|Year : 2018 | Volume
| Issue : 3 | Page : 97-102
The abnormal iron homeostasis among Egyptian obese children and adolescents: relation to inflammation of obesity
Ehab K Emam1, Marwa H.A Hamed1, Dina A Fouad2, Reham O Abd-Allah3
1 Department of Paediatric, Clinical Nutrition Unit, Faculty of Medicine, Ain Shams University, Cairo, Egypt
2 Department of Clinical Pathology (Hematology), Faculty of Medicine, Ain Shams University, Cairo, Egypt
3 General Practioner in ER, New Cairo Hospital, Cairo, Egypt
|Date of Submission||11-Nov-2017|
|Date of Acceptance||02-Jan-2018|
|Date of Web Publication||3-Dec-2018|
Marwa H.A Hamed
Department of Pediatrics, Clinical Nutrition Unit, Faculty of Medicine, Ain Shams University, Cairo 1159
Source of Support: None, Conflict of Interest: None
Background Obesity is associated with low-grade inflammatory changes that increase Fe tissue storage and affect the level of circulating serum Fe, leading to tissue overload and decreased availability of Fe for hematopoiesis.
Objectives The objectives of this study were to determine the relation between the low iron state and the chronic inflammation found in obese children and to assess the role of inflammatory markers in the detection of iron status.
Design and setting This was a case–control study. This study was conducted in the outpatient and clinical nutrition clinics of Pediatric Hospital, Ain Shams University.
Patients and methods This was a case–control study conducted on 50 obese children and adolescents over 1 year. They were divided into two subgroups: iron deficient and noniron deficient patients. The study also included 20 normal weight children and adolescents as controls. All patients were subjected to the obesity sheet, anthropometric measurements, complete blood picture, measurement of iron profile and high-sensitivity C-reactive protein (hs-CRP).
Results There were significantly lower mean values of hemoglobin, serum iron, ferritin and transferrin saturation among obese than among nonobese children. The mean serum level of hs-CRP was significantly higher among obese children than controls, and, of the 50 obese patients, 62% had high levels. The mean serum level of hs-CRP among anemic obese patients was significantly higher than in the nonanemic obese group. The hs-CRP showed significant positive correlations with BMI and significant negative correlations with serum iron.
Conclusion The chronic inflammation changes of obesity lead to a low iron state. Thus, regular follow-up of obese children by measuring serum hs-CRP, hemoglobin, and iron profile is mandatory.
Keywords: high-sensitivity C-reactive protein, inflammation, iron, obesity
|How to cite this article:|
Emam EK, Hamed MH, Fouad DA, Abd-Allah RO. The abnormal iron homeostasis among Egyptian obese children and adolescents: relation to inflammation of obesity. Egypt J Haematol 2018;43:97-102
|How to cite this URL:|
Emam EK, Hamed MH, Fouad DA, Abd-Allah RO. The abnormal iron homeostasis among Egyptian obese children and adolescents: relation to inflammation of obesity. Egypt J Haematol [serial online] 2018 [cited 2019 Apr 18];43:97-102. Available from: http://www.ehj.eg.net/text.asp?2018/43/3/97/246780
| Introduction|| |
Obesity is a worldwide chronic public health problem . There is great evidence that the initiating events in obesity-induced inflammation start early in childhood and lead to elevated inflammatory markers such as high-sensitivity C-reactive protein (hs-CRP) ,.
It was found that obesity is associated with iron deficiency and iron profile abnormalities, which appear to be caused by several factors such as decreased intake, insufficient bioavailability, and deficient intestinal iron uptake as well as iron release from stores because of an overexpression of hepcidin ,.
Adiposity-related inflammation is associated with a reduction in the normal upregulation of iron absorption in iron-deficient obese individuals, and this adverse effect may be ameliorated by fat loss .
