Journal of Diabetes Mellitus, 2021, 11, 41-51

https://www.scirp.org/journal/jdm
ISSN Online: 2160-5858
ISSN Print: 2160-5831

Association between Liver Enzymes and

Dyslipidemia in Yemeni Patients with
Type Two Diabetes Mellitus

Lotfi S. Bin Dahman1*, Mariam A. Humam1, Omer H. Barahim1, Omer M. Barahman2,

Mohamed A. Balfas3
1
Medical Laboratory Sciences Department, College of Medicine and Health Sciences, Hadhramout University, Mukalla, Yemen
2
Medicine Department, College of Medicine and Health Sciences, Hadhramout University, Mukalla, Yemen
3
Basic Medical Sciences, College of Medicine and Health Sciences, Hadhramout University, Mukalla, Yemen

How to cite this paper: Bin Dahman, L.S., Abstract

Humam, M.A., Barahim, O.H., Barahman,
O.M. and Balfas, M.A. (2021) Association The correlation between liver enzymes and lipid profile in T2D patients in the
between Liver Enzymes and Dyslipidemia Yemeni population has been evaluated. This is a case-control study comprising
in Yemeni Patients with Type Two Di-
142 T2D patients and 142 healthy control subjects were carried out at the out-
abetes Mellitus. Journal of Diabetes Melli-
tus, 11, 41-51. patient clinics of Ibn-Sina hospital, Mukalla, during the period from January to
https://doi.org/10.4236/jdm.2021.112004 May 2020. Serum fasting blood glucose (FBG), total cholesterol, triglyceride,
high-density lipoprotein cholesterol (HDL-C), alanine aminotransferase (ALT),
Received: January 11, 2021
aspartate aminotransferase (AST), and gamma-glutamyltransferase (GGT)
Accepted: March 23, 2021
Published: March 26, 2021 were analyzed using the Cobas Integra Plus 400 autoanalyzer. Also, anthro-
pometric and blood pressure measurements were taken from each partici-
Copyright © 2021 by author(s) and pant. Independent sample T-test and Pearson correlation coefficient were
Scientific Research Publishing Inc.
used. T2D patients had significantly higher FBG (P ≤ 0.0001), total cholester-
This work is licensed under the Creative
Commons Attribution International ol (P ≤ 0.0001), LDL-C (P ≤ 0.0001), and GGT (P ≤ 0.0001) while HDL-C was
License (CC BY 4.0). significantly lower in T2D patients (P = 0.021). In correlation analysis, serum
http://creativecommons.org/licenses/by/4.0/ GGT was positively associated with FBG (r = 0.216; P ≤ 0.0001), total choles-
Open Access terol (r = 0.196; P = 0.0001), triglyceride (r = 0.123; P = 0.038), and LDL-C (r
= 0.209; P ≤ 0.0001). Also, serum ALT was positively associated with FBG (r
= 0.145, P = 0.014) and triglyceride (r = 0.172, P = 0.004). In conclusion,
higher levels of ALT and GGT are used as the predictive biomarkers for
NAFLD in T2D patients with hyperlipidemia. Thus, routine screening of liver
enzymes and lipid profile in T2D patients is recommended for the early de-
tection of liver abnormalities and diminish diabetes complications.

Keywords
Liver Enzymes, Dyslipidemia, Type 2 Diabetes Mellitus, Yemeni Patients

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L. S. Bin Dahman et al.

