Impact of Zinc to Copper Ratio and Lipocalin 2 in Obese Patients Undergoing Sleeve Gastrectomy.
Conditions: Nutritional Disorder
Sponsor: Alexandria University

 
 
 
 
Impact of Zinc to Copper ratio and Lipocalin -2  
in Obese Patients Undergoing Sleeve Gastrectomy.
 
 
 
 
 
 
Serial no: 0304707 
 
 
 
9/13/2020 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
 
Impact of Zinc to Copper ratio and Lipocalin -2  
in Obese Patients Undergoing Sleeve Gastrectomy.
 
 
                                   Hala Mourad Demerdash1, Ahmed A Sabry2, Omar E Arida1 
Department of Clinical Pathology Alexandria University Hospitals; Department of Surgery 
Alexandria University Faculty of Medicine. 
 
     Obesity represents tremendous threat to health globally. WHO conveyed that over 10% of 
the world’s population were classified as obese in 2016, which signifies 3-fold increase in 
frequency of obesity since 1975. Laparoscopic Sleeve Gastrectomy (LSG) has proved to be an 
effective procedure for achieving considerable weight loss with significant improvement in 
obesity-related comorbidities.  
    
      A possible role of trace elements in the pathogenesis of obesity has been largely ignored. In 
particular zinc (Zn) and Copper (Cu) are crucial TE, that act as structural ions in hormones, 
proteins and receptors and cofactors in various enzymatic reactions. It has been theorized that 
balance between Zn and Cu has an influence on antioxidant mechanisms and development of 
associated comorbidities. Nevertheless, few studies have systematically evaluated TE in 
morbidly obese patients undergoing bariatric surgery. 
 
    Lipocalin 2 (Lcn2), also known as NGAL (neutrophil gelatinase-associated lipocalin), Lcn2 is 
adipokine that belongs to lipocalin family. It is a 25- KD α-glycoprotein originally identified in 
human neutrophils. Lcn2 overexpression in adipose tissue stimulates the production of pro-
inflammatory cytokine as interleukin 6 (IL-6) and receptor activator of NF-kB ligand.  
 
    The aim of the current study primarily was to investigate the value of zinc to copper ratio as 
possible biomarker of TE imbalance in morbidly obese subjects undergoing LSG. Secondly to 
correlate it with lipocalin 2 (Lcn2) with respect to Anthropometric measurements and other 
metabolic markers prospectively.  
 
Study design 
 
CONSORT 2010 Flow Diagram 
 
Assessed for eligibility (n= 120 ) 
Enrollment 

 
Materials and methods: 
Recruitment  
Morbidly obese subjects attending clinic at Surgery department for laparoscopic sleeve 
gastrectomy Alexandria University Hospitals.  
   Pre-assignment Details  
adult morbidly obese subjects were included age above 20 years, BMI above 40  
Suffering from comorbidities as hypertension, DM, dyslipidemia. 
Assigned participants were clinically evaluated for comorbidities as hypertension, DM, 
dyslipidemia. 
As well as signs of nutritional deficiency as anemia, brittle nails.  
 
 
Group Information   
one  group of participants eligible for laparoscopic sleeve gastrectomy were assigned according 
to their will to participate in study.  
Period of evaluation: 
First visit: preoperative for clinical assessment of participants, determine BMI and waist 
circumference and withdrawal of serum blood sample 
Second visit: within one month after surgery to make sure that no complication occurred after 
surgery. 
Third visit: nine months postoperative for revaluation of participants, determine BMI and waist 
circumference, and withdrawal of a serum blood sample 
 
Number of participants at initiating the period of study. 
They were 120 morbidly obese subjects. 
Number of participants at the end of the period of study. 
They were 107 subjects, 13 obese subject withdraw from study as they didn’t come during 
follow up period after 9 months. 
 
Participants according Sex (69 females, and 38 male), with the mean age of 41.6±8.9 years. The 
mean preoperative BMI was 47.43±5.4 kg/m2. Then, they were evaluated 9 months after LSG. 
 
Preoperative and Postoperative Clinical characteristics and metabolic variables in studied 
subjects. 
 
