Adipocyte, Insulin-resistance and Immunity : Evaluation of Interleukin-7 in Lipodystrophy, Diabetes and Obesity

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Brief Title

Adipocyte, Insulin-resistance and Immunity : Evaluation of Interleukin-7 in Lipodystrophy, Diabetes and Obesity

Official Title

Adipocyte, Insulin-resistance and Immunity : Evaluation of Interleukin-7 in Lipodystrophies According to Fat Mass and Glucose Metabolism

Brief Summary

      White adipose tissue-related diseases spread from excess (obesity) to lack (lipoatrophies)
      through aberrant distribution (lipodystrophies), these 3 different disorders being
      paradoxically able to induce a metabolic insulin resistance syndrome. The respective part of
      quantitative and qualitative anomalies of adipose tissue, gluco- and lipo-toxicity, liver and
      muscle insulin resistance, low-grade fat inflammation and immune alterations are not
      perfectly understood in the metabolic syndrome yet. Therefore, the aim of this study is to
      assess different cytokines, especially interleukin 7, and metabolic parameters as well as fat
      mass distribution with DEXA and RMN, in different models of fat distribution, including
      normal-weight, obese and lipodystrophic patients. A plasma serum, gene and adipose tissue
      bank will be constituted at the same time to improve our knowledge in disorders linking fat
      mass, insulin resistance and immunity, especially in lipodystrophies, a rare monogenic model
      of insulin resistance.
    

Detailed Description

      Rational: In reason of its ability to store fatty acids and to secrete numerous
      pro-inflammatory cytokines, the adipocyte appears as a key cell in the regulation of energy
      metabolism and immune response. Moreover, it has been recently shown that adipocytes play a
      role in the recruitment of cells involved in innate and adaptive immunity in adipose tissue.

      White adipose tissue-related diseases are numerous, spreading from excess (obesity) to a
      complete (lipoatrophies) or partial lack (lipodystrophies), these 3 different disorders being
      paradoxically able to induce a metabolic insulin resistance syndrome.

      Among the involved cytokines, interleukin-7 (IL-7), mostly known for its immune functions,
      also participates to the quantitative and qualitative balance of fat mass. Thus, IL-7
      over-expression in an animal model induces a lipodystrophic syndrome with insulin resistance
      whereas in humans, a preliminary study shows that LMNA-linked lipodystrophies are associated
      with an increase of blood IL-7 levels. IL-7 also participates to reactivation of autoimmunity
      in patients suffering from auto-immune type 1 after islet transplantation.

      Therefore, the aim of this study is to assess different cytokines, especially interleukin 7,
      and metabolic parameters levels as well as fat mass distribution, in different models of fat
      distribution, including normal-weighed, obese and lipodystrophic patients. A plasma serum,
      gene and tissue bank will be constituted in order to improve our knowledge in disorders
      linking fat mass, insulin resistance and immunity, especially in lipodystrophies, a rare
      monogenic model of insulin resistance.

      Patients: The included patients correspond to subjects of either normal body weight, or
      obese, or suffering from lipodystrophic syndrome, whatever their type 2 diabetes status.

      Methods: Blood IL-7 levels, other immune and/or pro-inflammatory cytokines, lymphocytes
      immuno-phenotype as well as metabolic parameters will be characterized. Fat mass will be
      assessed with non-invasive methods (DEXA and RMN). A plasma, serum and gene bank will be
      constituted. As well as an adipose tissue bank in patients who will have a surgery
      (especially plastic surgery in lipodystrophic patients), in order to cryo-preserve it and to
      define the inflammatory status of this tissue thanks to histological and molecular analysis.

      Main judgment criteria: The main judgment criteria will be IL-7 blood levels in the different
      groups according to fat mass and metabolic parameters. The hypothesis is that in humans the
      quantitative and /or qualitative disturbances of adipose tissue are associated with an
      increase of IL-7 levels and the development of insulin-resistance.

      Awaited results and possible implications: this study will allow to better delineate the
      immune and inflammatory component associated with alterations of fat mass distribution and
      glucose metabolism. Our approach combining clinical investigation and ex vivo and laboratory
      analysis is original and should allow to better understand the cellular mechanisms
      responsible for the inflammatory process originated in white adipose tissue and accompanying
      the disorders of this tissue- more especially lipodystrophic syndromes - opening new
      therapeutic perspectives in common human diseases (obesity, diabetes) on the one hand, and a
      rare disease (lipodystrophy) on the other hand.
    


Study Type

Observational


Primary Outcome

Measure of blood Interleukin 7

Secondary Outcome

 measure of blood Interleukins 2

Condition

Lipodystrophy


Study Arms / Comparison Groups

 normal
Description:  Patients with no overweight and no type 2 diabetes

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information



Estimated Enrollment

126

Start Date

June 2010

Completion Date

June 2015

Primary Completion Date

June 2015

Eligibility Criteria

        Inclusion Criteria:

          -  Male and Female

          -  More than 18 years old

          -  with lipodystrophic syndrome (familial, partial, genetically determined), diabetics or
             not, obese or not

          -  Patients with lipodystrophy non related to a lamine A/C gene mutation, diabetics or
             not, obese or not

          -  Obese without diabetes (BMI> 30)

          -  Obese (BMI>30) and diabetes according to ADA criteria

          -  Normal weight patients (18< BMI< 25)

          -  Agreement for the establishment of a serum bank and a plasma bank

        Exclusion Criteria:

          -  Unable to receive enlightened information

          -  Refusal to sign the consent

          -  Corticosteroids (including inhaled), other immunosuppressing treatments (systemic
             disease for example) or immunomodulators (eg interferon);

          -  Creatinin > 15 mg / L

          -  Sepsis

          -  Progressing cancers or autoimmune diseases;

          -  Treatment, disease or other condition that may affect the rate of IL-7 (as some
             contraceptives with estrogens)

          -  Bleeding disorders (due to disease or treatment)

          -  Active alcohol Intoxication

          -  Psychiatric pathology (after psychiatric consultation)

          -  Active infection including hepatitis C or HIV;

          -  Age under 18 years

          -  Participation in another study excluded the possibility of participating in another
             protocol

          -  BMI > 60

          -  Secondary diabetes

          -  No social security

          -  Pregnant or lactating women, patients under guardianship, persons deprived of liberty
      

Gender

All

Ages

18 Years - 65 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

marie christine VANTYGHEM, pHd, , 

Location Countries

France

Location Countries

France

Administrative Informations


NCT ID

NCT01784289

Organization ID

2009_09/0941

Secondary IDs

2009-A01169-48

Responsible Party

Sponsor

Study Sponsor

University Hospital, Lille


Study Sponsor

marie christine VANTYGHEM, pHd, Principal Investigator, Lille University Hospital


Verification Date

February 2017