1. Introduction
Diabetes mellitus is a metabolic disorder characterized by chronic hyperglycemia
which results from defective insulin action and secretion or both [1]. World
Health Organization projects that the number of diabetic patients will exceed
350 million by 2030 [1]. Previous data have documented liver disease is a major
cause of morbidity and mortality of type 2 diabetes patients [2] [3]. It is well
known that the liver is a vital organ in the metabolism of carbohydrates and in
maintaining glucose homeostasis during fasting and postprandial period [2] [4].
Non-alcoholic fatty liver disease (NAFLD) is the scope of chronic liver disease
in T2D patients [5], which is characterized by excess deposition of fat in the liver
and associated with hepatic insulin resistance [3] and T2D risk [5]. Serum ala-
nine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) are good
biomarkers of NAFLD. ALT has been considered the specific marker of liver in-
jury, as found in high concentrations in hepatocytes [6], while GGT is present
on the surface of most cell types and highly active in the liver, kidneys, and pan-
creas [7]. Also, GGT is responsible for extracellular glutathione catabolism and
may be linked to oxidative stress [8] and chronic inflammation [9]; both oxida-
tive stress and chronic inflammation are important pathways for hepatic insulin
resistance (IR) and subsequently T2D development [10].
Hyperinsulinemia and IR play an important role in lipid abnormalities for
T2D patients [2] [11]. Also, altered lipoprotein patterns and liver enzymes have
been identified as independent risk factors for the development of cardio-
vascular disease (CVD) [10] [11] [12]. Moreover, higher levels of triglycerides,
LDL-C, total cholesterol, and lower levels of HDL-C were reported in T2D pa-
tients than normal healthy subjects [13]. However, few studies reported the cor-
relation between liver enzymes and lipid profile in T2D patients; hence this
case-control study was conducted to assess the association between liver en-
zymes and blood lipid profile in a sample of Yemeni patients with T2D.

2. Subjects and Methods

2.1. Study Design and Subjects Selection
This is a case-control study was carried out at the College of Medicine and
Health Sciences, Hadhramout University, and the subjects were selected from
the diabetic outpatient clinic of Ibn-Sina hospital, Mukalla during the period
from January to May 2020. A total of 284 Yemeni adult subjects, randomly se-
lected, and recruited into this study. At recruitment, an in-person interview was
conducted using a structured questionnaire to collect health-related information.
The study group was subdivided into two groups: 142 healthy control subjects
composed of 51 males and 91 females (age: 46.0 ± 7.94 yr.), and 142 T2D pa-
tients composed of 64 males and 78 females (age: 54.0 ± 8.29 yr.). T2D patients
were those who reported being diagnosed with T2D. Healthy control subjects
were selected from the remaining participants who were free of T2D and were
matched for age, sex, and dialect group with cases on a 1:1 ratio. Moreover, the

DOI: 10.4236/jdm.2021.112004 42 Journal of Diabetes Mellitus

 L. S. Bin Dahman et al.

selected healthy control subjects were screened for the presence of undiagnosed
T2D at the time of blood donation by measuring fasting blood glucose (FBG).
Written consent was obtained from each participant entered into the study. The
study was approved by the Ethics Committee of the Medicine and Health Sciences
College, Hadhramout University, Mukalla, Yemen. Patients with co-morbidities
such as chronic liver disease, chronic renal disease, cardiovascular disease, and
malignancy were excluded.

2.2. Data Collection

A questionnaire form focusing on demographic information and diabetes histo-
ry was given to all subjects. The patient’s demographic information, clinical
presentation, medical history, and physical findings were taken from each sub-
ject. This included the patient’s age, sex, smoking status (never, current or past),
hypertension status (yes or no), diabetes status (yes or no) diabetes duration
(years), diabetes medication, and diabetes complications. Patients were diag-
nosed with diabetes based on medical history, present intake of diabetes medica-
tions, or according to the American Diabetes Association (ADA) criteria [14].
Patients with T2DM were defined as fasting blood glucose level ≥ 126 mg/dl (≥
7.1 mmol/L), 2-hour postprandial plasma glucose level ≥ 200 mg/dl (≥11.1
mmol/L) or HbA1c ≥ 6.5% [14]. Classification of Body Mass Index (BMI) was
based on the World Health Organization [15].

2.3. Anthropometric and Blood Pressure Measurements

Weight and height were measured following measured according to WHO
guidelines [15]. Body mass index (BMI) was calculated as weight/height2 (Kg/m2).
Obese subjects were defined as BMI ≥ 30 kg/m2 and normal-weight subjects
having a BMI of 18-25 according to WHO guidelines [15]. Patients who had a
blood pressure of ≥ 140/90mmHg or were taking antihypertensive medications
were diagnosed with hypertension [16]. A true healthy normal ALT level ranges
from 29 to 33 IU/l for males, and 19 to 25 IU/l for females and levels above this
should be assessed as described by the American College of Gastroenterology
(ACG) [17].