It is important to identify the probable cause of the iron deficiency in obese children because of increased susceptibility of this age group to the negative effects of iron deficiency .
| Aims|| |
The aims of this study were the evaluation of the relation between the low iron state and the chronic inflammation found in obese children and to assess the role of inflammatory markers in the detection of iron status.
| Patients and methods|| |
This is a case–control study conducted on 50 [34 male and 16 female obese children and adolescents (>95th BMI percentiles)] obese children and adolescents diagnosed according to the criteria of Baker et al. . They were recruited from outpatient and clinical nutrition clinics of Pediatric Hospital, Ain Shams University. Their ages ranged between 2 and 15 years with a mean age of 10.12±3.24 years.
We excluded from the study, patients with an identified risk for iron deficiency or red cell disorder as those with heavy menstruation, gastrointestinal bleeding, elevated levels of lead, chronic anemias such as thalassemia, sickle cell disease, sidroblastic or aplastic anemia, those on a vegan diet and patients with cancer or inflammatory disorders such as inflammatory bowel disease, autoimmune or collagen disorders, patients with secondary obesity or endocrinal disorders as well as patients who were receiving iron supplements, immunosuppressive medications or corticosteroids within the last year.
The included patients (group I) were divided according to their iron profile  into two subgroups: group Ia, which included 21 male participants and nine female participants who were iron deficient, and group Ib, which included 13 male participants and seven female participants who were noniron deficient patients.
The study also included 20 controls (group II) (13 male participants and seven female participants) who were children and adolescents with normal weight (15th <85th BMI percentiles). Their ages ranged between 2 and 15 years with a mean age of 9.88±3.44 years.
The sample size was calculated to provide 95% confidence and 80% power in statistical analysis.
The Ethical and Research Committee of the Council of Children Department, Ain Shams University, Egypt, approved this study proposal. Full description of what was required in the study was discussed with the parents of the participants, and consent was obtained before the evaluation.
| Methods|| |
The enrolled patients were subjected to the obesity sheet aiming to reveal the demographic data, obesity risk factors, demonstration of morbidities and comorbidities of obesity, body image, psychological problems and previous history of diet control.
Anthropometric measurements were performed to all involved children and adolescents using standardized equipments, and we followed the recommendations of the International Biological Programme . These measurements included weight (wt) in kilograms (kg), height (ht) in centimeter (cm), waist circumference (WC) in centimeter (cm), mid-upper arm circumference (MUC) in centimeter (cm) and triceps and subscapular skinfold thickness in millimeter (mm) using Harpenden skinfold caliper (England Baty International Victoria Road Burgess Hill West Sussex RHI5 9LR). BMI was calculated according to the following equation: BMI=weight (kg)/height (m2) .
Age-specific and sex-specific z scores for height, weight, and BMI were calculated by using year 2000 growth data from the National Center for Health Statistics, and Centers for Disease Control and Prevention. This was achieved through using the Window-based software Epi Info. Children were classified by BMI z score categories as normal weight (BMI z score >−2 SD<+1 SD), overweight (BMI z score ≥+1 SD<+2 SD), and obese (BMI z score≥+2 SD) .
A volume of 6 ml peripheral blood was collected from all participants using standard venipuncture techniques in two tubes. Of which 2 ml on EDTA was utilized for complete blood picture, and 4 ml serum was utilized for iron profile and hs-CRP. Hemolytic, lipemic, or turbid samples were excluded after centrifugation.
Hemoglobin concentration was measured using Coulter counter Max-M (Coulter Corporation, Florida, USA) to assess for anemia, with cut-off values based on the fifth percentile for a reference group .
Iron profile assessment
Serum levels of iron were measured by colorimetric reaction kits (supplied by Beckman Coulter, Brea, California, USA) on an automated analyzer (CX7, Synchron Clinical System; Beckman Coulter). Reference value in children for serum iron is 50–120 μg/dl.
Serum ferritin was assessed by IMMULITE/IMMULITE 1000 Ferritin analyzer (Siemens, Los Angeles, California, USA). Reference value in children for serum ferritin is greater than 10 ng/dl.
Total iron-binding capacity (TIBC) was measured by colorimetric kits produced by Spectrum Company (München, Germany). Reference value in children for TIBC is 250–400 μg/dl.
