Samozai, Devarapalli, and Babu: Study of serum copper and zinc levels in type-II diabetes mellitus patients


Introduction

Diabetes mellitus is one of the world’s most prevalent diseases. The whole world should be cautious and more attentive to the prevalence of the Diabetes mellitus and more particularly to the physiological and pathological changes that occur because of the increased blood sugar levels in the body. These physiological and pathological changes results in derangement of the functioning of the bodily activities which not only results in diseases, but also impairs in the healing process of the body. These effects of the prevalent diabetes mellitus makes the world more cautious about the diabetes. The International Diabetes Federation estimates a worldwide prevalence of 387 million (8.3%) and the global burden of Type-II diabetes is expected to increase 592 million by 2035.1, 2 The chronic hyperglycaemia of diabetes is associated with long term damage, dysfunction and failure of different organs, and these changes in turn lead to development of well-defined clinical entities, the so called complications, which may affect especially the eyes, kidneys, heart, blood vessels, the skin and the nervous system.3 The prevalence of diabetes mellitus is increasing in India also in people of all socio-economic status.

In the previous studies, it is found that the trace elements like copper and zinc, which act as cofactors for the essential enzymes, which are involved in many metabolic pathways, are found to be altered in the diabetics when compared to non-diabetics. Zinc (Zn) is one of the most important trace elements in the body. It is required for over 300 different cellular processes, including enzyme activity, protein synthesis and intracellular signalling.4 It is involved in homeostasis, in immune responses, in oxidative stress, in apoptosis and in ageing.5 Copper (Cu) is an essential trace element, capable of fluctuating between the oxidized Cu2+ and the reduced Cu+ state, being co-factor for many enzymes. This divalent cation is involved in SOD activity. Copper has the capacity to form covalent bounds and it takes part in many redox processes. Copper ions are involved in generation of reactive oxygen species through Fenton reaction, having a pro-oxidant action. Moreover, the deficiencies and the excess of Cu are associated with specific clinical manifestations.6

Materials and Methods

This present study was conducted at Dr.Patnam Mahender Reddy Institute of Medical Sciences, Chevella, Telangana after obtaining clearance from the Institutional Ethical Committee. This is an observational, prospective and case-control study which is conducted to assess the levels of Cu and Zn in relation to hyperglycaemia and HbA1c in the patients with uncomplicated T2DM. Newly diagnosed uncomplicated Type-II Diabetes Mellitus patients are selected as study group. Age and Sex matched healthy volunteers were recruited as control group. Inclusion criteria for the present study of subjects as group 1 patients having FPG≥126mg/dL and HbA1c≥6.5%. Exclusion criteria for all the groups was the persons known as smokers, alcoholics and subjects suffering with cancers, hypertension, renal and hepatic diseases, and any other acute/chronic illness; pregnant and post-menopausal females.

After obtaining informed written consent from both the groups, fasting venous blood was collected. A total of 6mL of blood is obtained from the subjects. 2mL of this blood was put in EDTA (Ethylene Diamine Tetra Acetic Acid) vacutainer for HbA1c estimation. Another 2mL of blood is put in fluoride vacutainer for blood glucose estimation and rest of the 2mL was transferred to plain vacutainer for estimation of Cu and Zn. Blood sample in EDTA vacutainers and Fluoride vacutainers was mixed properly. The blood sample in plain vacutainer was allowed to clot at 37ºC for 20min. Then, the plain vacutainers were centrifuged for 15 minutes at 3,000 rpm to obtain aliquots of serum which are stored at -20ºC for analysis of Cu and Zn levels. The fasting blood glucose level is estimated by fully automatic analyser (Transasia XL-640) using glucse oxidase-peroxidase method.7 HbA1c was analysed using ion exchange resin method. Cu and Zn were analysed using semi-autoanalyser (Erba Chem 5) using calorimeter method.8, 9

The observations were arranged in suitable tables for analysis under the relevant headings. The findings were averaged as (mean ± standard deviation) for each parameter subgroups separately. Each variable, including Serum levels of Cu (µg/dL), Zn (µg/dL), FBS (mg/dL) and HbA1C (%) were analysed by Paired Sample t-test. Statistical analysis was done using IBM SPSS Statistics 20 package. P value <0.05 was considered as statistically significant and p-value of <0.005 was considered as statistically highly significant.

Results

In our present study, we have observed that the levels of Cu, FBS and HBSAg were significantly changed in diabetic subjects when compared to non-diabetic control group. It is further found that the levels of Zn in diabetic and non-diabetics has not known shown any significant change. The mean Cu levels in diabetics is 99.98 and 99 in non-diabetics. Similarly the levels of Zn, FBS, HBSAg were found to be 66.30, 85.84; 140.78, 87.14; 6.60, 5.78 respectively in diabetic subject and non-diabetic control groups.

Table 1

Paired samples statistics between diabetic subjects and non-diabetic control group

Mean

N

Std. Deviation

Std. Error Mean

Cu (µg/dL)

Subjects

99.98

50

6.629

.937

Control

99.00

50

5.959

.843

Zn (µg/dL)

Subjects

66.30

50

8.162

1.154

Control

85.84

50

8.115

1.148

FBS(mg/dL)

Subjects

140.78

50

22.675

3.207

Control

87.14

50

6.174

.873

HbA1C (%)

Subjects

6.60

50

.495

.070

Control

5.78

50

.648

.092

Table 2

Paired samples correlations between diabetic subjects and non-diabetic control group

N

Correlation

Sig.