2.4. Biochemical Investigations

Ten milliliters of the venous blood sample was obtained from consenting sub-
jects. The blood samples were collected by vein puncture in tubes without anti-
coagulant. The blood samples were then transported to the laboratory imme-
diately. The serum was separated and stored at −20˚C freezers till analyses. The
serum samples of matched case–control pairs were randomly placed next to each
other with the case/control status blinded to the laboratory personnel and were
processed, and tested in the same batch. All laboratory equipment was cali-
brated. Thawing freezing was avoided by dividing the samples into aliquots.
Plasma fasting blood glucose (FBG), total cholesterol, triglycerides, and HDL-

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L. S. Bin Dahman et al.

cholesterol (HDL-C) were determined enzymatically using a chemical autoana-

lyzer (Cobas Integra 400 Plus, Roche diagnostic GmbH, Mannheim, Switzer-
land), following the standard procedures as described by the manufacturer.
Concentrations of LDL-cholesterol (LDL-C) were calculated using Friedwald’s
formula [18]. All biochemical investigations were analyzed in the National Cen-
ter for Public Health Labs-Mukalla, Yemen.

2.5. Statistical Analysis

Data were analyzed using the Statistical Package for the Social Sciences for
Windows (version 24) and are expressed by mean ± standard deviation (SD) for
continuous variables (normally distributed). Non-continuous variables are ex-
pressed by median (inter-quartile range) and n (percentage) for categorical va-
riables. Independent Student’s t-test used for normally distributed continuous
variables and Wilcoxon signed-rank test for skewed continuous variables. The
Pearson correlation test was performed with ALT, AST, and GGT as the depen-
dent variables. The statistical analysis was conducted at a 95% confidence level
and a P -value < 0.05 was considered statistically significant.

3. Results
Descriptive statistics of anthropometric and biochemical data of the study pop-
ulation are presented in Table 1. T2D patients had significantly increased BMI
(P = 0.008), systolic BP (P ≤ 0.0001), diastolic BP (P ≤ 0.0001), FBG (P ≤
0.0001), total cholesterol (P ≤ 0.0001), LDL-C (P ≤ 0.0001), and GGT (P = 0.016)
as compared to healthy control subjects. No significant difference was found in
serum triglyceride (P = 0.097) and ALT (P = 0.07). Healthy control subjects had
significantly increased HDL-C (P = 0.021) and AST (P = 0.001) as compared to
T2D patients. On the other hand, 31.7% of T2D patients had hypertension,
whereas, 6.3% of healthy control subjects had hypertension. Besides, in T2D pa-
tients, the current smokers were 4.2% and the former smokers were 3.5%. Ac-
cording to BMI criteria, 38.7% of T2D patients had overweight and 24.6% with
obese as compared to healthy control subjects (40.1%, 14.1%) respectively.
Pearson correlation using ALT, AST, and GGT as dependent variables is pre-
sented in Table 2. Serum ALT was positively associated with FBG (r = 0.145, P =
0.014), triglyceride (r = 0.172, P = 0.004), AST (r = 590, P ≤ 0.001), and GGT (r
= 0.507, P ≤ 0.001) respectively. Serum GGT was positively associated with sys-
tolic BP (r = 0.134, P = 0.024), diastolic BP (r = 0.218, P ≤ 0.001), FBG (r =
0.216, P ≤ 0.0001), total cholesterol (r = 0.196, P = 0.0001), triglyceride (r =
0.123, P = 0.038), LDL-cholesterol (r = 0.209, P ≤ 0.0001), and AST (r = 0.366, P
≤ 0.0001) across the combined group.
Using partial correlation analysis (Table 3), controlling for age and BMI, sig-
nificant positive association between ALT with AST (r = 0.589, P ≤ 0.0001) and
ALT (r = 0.514, P ≤ 0.0001) remained significant across the combined group,
whilst, the association between ALT with FBG and triglyceride was no longer

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 L. S. Bin Dahman et al.

significant. Using the same analysis, the association between GGT with systolic
BP (r = 0.124, P = 0.038), diastolic BP (r = 0.213, P ≤ 0.0001), FBG (r = 0.213, P
≤ 0.0001), total cholesterol (r = 0.199, P = 0.001), triglyceride (r = 0.127, P =
0.033), and LDL-C (r = 0.208, P ≤ 0.0001) remained significant before and after
age and BMI as adjustment.