Transferrin saturation was calculated by using the following equation: saturation of Tf=(serum iron divided by TIBC)×100 .
The child was considered as iron deficient if serum iron was lower than 50 μg/dl, serum TIBC was higher than 400 μg/dl , serum ferritin was less than 10 ng/ml , or transferrin saturation was less than 16% .
Hs-CRP was used as a marker of inflammation. Serum levels of hs-CRP were measured using ELISA . The hs-CRP values were classified by American Heart Association standards for risk for cardiovascular disease as low (<1 mg/l), intermediate (1–3 mg/l), or high (>3 mg/l) .
The collected data were revised, coded, tabulated, and introduced into a PC using statistical package for the social sciences (SPSS Inc., Chicago, Illinois, USA) .
| Results|| |
The results of this work show that of the 50 obese patients, 27 (54%) had a family history of obesity, 15 (30%) had a habit of consuming fast food, 35 (70%) patients bought food from street vendors, 46 (92%) were heavy beverage consumers, 25 (50%) patients had their food while watching TV, 29 (58%) patients had negative nutritional behavior, 41 (82%) did not follow any diet previously, and 42 (84%) did not have physical exercise.
There were significantly lower mean values of hemoglobin level, serum iron, serum ferritin, and transferrin saturation and significantly higher mean serum TIBC among obese patients (P<0.001) ([Table 1]).
|Table 1 Comparison between obese and nonobese patents with regard to blood picture and iron profile|
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On comparing between anemic and nonanemic obese cases, we found that the percentages of patients belonging to the low socioeconomic class were significantly higher among anemic (76%) than nonanemic patients (10%) with P value of less than 0.05. Further, the percentages of negative feeding behavior and the absence of exercise practice were significantly higher among anemic (90 and 93.3%) than in nonanemic obese cases, with P value of less than 0.01 and 0.05, respectively. However, there were no significant differences as regards other personal and familial characteristics, other nutritional habits, previous diet, mineral intake, or anthropometric measurements.
The mean serum level of hs-CRP was significantly higher in the obese group than in the nonobese group with P value of less than 0.001 ([Table 2]).
Moreover, the mean serum level of hs-CRP among anemic obese patients (mean±SD, 8.35±2.97) was significantly higher than in the nonanemic obese group (3.16±1.89 with P<0.001] ([Table 3]).
|Table 3 Comparison between anemic and nonanemic obese cases as regards high-sensitivity C-reactive protein|
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The hs-CRP proved to have significant positive correlations with mean z scores of weight, BMI ([Figure 1]), and triceps skinfold and with TIBC and significant negative correlations with hemoglobin, serum iron ([Figure 2]), serum ferritin, and transferrin saturation ([Table 4]).
|Figure 1 Scattered diagram showing a positive correlation between high-sensitivity C-reactive protein and BMI. Hs-CRP, high-sensitivity C-reactive protein.|
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|Figure 2 Scattered diagram showing a negative correlation between high-sensitivity C-reactive protein and serum iron. Hs-CRP, high-sensitivity C-reactive protein.|
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|Table 4 Correlations between high-sensitivity C-reactive protein and anthropometric measurements, hemoglobin concentration, and serum levels of iron profile|
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The mean z scores of BMI showed significant negative correlations with serum iron, serum ferritin, and transferrin saturation and a significant positive correlation with TIBC. However, no significant correlation was found between mean z scores of BMI and hemoglobin levels ([Table 5]).
| Discussion|| |
In the present study, it was evident that the mean serum level of hs-CRP was significantly higher in the obese than in the nonobese group, and the majority of the studied obese children had levels of hs-CRP that indicated high or intermediate risk for cardiovascular disease. This result is in agreement with the study published by Pearson et al. , whereas the majority of the studied nonobese controls had levels of hs-CRP that indicated low or intermediate risk for cardiovascular diseases. Further, we proved a positive correlation between BMI and hs-CRP among obese patients. These results are in accordance with the study of Baker et al.  who showed that an elevated BMI in childhood was associated with significantly increased risk of both fatal and nonfatal coronary heart disease later in life. Further, the study of Diaz et al.  confirmed that obese children had elevated levels of hs-CRP and that the more obese a child was, the more the systemic inflammation is the child was exposed to. This is explained by the fact that excess fat deposited in visceral organs leads to low-grade chronic inflammation that causes insulin resistance and the associated comorbidities of metabolic syndrome Halberg et al. .
