Study of Serum Hepcidin as a Potential Mediator of the Disrupted Iron Metabolism in Obese Adolescents

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2 Study of Serum Hepcidin as a Potential Mediator of the Disrupted Iron Metabolism in Obese Adolescents Prof. Azza Abdel Shaheed Prof. of Child Health NRC National Research Centre Egypt

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4 Prevalence of childhood overweight and obesity is increasing. Egypt is considered the 1 st African country regarding obesity prevalence & the 14 th worldwide country according to the most recent WHO statistics (in 2010).

5 Iron deficiency continues to be the most prevalent single micronutrient deficiency disease in the world, affecting billions of people. The association between iron status and obesity is one that should be explored, as both have significant public health implications.

6 Unbalanced low cost fast food meals (rich in carbohydrates and fat & low in essential nutrients such as iron) is considered the main reason for the recently interesting association between iron deficiency & obesity.

7 The identification of hepcidin, a 25-amino-acid peptide produced prevalently in the liver and represent the main regulator of intestinal iron absorption and macrophage iron release opened a new era in our understanding of iron metabolism.

8 hepcidin is expressed not only in liver but also in adipose tissue. mrna expression is increased in adipose tissue of obese patients. Hepcidin-inflammation connection may represent the biological framework explaining the association of poor iron status with obesity

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10 1) To determine iron status in obese adolescents. 2)To investigate the relation between serum hepcidin level and iron status in obese adolescents. 3)To study the relation between serum hepcidin level and hs-crp.

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12 1 - Subjects : Fourty adolescents presented with obesity to the Nutritional Clinic at the NRC were included in the study. Inclusion criteria : 1- Male and female adolescents. 2- Age : years old. 3-Obese adolescents with BMI 95th percentile for age and sex. 4 - Simple obesity.

13 Exclusion criteria : 1- Adolescents with chronic conditions. 2- Organic causes of obesity. 3-Children on iron supplements or using medications that affect body weight. 4- Girls with menorrhagia. Controls : Equal number of normal healthy age and sex matched adolescents with BMI = 5th - 84th percentile consulting the pediatric clinic in the NRC for minor illness.

14 Ethical aspect : Written informed consent were obtained from parents after explanation of the aim of the study. 2 - Methods : All patients & controls were subjected to the following : A) Anthropometric measurements: - Weight, height and BMI = Wt ( kg ) / Ht( m2 ) measurements were divided into percentiles and were entered separately to the Egyptian Growth charts for age and sex. - Waist circumference, hip circumference, Waist :hip

15 B) Full medical history : 1. Personal History 2. Socio-demographic data 3. Past History 4. Present History a) Onset,course and duration of gaining weight b) Chronic diseases. c) Chronic blood loss. d) Medications received. e) Obesity related complaints. f) any co-morbidities.

16 5. Family History: Obesity, type 2 diabetes, cardiac disease & hypertension. 6. Diet History: a) During infancy Breast feeding, formula or mixed feeding and time of weaning. b) During childhood

17 7. Life style history: Sedentary lifestyle (TV and computer watching hours), physical activity( frequency and type of activity). 8. Examination: a- General (pulse,blood pressure and temperature). b - Systemic (neurological,cardiac,chest and abdomen).

18 9. Laboratory investigations: a- Haemoglobin b- Serum Iron and Total Iron Binding Capacity (TIBC) c- Serum Ferritin d- Soluble serum transferrin receptor (stfr) e- High sensitive C-reactive protein (hs - CRP) f- Serum Hepcidin

19 Interpretation of results IDA was defined as concurrent ID and anaemia *Laboratory criteria used to diagnose iron deficiency - Serum iron for boys < 60ug/dl,for girls < 50ug/dl. - Serum ferritin < 10 ng/ml. - Serum transferrin saturation 15% (TS= Serum iron / TIBC x 100). Iron deficiency (ID) was defined as 2 abnormal age-corrected iron parameters (iron, ferritin, transferrin and transferrin saturation) *WHO criteria for diagnosis of anaemia: Children with haemoglobin concentration < 11.5 g/dl = anaemic

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21 48% 52% Female Male CASES 33% Female Male 67% CONTROL Sex distribution (NS)

22 Comparison between cases and controls as regards socio-economic levels Cases (n= 40) Controls (n= 40) Sig. Socioeconomic level Below average 4 (10.0%) 2 (5.0%) NS Average 6 (15.0%) 7 (17.5%) Above average 11 (27.5%) 9 (22.5%) High 18 (45.0%) 21 (52.5%) Very high 1 (2.5%) 1 (2.5%)

