Study of Sleeve Gastrectomy on Iron Intestinal Absorption in Morbidly Obese Patients
Study of Sleeve Gastrectomy on Iron Intestinal Absorption in Morbidly Obese Patients
Subject: Evaluation of the impact of obesity surgery by sleeve gastrectomy on intestinal iron
 absorption of morbid obese subjects.

 Control of intestinal absorption of iron is mediated by hepcidin, which is expressed in
 adipose tissue and that its expression is increased in morbidly obese subjects. The working
 hypothesis is that this increase could explain the high prevalence of systemic iron depletion
 observed in obese patients.

 Main objective: Assess the impact of the decrease in fat mass induced by surgery in obese
 patients on the intestinal absorption of iron (evaluated by measuring the expression of iron
 transporters in the duodenum)
Study Rationale a high prevalence of iron deficiency and anemia has recently been
 characterized in obese patients and may be related to the stage of low-grade systemic
 inflammation associated with obesity

 Control of intestinal absorption of iron is mediated by hepcidin, a small circulating peptide
 synthesized primarily by the liver. the synthesis of hepcidin is increased in inflammatory
 condition and very recently it was shown that hepcidin is expressed in adipose tissue and
 that its expression is increased in morbidly obese subjects

 The working hypothesis is that this increase could explain the high prevalence of systemic
 iron depletion observed in these patients. the use of bariatric surgery is becoming more
 common to treat severe obesity (BMI above 35 kg / m2)

 The sleeve gastrectomy, recently introduced, involves a very significant weight loss.
 however, its impact on iron deficiency and anemia are not known

 main objective Assess the impact of the decrease in fat mass induced by surgery in obese
 patients on the intestinal absorption of iron (evaluated by measuring the expression of iron
 transporters in the duodenum

 Secondary objectives:

 -  Assess the impact of the decrease in fat mass induced by surgery in obese patients on
 the concentration of circulating hepcidin.

 -  To study the correlation between the level of expression of iron transporters in the
 duodenum and the plasma concentration of circulating hepcidin

 -  Search for a correlation between the level of hepcidin expression in subcutaneous
 adipose tissue and visceral and concentration of plasma hepcidin before surgery.

 -  Evaluate the effects of sleeve gastrectomy surgery on haematological and iron status of
 obese patients.

 Selection criteria for patients:

 Inclusion criteria: female subjects, having a body mass index > 40 kg/m2 (or > 35 kg/m2 with
 comorbidity) justifies a obesity surgery, For whom the indication of obesity surgery has been
 laid, the collective decision is taken in consultation, as part of care between different
 specialty (physicians, surgeons, psychiatrists ...)

 Non-inclusion criteria strictly less than age 18 years or strictly greater than 60 years,
 history of bariatric surgery or stomach, hepatic cytolysis (transaminases > 3n) during cancer
 treatment (radio or chemotherapy treatments) coefficient of transferrin saturation > 45%;
 known history of any of the following: hematologic disease requiring transfusions,
 hemochromatosis, Wilson's disease (because of known interference between metabolism of iron
 and copper), Chronic inflammation; Patient did not receive a medical examination; Patient did
 not give informed consent in writing, not affiliated with Patient Social Security or CMU (
 universal health coverage) (recipient or beneficiary), known pregnancy

 Number needed: 88 patients enrolled

 Total duration of the study: 54 months

 Duration of participation for each patient: 24 months

 Duration of inclusion: 30 months

 Methods:

 Prospective open multicenter study cognitive. 4 visits are planned as part of this research
 with some specificity for the different centers.

 Visit 1: Presentation of the study and obtaining consent. Visit 2: consultation with
 implementation of a multidisciplinary assessment of duodenal biopsies by gastroscopy,
 additional laboratory tests and a pregnancy test if necessary.

 Visit 3: surgery (sleeve gastrectomy) with adipose tissue biopsies. Visit 4: creation of a
 consultation with multidisciplinary assessment of duodenal biopsies by gastroscopy and
 additional laboratory tests.

 Examinations required specifically for research: duodenal biopsies, additional laboratory
 tests, biopsies of adipose tissue and pregnancy test (dipstick) for all premenopausal women
 (contraceptives or not).

 Primary assessment criteria:

 The intestinal absorption of iron will be assessed by the level of expression of iron
 transporters (DMT1 and ferroportin) mRNA (messenger ribonucleic acid) level by RT-qPCR
 (reverse transcription quantification polymerase chain reaction) and at the protein level by
 Western blot.

 secondary assessment (s) criteria (s) The concentration of hepcidin plasma will be measured
 by ELISA in adipose tissue, the level of hepcidin expression is quantified by RT-qPCR .

 The haematological will assess the presence of anemia (hemoglobin less than 12g/dl) its micro
 or macrocytic hemolytic and / or regenerative
Inclusion Criteria:

 -  morbid obese women selected for bariatric surgery

 Exclusion Criteria:

 -  non obese patients, less than 18 years old, haematological disease with need of blood
 transfusions