In this study, obese cases recorded significantly lower values of hemoglobin, serum levels of iron and ferritin, transferrin saturation and significantly higher values of TIBC compared with nonobese controls. Further, BMI revealed significant negative correlations with serum levels of iron and ferritin and with transferrin saturation and a significant positive correlation with TIBC. This is in agreement with the studies of Cepeda-Lopez et al.  and Moschonis et al.  whose results suggested that increasing BMI was associated with lower serum levels of iron and transferrin saturation. Moreover, Azab et al. , Abd-El Wahed et al. , and Shekarriz and Vaziri , found that serum levels of iron and ferritin were significantly lower among obese children compared with nonobese Egyptian children. Moreover, in a cross-sectional study in Chilean women, obese women had lower fractional iron absorption than did overweight and normal weight women (P<0.05) .
In contrast to our study, Tussing-Humphreys et al.  and Cheng et al.  found hemoglobin levels to be higher in obese individuals, and Tussing-Humphreys et al.  found the ferritin levels to be higher in the obese children, even before iron supplementation. Moreover, Baumgartner et al.  stated that, although iron deficiency was found in overweight and obese individuals, ferritin was usually normal or increased. Ausk and Ioannou  hypothesized that serum ferritin (acute-phase reactant) may increase in obesity because of inflammation; moreover, it would be expected to cause a decrease in serum iron, a well-documented response to infection or inflammation. Therefore, their findings suggested that obesity was associated with changes in serum iron markers that are typical of chronic inflammation, but was not actually associated with anemia of inflammation.
The high rate of iron deficiency among obese children is explained by several mechanisms, such as consumption of high calories, poor dietary iron intake, and sedentary life style, resulting in decreased breakdown of myoglobin and increased iron requirements for increased red cell mass . A more likely explanation is that chronic adiposity-related inflammation causes decreases in intestinal iron absorption and/or increases reticuloendothelial iron sequestration, which is caused by increased hepcidin concentrations . Hepcidin is produced primarily in the liver but is expressed in adipose tissue as well . Interleukin-6 increases its expression, which is higher in obese children. In addition, there are data to suggest that the adipose-derived hormone, leptin, increase hepcidin expression . Hepcidin is an important regulator of Fe homeostasis, inhibiting Fe absorption at the enterocyte and sequestering Fe at the macrophage, which could lead to decreased Fe stores and hypoferremia and anemia of chronic disease observed in obesity . It was suggested that inflammation-induced hepcidin was likely causing a decrease in dietary iron absorption, by diminishing the expression of ferroprotein (Fpn) located on the basolateral membrane of intestinal enterocytes, thus impairing dietary repletion efforts .
In our study, the mean serum level of hs-CRP among anemic obese patients was significantly higher than in the nonanemic obese group, and, of the 30 anemic obese patients, 29 (98%) had high levels and only one (2%) had intermediate levels of hs-CRP. Further, we found negative correlations between hs-CRP levels and the serum levels of iron, ferritin and transferrin saturation. This is in accordance with Yanoff et al.  whose data supported that it is the inflammation of obesity that negatively influences iron homeostasis and with Richardson et al.  whose study showed negative associations of hs-CRP with serum iron, transferrin saturation, and hemoglobin. Moreover, Anty et al.  reported on obese adult women who had bariatric surgery, and found that the postoperative decrease in BMI was associated with decrease in CRP levels, with an associated improvement in markers of iron status, further suggesting that it is obesity that leads to inflammation, which in turn contributes to abnormal measures of iron homeostasis.