 
Preoperative 
9 months postoperative 
P 
Body weight (Kg) 
129.7 ± 12.1 
93.4 ±13.6 
0.0013* 
BMI (kg/m2) 
47.43±5.4 
35.7±3.8 
0.0052* 
Waist circumference 
(cm) 
130.00 ± 4.68 
91.82 ± 3.73 
0.001* 

Systolic BP (mmHg) 
146.0±17.0 
132.0±11.0 
0.001* 
Total cholesterol 
(mmol/L) 
5.85 ± 0.41 
4.64 ± 0.31 
0.035* 
Triglycerides 
(mmol/L) 
2.20 ± 0.23 
1.92 ± 0.24 
0.106 
HDL cholesterol 
(mmol/L) 
1.23 ± 0.19 
1.39 ± 0.2 
0.041* 
LDL cholesterol 
(mmol/L) 
3.37 ± 0.23 
2.97 ± 0.21 
0.022* 
HOMA-IR 
2.64 ± 1.3 
1.44 ± 0.81 
0.013* 
 S. Leptin (ng/ml) 
102.87 ± 49.16 
33.47 ±12.76 
0.0001* 
CRP (mg/L) 
8.4±5.91 
3.2±2.98 
0.001* 
Lipocalin 2 (µg/L) 
107.24±36.8 
51.6±12.73 
0.001* 
Albumin (g/dl) 
4.05±0.21 
 
3.91±0.29 
0.113 
 
*Statistically significant at (p≤0.05). 
 
 
Outcome measures: 
primarily was to investigate the value of zinc to copper ratio as possible biomarker of TE 
imbalance in morbidly obese subjects undergoing LSG.  
For detection of presence of micronutrient deficiency in morbid obesity in form of zinc to 
copper ratio and re-evaluate it after loss of weight 
 
Secondly to correlate it with lipocalin 2 (Lcn2) with respect to Anthropometric measurements 
and other metabolic markers prospectively.  
As zinc to copper ratio is considered as biomarker of micronutrient status; therefore, correlate 
it with other biomarkers of inflammation (lipocalin 2) and other parameters as BMI, FBG to 
determine if micronutrient status improve after weight loss or not 
Time frame:  9 months. 
 
Follow-up and outcome parameters: 
    All studied subjects will be followed up for early postoperative complications (within the first 
month) as Bleeding or Leak. Then they will be reviewed after 9 months postoperatively for 
assessment of anthropometric measurements, control of preoperative comorbidities, and 
manifestations of TE deficiencies (anemia, hair loss, teeth problems, edema. etc.). 

 
 
Anthropometric parameters 
 
Body mass index (BMI) and waist circumference will be measured preoperative and 9 months 
postoperative. 
 
Biochemical parameters 
 
   Fasting blood samples will be collected from participants prior to surgery and nine months 
postoperative, after overnight fast and divided into two tubes; EDTA for complete blood count, 
the rest into plastic tubes and serum sample.  
  Serum glucose and Total cholesterol, HDL- cholesterol, LDL- cholesterol, and triglyceride, total 
protein and Albumin. Serum iron (Fe), and ferritin. 
   Serum insulin, Ceruloplasmin, Zn and Cu levels, CRP and lipocalin-2 (Lcn2) . 
 
 
Statistical analysis 
     
    All data will be analyzed with Statistical Package for the Social Sciences version 20 software 
(SPSS, Inc., Chicago, IL). Results will be displayed as mean ± SD. Paired Student’s t-test used to 
compare the data pre-operative and nine months postoperative. The chi-squared test used for 
category variables. Spearman correlation coefficient used to detect the correlation between 
different variables. Statistical correlations calculated by Pearson’s correlation test. P < 0.05 is 
considered significant.  
 
 
 
Dr Hala Demerdash  
Consultant Clinical Pathology at Alexandria University Hospitals 
Alexandria University, Faculty of Medicine Alexandria University Hospitals  
Mobile Telephone: +01229501257 
Faculty contact no: +201287740750 
Email: demerdashh@yahoo.com