Table 1. Anthropometric and biochemical data of healthy controls and T2D patients.

Variables Healthy controls T2D patients P-value

N 142 142

Age (years) 46.0 ± 7.94 54.0 ± 8.29 <0.0001

Sex: male/female 51 (35.9)/91 (64.1) 63 (44.4)/78 (54.9)

Weight (kg) 71.12 ± 10.67 69.61 ± 13.83 <0.0001

Height (cm) 164.57 ± 8.47 159.97 ± 10.04 <0.0001

BMI (kg/m2) 26.31 ± 3.95 27.21 ± 4.94 0.008

SBP (mmHg) 115.28 ± 13.11 128.80 ± 20.92 <0.0001

DBP (mmHg) 70.45 ± 9.02 79.47 ± 9.90 <0.0001

BMI classification:
Normal weight 65 (45.8) 52 (36.6)
Overweight 57 (40.1) 55 (38.7)
Obese 20 (14.1) 35 (24.6)

History of hypertension:
Yes/no 9 (6.3)/133 (93.7) 45 (31.7)/97 (68.3)

Smoking status:
Never Smoker 142 (100) 131 (92.3)
Current Smoker 0 (0) 6 (4.2)
0 (0) 5 (3.5)
Former Smoker

FBG (mmol/L) 5.18 ± 0.91 8.91 ± 2.89 <0.0001

Total cholesterol (mmol/L) 4.70 ± 0.77 5.16 ± 1.20 <0.0001

Triglyceride (mmol/L) 1.24 ± 0.37 1.16 ± 0.42 0.097

HDL-C (mmol/L) 1.67 ± 0.42 1.57 ± 0.34 0.021

LDL-C (mmol/L) 2.77 ± 0.80 3.35 ± 1.17 0.001

ALT (IU/L) 13.1 (8.37 - 19.3) 11.6 (7.3 - 16.8) 0.07

AST (IU/L) 21.2 (17.8 - 28.7) 16.4 (13.3 - 21.7) 0.001

GGT (IU/L) 25.1 (16.8 - 34.7) 29.2 (18.4 - 49.7) <0.0001

Data were presented as mean ± SD for normal continuous variables and median (interquartile range) for
continuous non-normal variables. Independent sample T-test for normally distributed continuous variables
and Mann-Whitney U test for skewed continuous variables. P-value < 0.05 was considered statistically sig-
nificant. BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; FBG, fasting
blood glucose; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol;
ALT, alanine aminotransferase; AST, aspartate aminotransferase; GGT, gamma-glutamyltransferase.

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L. S. Bin Dahman et al.

Table 2. Pearson correlation using ALT, AST and GGT as dependent variables in the
combined study group.

N = 284 ALT AST GGT

r P-value r P-value r P-value
Age (years) −0.046 0.443 0.010 0.860 0.047 0.433
Sex (M/F) 0.119 *
0.046 0.116 0.050 0.016 0.789
Weight (kg) −0.001 0.989 −0.008 0.895 −0.004 0.945
Height (cm) 0.098 0.101 0.071 0.235 −0.058 0.334
BMI (kg/m2) −0.070 0.241 −0.059 0.326 0.033 0.538
SBP (mmHg) −0.037 0.533 −0.058 0.334 0.134* 0.024
DBP (mmHg) 0.013 0.830 −0.080 0.178 0.218 **
<0.001
FBG (mmol/L) 0.145 *
0.014 −0.067 0.260 0.216 **
<0.0001
Total cholesterol (mmol/L) 0.027 0.653 0.081 0.176 0.196 *
0.0001
Triglyceride (mmol/L) 0.172** 0.004 0.087 0.141 0.123* 0.038
HDL-C (mmol/L) −0.091 0.124 −0.023 0.699 −0.064 0.285
LDL-C (mmol/L) 0.047 0.429 0.082 0.170 0.209 **
<0.0001
ALT (IU/L) 0.590 **
<0.0001 0.507 **
<0.0001
AST (IU/L) 0.590 **
<0.0001 0.366 **
<0.0001
GGT (IU/L) 0.507** <0.0001 0.366** <0.0001

Pearson correlation coefficient with corresponding p-value (p < 0.05 is considered a significant). ** Corre-
lation is significant at the 0.01 level (2-tailed). * Correlation is significant at the 0.05 level (2-tailed). BMI,
body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; FBG, fasting blood glucose;
TC, total cholesterol; TG, triglyceride; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density
lipoprotein cholesterol; ALT, alanine aminotransferase; AST, aspartate aminotransferase; GGT, gam-
ma-glutamyltransferase.