Finally, we concluded that the chronic inflammation of obesity disturbs the basic iron homeostasis in obese children and adolescents and leads to a low iron profile among obese people. Thus, regular follow-up of obese children and adolescents by measuring serum hs-CRP, hemoglobin, serum iron, ferritin, transferrin concentration, and TIBC is mandatory to offer proper treatment when needed.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Pinhas-Hamiel O, Newfield RS, Koren I, Agmon A, Lilos P, Phillip M. Greater prevalence of iron deficiency in overweight and obese children and adolescents. Int J Obes
Singer K, Lumeng CN. Initiation of metabolic inflammation in childhood obesity. J Clin Invest
Guran O, Akalin F, Ayabakan C, Dereli FY, Haklar G. High-sensitivity C-reactive protein in children at risk for coronary artery disease. Acta Paediatrica
Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med
Brotanek JM, Gosz J, Weitzman M, Flores G. Iron deficiency in early childhood in the United States: risk factors and racial/ethnic disparities. Pediatrics
Cepeda-Lopez AC, Allende-Labastida J, Melse-Boonstra A, Osendarp SJ, Herter-Aeberli I, Moretti D et al.
The effects of fat loss after bariatric surgery on inflammation, serum hepcidin, and iron absorption: a prospective 6-mo iron stable isotope study. Am J Clin Nutr
Halterman JS, Kaczorowski JM, Aligne CA, Auinger P, Szilagyi PG. Iron deficiency and cognitive achievement among school-aged children and adolescents in the United States. Pediatrics
Baker S, Barlow S, Cochran S. Overweight children and adolescents: a clinical report of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr
Burtis CA, Edward RA. Principles of colorimetric determination of unsaturated iron binding capacity in serum. In: Burtis CA, Edward RA, David EB, editors. Tietz textbook of clincal chemistry
4th ed. Philadelphia: Elsevier Saunders; 2004. 2195–2197.
Hiernaux J, Tanner JM. Growth and physical studies. In: Weiner JS, Lourie SA, editors. Human biology: a guide to field methods
. London: IBP; Oxford, UK: Blackwell Scientific Publications; 1969. 621–622.
Deurenberg P, Weststrate JA, Seidell JC. Body mass index as a measure of body fatness: age- and sex-specific prediction formulas. Br J Nutr
Ogden CL, Flegal KM, Carroll MD, Johnson CL. Prevalence and trends in overweight among US children and adolescents, 1999–2000. JAMA
Looker AC, Dallman PR, Carroll MD, Gunter EW, Johnson CL. Prevalence of iron deficiency in the United States. J Am Med Assoc
Kasvosve I, Delanghe J. Total iron binding capacity and transferrin concentration in the assessment of iron status. Clin Chem Lab Med
McPherson RA, Pincus MR. Iron deficiency anemia: diagnosis and management. In: McPherson RA, Pincus MR, editors. Henry’s clinical diagnosis and management laboratory methods
. 21st ed. Philadelphia, Pennsylvania: WB Saunders; 2007. 455–482
WHO. Iron deficiency: assessment, prevention, and control. A guide for programme managers
. Geneva: World Health Organization; 2001.
Uotila M, Ruoslahti E, Engvall E. Two-site sandwich enzyme immunoassay with monoclonal antibodies to human alpha-fetoprotein. J Immunol Methods
Pearson TA, Mensah GA, Alexander RW, Alexander RW, Anderson JL, Cannon RO 3rd et al.
