tissue concentrations of zinc between healthy controls and patients with CKD.


  Conclusion Top


On the basis of our results, we concluded that DM patients with albuminuria showed a decrease in serum zinc levels compared with nonalbuminuric diabetic and nondiabetic CKD patients. These results suggested that diabetic patients with decreased serum zinc level are at a high risk for developing DN, and serum zinc levels could be useful markers in early detection of albuminuric DN in T2D mellitus patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



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



 

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