Table 3. Pearson correlation using ALT, AST and GGT as dependent variables in the
combined groups studied after Age and BMI adjustment as a covariance.

N = 284 ALT AST GGT

r P-value r P-value r P-value
Sex (M/F) 0.116 0.051 0.114 0.055 0.017 0.772
SBP (mmHg) −0.018 0.764 −0.053 0.377 0.124* 0.038
DBP (mmHg) 0.024 0.686 −0.078 0.194 0.213** 0<0.0001
FBG (mmol/L) 0.161 0.007 −0.074 0.213 0.213 **
<0.0001
Total cholesterol (mmol/L) 0.027 0.652 0.085 0.155 0.199 0.001
Triglyceride (mmol/L) 0.171 0.004 0.090 0.130 0.127 0.033
HDL-C (mmol/L) −0.104 0.081 −0.026 0.668 −0.056 0.351
LDL-C (mmol/L) 0.052 0.388 0.087 0.147 0.208 <0.0001
ALT (IU/L) 0.589 **
<0.0001 0.514 **
<0.0001
AST (IU/L) 0.589 **
<0.0001 0.368 **
<0.0001
GGT (IU/L) 0.514** <0.0001 0.368** <0.0001

Pearson correlation coefficient with corresponding p-value (p < 0.05 is significant). ** Correlation is signif-
icant at the 0.01 level (2-tailed). * Correlation is significant at the 0.05 level (2-tailed). BMI, body mass in-
dex; SBP, systolic blood pressure; DBP, diastolic blood pressure; FBG, fasting blood glucose; HDL-C,
high-density lipoprotein cholesterol; LDL-cholesterol, low-density lipoprotein cholesterol; ALT, alanine
aminotransferase; AST, aspartate aminotransferase; GGT, gamma-glutamyltransferase.

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 L. S. Bin Dahman et al.

4. Discussion
Despite the incidence of diabetes is increasing worldwide and its prevalence is
higher in developing countries, no studies have examined the relationship be-
tween elevated liver enzymes and T2D risk in Yemeni patients. Our study,
therefore, was focused on the liver as the vital organ contributing to glucose ho-
meostasis during fasting and postprandial stage. Serum ALT, AST, and GGT
were taken from each participant and used for this work. Additionally, most
people aged ≥ 45 years in developing countries suffer from diabetes [19]. These
findings were convenient with our study showed that T2D patients had signifi-
cantly higher mean age compared to healthy control subjects (Table 1).
Besides, our present findings also observed significantly increased BMI, sys-
tolic BP, and diastolic BP in T2D patients than healthy control subjects. Besides,
the present study also showed that serum FBG, total cholesterol, and LDL-C
were significantly higher in T2D patients than healthy control subjects, while, no
significant difference was found among both groups for serum triglyceride. In
contrast, HDL-C was significantly lower in T2D patients. Our study further re-
vealed higher levels of GGT in T2D patients. While AST was significantly lower
in T2D patients. Besides, no significant difference was found among both groups
for ALT. Such a positive relationship between liver enzymes and blood lipids
profile in T2D patients has been observed in previous studies [2] [20] [21] [22]
[23].
This finding supports the role of hepatic insulin resistance in the pathogenesis
of NAFLD in patients with T2D [24] [25]. Moreover, Cho et al. reported a cor-
relation between ALT activity and increased fatty liver [26]. The impairment of
the normal process of synthesis and elimination of triglycerides may progress to
fibrosis, cirrhosis, and hepatocellular carcinoma [27] [28].
In addition to its effect on lipid metabolism, insulin also contributes a proin-
flammatory effect to liver abrasion [12]. Thus, inflammation contributes to IR.
Pro-inflammatory cytokines and transcription factors are highly expressed in
white adipose tissue and liver. Obesity, which is a state of chronic low-grade in-
flammation and a risk factor for IR and NAFLD, is induced by the overnutrition
and is a primary cause of decreased insulin sensitivity. Obesity leads to lipid ac-
cumulation and activates the c-Jun N-terminal kinase (JNK) and nuclear fac-
tor-kappa B (NF-κB) signaling pathways, which consequently increase the pro-
duction of pro-inflammatory cytokines, such as tumor necrosis factor-alpha
(TNF-α) and interleukin-6 (IL-6) [29]. Besides, various adipose tissue-derived
proteins, such as adiponectin and leptin, are considered to be major links be-
tween obesity, IR, and related inflammatory disorders [30].
GGT is known as a marker of hepatobiliary disorders and is associated with
other pathological conditions like diabetes. Free radicals generated by diabetes
consume glutathione which induces the increased expression of GGT in hepato-
cytes. Various studies have suggested the association of GGT concentrations
with T2D [31] [32] [33] [34], and hyperlipidemia [35]. These findings are in