Centers for Disease Control and Prevention; American Heart Association. Markers of inflammation and cardiovascular disease: application to clinical and public health practice. A statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation
Chicago IL. SPSS 15.0. 1 for windows
Baker JL, Olsen LW, Sorensen TIA. Childhood body-mass index and the risk of coronary heart disease in adulthood. N Engl J Med
Diaz JJ, Arguelles J, Malaga I, Perillan C, Dieguez A, Vijande M, Malaga S. C-reactive protein is elevated in the offspring of parents with essential hypertension. Arch Dis Child
Halberg N, Wernstedt I, Scherer PE. The adipocyte as an endocrine cell. Endocrinol metab Clin North Am
Cepeda-Lopez AC, Osendarp SJM, Melse-Boonstra A, Aeberli I, Gonzalez-Salazar F, Feskens E. Sharply higher rates of iron deficiency in obese Mexican women and children are predicted by obesity-related inflammation rather than by differences in dietary iron intake. Am J Clin Nutr
Moschonis G, Chrousos GP, Lionis C, Mougios V, Manios Y, Healthy Growth Study Group. Association of total body and visceral fat mass with iron deficiency in preadolescents. Br J Nutr
Azab SFA, Saleh SH, Elsaeed WF, Elshafie MA, Sherief LM, Esh AMH. Serum trace elements in obese Egyptian children: a case-control study. Ital J Pediatr
Abd-El Wahed MA, Mohamed MH, Ibrahim SS, El-Naggar WA. Iron profile and dietary pattern of primary school obese Egyptian children. J Egypt Public Health Assoc
Shekarriz R, Vaziri MM. Iron profile and inflammatory status of overweight and obese women in Sari, North of Iran. Int J Hematol Oncol Stem Cell Res
Mujica-Coopman MF, Brito A, Lolez de Romana D, Pizarro F, Olivares M. Body mass index, iron absorption and iron status in childbearing age women. J Trace Elem Med Biol
Tussing-Humphreys LM, Liang H, Nemeth E, Freels S, Braunschweig CA. Excess adiposity, inflammation, and iron-deficiency in female adolescents. J Am Diet Assoc
Cheng HL, Bryant C, O’Connor H, Rooney K, Steinbeck K. The relationship between obesity and hypoferraemia in adults: a systematic review. Obes Rev
Tussing-Humphreys LM, Nemeth E, Fantuzzi G, Freels S, Guzman G, Holterman AX, Braunschweig C. Elevated systemic hepcidin and iron depletion in obese premenopausal females. Obesity (Silver Spring)
Baumgartner J, Smuts CM, Aeberli I, Malan L, Tjalsma H, Zimmermann MB. Overweight impairs efficacy of iron supplementation in iron-deficient South African children: a randomized controlled intervention. Int J Obes
Ausk KJ, Ioannou GN. Is obesity associated with anemia of chronic disease? A population −based Studty. Obesity (Silver Spring)
Yanoff JB, Menzie CM, Denkinger B, McHugh T, Remaley AT, Yanovski JA. Inflammation and iron deficiency in the hypoferremia of obesity. Int J Obes (Lond)
Zimmermann MB, Zeder C, Muthayya S, Winichagoon P, Chaouki N, Aeberli I et al.
Adiposity in women and children from transition countries predicts decreased iron absorption, iron deficiency and a reduced response to iron fortification. Int J Obes (Lond)
Bekri S, Gual P, Anty R, Luciani N, Dahman M, Ramesh B et al.
Increased adipose tissue expression of hepcidin in severe obesity is independent from diabetes and NASH. Gastroenterology
Chung B, Matak P, McKie AT, Sharp P. Leptin increases the expression of the iron regulatory hormone hepcidin in HuH7 human hepatoma cells. J Nutr.
Del Giudice EM, Santoro N, Amato A, Brienza C, Calabrd P, Wiegerincket ET et al.
Hepcidin in obese children as a potential mediator of the association between obesity and iron deficiency. J Clin Endocrinol Metab
Humphreys LT, Pustacioglu C, Nemeth C, Braunschweig C. Rethinking iron regulation and assessment in iron deficiency, anemia of chronic disease, and obesity: introducing hepcidin. J Acad Nutr Diet
Richardson MW, Ang L, Visintainer PF, Wittcopp CA. The abnormal measures of iron homeostasis in pediatric obesity are associated with the inflammation of obesity. Int J Pediat Endocrinol
:713269. PMID: 19956746; PMCID: PMC2775635
Anty R, Dahman M, Iannelli A, Gual P, Staccini-MYX A, Amor IB et al.
Bariatric surgery can correct iron depletion in morbidly obese women: a link with chronic inflammation. Obes Surg
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]