23 Comparison between cases and controls as regards family history of obesity Cases (n= 40) Control (n= 40) Sig. Family history of Obesity Father 15 (37.5%) 5 (12.5%) Mother 24 (60.0%) 7 (17.5%) Sibling 13 (32.5%) 2 (5.0%)

24 Comparison between cases and controls as regards frequency of obesity related complaints Cases (n= 40) Control (n= 40) Sig. Obesity related complaints 23 (57.5%) 0 (0%) Joint pain 3 (7.5%) 0 (0%) NS Back pain 6 (15%) 0 (0%) S Foot pain 5 (12.5%) 0 (0%) S Arthritis 0 (0%) 0 (0%) Snoring 10 (25%) 0 (0%) Sleep apnea 1 (2.5%) 0 (0%) NS Short of breath 4 (10%) 0 (0%) S

25 Comparison between cases and controls as regards patterns of feeding during infancy Cases (n= 40) Control (n=40) Sig. Type of feeding Breast feeding 5 (12.5%) 27 (67.5%) Formula feeding 22 (55.0%) 6 (15.0%) Mixed feeding 13 (32.5%) 7 (17.5%) Duration of breast feeding (months) 4.2 ± ± 5.2 Age at weaning (months) 7.1 ± ± 1.0 NS

26 Comparison between cases and controls as regards different history data Cases Control Sig. Birth weight (kg) 3.8 ± ± 0.3 < (30.0%) 31 (77.5%) > (70.0%) 9 (22.5%) Pubertal Onset (years ) 11.1 ± ± 0.4 Age of Menarche (years) 12.2 ± ± 0.5 Regular menses 21 (52.5%) 27 (67.5%) NS

27 100% 90% 80% 70% 60% 50% 40% Cases Controls 30% 20% 10% 0% Tanner 2 Tanner 3 Tanner 4 Tanner 5 Comparison between cases and controls as regards pubertal staging according to Tanner classification (NS)

28 m m Hg Cases Controls 30 0 Systolic BP Diastolic BP Comparison between mean values of SBP and DBP in the two studied groups

29 Comparison between cases and controls as regards anthropometric data Cases (n= 40) Control (n= 40) Sig. Weight (kg) 81.3 ± ± 7.0 Height (cm) ± ± 3.8 NS BMI (kg / Ht2) 33.0 ± ± 1.0 Waist circumference (cm) 99.4 ± ± 1.5 Hip circumference (cm) 60.1 ± ± 1.2 Waist: hip (cm) 1.7 ± ± 0.0

30 Comparison between cases and contols as regards different laboratory findings Cases (n= 40) Control (n= 40) Sig. Hb (g/dl) 10.1 ± ± 1.3 Iron (ug]dl) 48.5 ± ± 11.8 TIBC (ug/dl) ± ± 37.1 Transferrin saturation (%) 14.8 ± ± 5.7 Ferritin (ng/ml) 21.7 ± ± 1.7 stfr (ug/dl) 5.6 ± ± 1.9

31 Comparison between mean values of hs-crp in the two studied groups

32 Comparison between mean values of Hepcidin in the two studied groups

33 BMI Hepcidin Correlation between serum hepcidin level and BMI in cases group

34 20 15 hs CRP Hepcidin Correlation between serum hepcidin level and hs -CRP in cases group

35 Iron Hepcidin Correlation between serum hepcidin level and serum iron in cases

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37 In conclusion, the present study shows that the frequency of iron deficiency anaemia was greater in obese

38 Low grade inflammation induced by excessive adiposity evidenced by increased level of hs- CRP could be a reason for the observed low iron levels mediated by increased hepcidin production. This in turn causes reduction in iron absorption and/or increasing iron sequestration. This may represents the missing link between obesity and disrupted iron metabolism.

39 This potential role of hepcidin in the development of iron deficiency in the obese adolescents is supported by: Elevated serum hepcidin levels. Positive correlation between hepcidin and BMI. Negative correlation between hepcidin and serum iron.

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41 Screening for iron deficiency anaemia should be done at regular intervals among obese children and adolescents. Weight loss programs for obese children and adolescents may be essential for correction of iron status by decreasing serum hepcidin level. Intervention studies in overweight children and adolescents should be done to assess the effect of weight loss on circulating hepcidin, iron absorption and iron status.

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