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L. S. Bin Dahman et al.

agreement with our study; GGT was significantly associated with the hypergly-
cemic and hyperlipidemia profile. We observed ALT and GGT together were
positively correlated. Moreover, some data also reported elevated GGT levels
with ALT in T2D patients with dyslipidemia [32] [33] [36]. Although we did not
confirm the presence of fatty liver by ultrasound techniques, we showed the rela-
tionship of ALT, AST, and GGT with the predictors of diabetes and lipid profile
parameters, presenting hepatocellular injury.
A study of male Korean workers found that AST was independently associated
with diabetes [37], while in a study of male Japanese office workers AST was not
associated with T2D risk [33]. Some studies also reported that ALT is a signifi-
cant predictor of diabetes while AST is not [38]. These findings are in agreement
with our findings as AST does not show considerable relationship with the stu-
died parameters. Besides, Clark et al. also suggested that mild or chronic eleva-
tions of these aminotransferases may be due to NAFLD [39] [40].
The strength of the present study included adjustment for well-established
diabetes risk factors including BMI, blood lipids, and hypertension. However,
there are some limitations. First, our sample size may be small and thus under-
powered to detect the interaction with ALT and GGT. Second, we measured liv-
er enzymes only once and may not represent a long-term profile. Third, we did
not measure hepatitis B and C infection, which could result in elevated liver en-
zymes. Fourth, we did not measure insulin, CRP, leptin, and, adiponectin as the
predictive biomarkers links between obesity, hepatic IR, and related inflamma-
tory disorders in T2D patients. Thus, a further large sample size with measure-
ment of insulin, CRP, leptin, adiponectin, and interleukins are required to con-
firm these correlations. We conclude that higher levels of ALT and GGT are
used as the predictive biomarkers for NAFLD in T2D patients with hyperlipide-
mia.

5. Conclusion
Higher levels of ALT and GGT may be used as the predictive markers for NAFLD
in T2D patients with hyperlipidemia. Thus, routine screening of liver enzymes
and lipid profile in T2D patients is recommended for the early detection of liver
abnormalities and diminish diabetes complications.

Acknowledgements
The authors are grateful to Al-Huda Medical Agency, Mukalla, Yemen, for fund-
ing the study and the Ibn-Sina Hospital, Mukalla, Yemen for technical support.
Also, we are thankful to the physicians and nurses who recruited and collected
the data of the participants. Special thanks to National Center for the Public
Health Laboratories, Mukalla for biochemical analysis. Special thanks to Stu-
dents of Medical Laboratory Sciences Department (Ali Alqaaiti, Saleh Daiban,
Sabri Barafah, Afaf Aldibani, Safa Basawaid, Noor Zahfan and Nasser Al-Mohamdi)
for the performance of data and sample collection, data entry, and biochemical

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 L. S. Bin Dahman et al.

investigations. Special thanks to Ms. Nasiba Al-Aidros for the statistical analysis.

Conflicts of Interest
The authors declare no conflicts of interest regarding the publication of this pa-
per.

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