Cu (µg/dL)

50

.491

.000

Zn (µg/dL)

50

.159

.269

FBS(mg/dL)

50

.303

.032

HbA1C (%)

50

.420

.002

Table 3

Paired samples test between diabetic subjects and non-diabetic control group

Paired Differences

t

df

Sig. (2-tailed)

Mean

Std. Deviation

Std. Error Mean

95% Confidence Interval of the Difference

Lower

Upper

Cu (µg/dL)

.980

6.378

.902

-.832

2.792

1.087

49

.283

Zn (µg/dL)

-19.540

10.553

1.492

-22.539

-16.541

-13.093

49

.000

FBS(mg/dL)

53.640

21.618

3.057

47.496

59.784

17.545

49

.000

HbA1C (%)

.820

.629

.089

.641

.999

9.220

49

.000

Discussion

Hyperglycemia condition in diabetes have an considerable impact on the metabolism of Zinc and Copper. A number of studies with varied findings have been found stating deranged Copper and Zinc in diabetics. Bozkurt et al and Ferdousi et al. in their independent studies have noted a significant increase in the Cu levels in new cases of T2DM.10, 11 In the research work by Zargar et al, they found an increase in the serum copper levels in T2DM.12 But in our present study, we could not find any significant correlation between the increased serum levels of Cu in diabetics. Babalola et al also had noted a similar findings in their study.13

Altered levels of Zn in diabetics has been shown in number of studies done in the past. In the present study we have found significant decrease in the levels of Zn in subjects of diabetes mellitus. Our findings are similar to the findings of Ferdousi et al.11 Walter et al. also have recorded hyperzincuria in a 24 hour collected urine sample in the diabetic subjects with significant decreased levels of Zn and normal Mg levels.14

The levels of Cu can be measured as an early therapeutic measure of DM. It is well-known that higher levels of Cu may result in generation of free radicals through Fenton reaction, which in turn results in increased oxidative stress. Zn being important trace element for functioning of oxidoreductases, hydrolases, ligases and lyases.

Conclusion

T2DM is related to altered levels of trace elements like Zn, Cu. Zn can be better analysed from 24 hours collected urine sample. Early detection of the trace elements Cu, Zn is very useful in early detection of onset of T2DM along with factors like FBS, HBSAg. The study can be further made more appropriate by considering more trace elements in more number of subjects for a prolonged period of study. Once the T2DM is detected early or the stage of pre-diabetes is confirmed the subject can be prevented or delayed from the chance of occurrence of Diabetic.

Source of Funding

None.

Conflict of Interest

The authors declare no conflict of interest.

References

1 

International Diabetes Federation. IDF Diabetes atlas. In: IDF, eds. A Book. 6th ed. Brussels, Belgium: International Diabetes Federation; 2013.

2 

SA Kaveeshwar J Cornwall The current state of diabetes mellitus in IndiaAustralia Med J201471458

3 

J Braid JA Strong Diabetes mellitusDavidson’s Principle and practice of Medicine11th editionChurchill LivingstoneEdinburg1974676711

4 

SL Kelleher NH McCormick V Velasquez V Lopez Zinc in Specialized Secretory Tissues: Roles in the Pancreas, Prostate, and Mammary GlandAdv Nutr20112210111

5 

M Stefanidou C Maravelias A Dona C Spiliopoulou Oral antidiabetic agents: current role in type 2 diabetes mellitusArch Toxicol20068011910.1007/s00204-005-0009-5

6 

I Bremner Manifestation of copper excessAm J Clin Nutr199867106973

7 

P Trinder Determination of glucose in blood using glucose oxidase with an alternative oxygen acccetorAnnals Clin Biochem19696247

8 

A Abe S Yamashita A Nona Sensitive and direct calorimeter assay for copper in serumClin Chem Apr19893545524

9 

T Makino M Saito D Horiguchi K Kina A highly sensitive colorimetric determination of serum zinc using water-soluble pyridylazo dyeClin Chim Acta1982120112735

10 

F Bozkurt R Tekin S Gulsun O Satici O Deveci S Hosoglu The levels of copper, zinc and magnesium in type II diabetic patients complicated with foot infectionsIntern J Diabetes Dev Countries20133331659

11 

S Ferdousi AR Mia Serum levels of copper and zinc in newly diagnosed type-2 diabetic subjectsMymensingh Med J20122134758

12 

AH Zargar NA Shah SR Masoodi BA Laway FA Dar AR Khan Copper, zinc and magnesium levels in non-insulin dependent diabetes mellitusPostgrad Med J Nov1998748776658

13 

OO Babalola LO Ojo O Akinleye Status of the levels of lead and selected trace elements in type 2 diabetes mellitus patients in Abeokuta, NigeriaAfr J Biochem Res Dec20071712731

14 

RM Walter JY Uriu-Hare KL Olin MH Oster BD Anawalt JW Critchfield Copper, Zinc, Manganese and Manesium status and complications of diabetes mellitusDiabetes Care1991141110506



jats-html.xsl

© This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


  • Article highlights
  • Article tables
  • Article images

Article History

Received : 19-10-2021

Accepted : 13-11-2021

Available online : 07-12-2021


View Article

PDF File   Full Text Article


Copyright permission

Get article permission for commercial use

Downlaod

PDF File   XML File   ePub File


Digital Object Identifier (DOI)

Article DOI

https://doi.org/10.18231/j.ijcap.2021.067


Article Metrics






Article Access statistics

Viewed: 121

PDF Downloaded: 59



Open Abstract (Increase article citation) Wiki in hindi