The effect of treatment on ghreline and hepsidin levels in iron deficiency anemia

ABSTRACT Introduction: Anemia is a global health problem. The most common cause of anemia is iron deficiency anemia. Even if iron deficiency anemia (IDA) treatment seems to be simple, problems in compliance with oral iron therapy are frequently seen. It has been shown that medications are not used regularly or discontinued due to weight gain during the treatment process. Ghrelin and hepcidin are recently investigated parameters related to appetite associated with iron deficiency . Ghrelin is a hormone secreted from the fundus of stomach, which signals hunger to the brain. It increases appetite and food intake through the central or peripheral route.Hepcidin is a homeostatic regulator of intestinal iron absorption. We hope that our study will provide information that will contribute to clarifying the numerous symptoms seen in IDA and the compliance problems associated with weight gain during treatment. Material and Methods: 120 patients, aged >18 years, who referred to Düzce University Training and Research Hospital Internal medicine or Hematology clinics between October 2015 and October 2016 and diagnosed iron deficiency anemia according to WHO or Turkish Society of Hematology criteria (Hemoglobin values of <12 gr/dl in women and <15 gr/dl in men, ferritin <15 ng/mL) were included in the study. Forty-three subject who met exclusion criteria or who did not give informed consent were excluded from the study. The study was completed with 87 patients and a control group consisted of 50 healthy people. Information about age, gender, weight, height, body mass index (BMI), waist-hip circumference and blood samples were taken from the patient and control groups. The treatment of IDA was done according to the dose and method recommended by the responsible physician, the researchers did not have any effect on the treatment. Measurements and blood tests were repeated in the patient group after normalization of the anemia parameters (hemoglobin, mean corpuscular volume, ferritin), not before the third month of treatment. Hepcidin and ghrelin levels were examined once in the control group and twice in the patient group, before and after treatment. Results: When the patient and control groups were compared, there was no significant difference in terms of age, sex, height, weight, BMI, waist and hip circumference. There was a significant increase in terms of weight, BMI, waist and hip circumference measurements after treatment in the patient group (p <0.001). Patients had a mean increase of 1.15 kg after treatment (p <0.001), a rise in VKI to 25.86 kg/m2 from 26.33 kg/m2 (p <0.001), an increase of of 0.81cm in waist circumference and an increase of 0.81cm in hip circumference (p <0.001) but the waist/hip ratio remained constant. The pretreatment plasma hepcidin and ghrelin levels of the patient group were significantly lower than those of the control group (80 ± 21 ng/ml vs. 179 ng/ml p <0.001 for hepcidine, 152 ± 119 pq / ml vs 213 ± 167 for ghrelin, p = 0.026). After treatment, the levels of hepcidine was significantly increased compared to the pre-treatment levels (80 ± 21 ng/dl vs 92 ± 13 ng/dl, p <0.001). Although an increase in the plasma ghrelin levels was encountered after treatment, it was not statistically significant (152 ± 119 pq/ml vs 164 ± 150 pq/ml, p=0.589). When correlations of individual increase in ghrelin levels were examined, positive correlation was found between increase in ghrelin levels and both weight gain and increase in BMI. Conclusion: In patients with iron deficiency anemia, we found that hepcidin level, related to intestinal iron absorption, and ghrelin level, appetite-related hormone, was significantly low compared to the healthy control group. After treatment, both of these markers increased, however only the increase in hepcidin was significant but not related with weight gain. The increase in ghrelin probably did not reach statistical significance due to the physiological suppression due to weight gain. However, when the patient-based weight gain was examined, a positive correlation was found with increasing ghrelin. We hope that our study, demonstrating the assosiations of change in ghrelin and hepsidin levels with the lack of appetite which is an important symptom of the IDA, and the weight gain associated with treatment, will shed light on more extensive and controlled studies in this regard. Keywords: Iron deficiency anemia, ghrelin, hepcidin, appetite, weight gain