Adipocyte, Insulin-resistance and Immunity : Evaluation of Interleukin-7 in Lipodystrophies According to Fat Mass and Glucose Metabolism
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Enrollment
- 126
- Locations
- 10
- Primary Endpoint
- Measure of blood Interleukin 7
Study Overview
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.
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Cross Sectional
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
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
- •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
Arms & Interventions
normal
Patients with no overweight and no type 2 diabetes
lipodystrophy
patients with a lipodystrophy, most are diabetics
obese non diabetics
Patients with obesity (BMI <30kg/m2), without diabetes
obese diabetics
Patients with obesity (BMI <30 kg/m2), with diabetes
Outcomes
Primary Outcomes
Measure of blood Interleukin 7
Time Frame: 1 day
Secondary Outcomes
- measure of blood interleukin 9(1 day)
- measure of blood IL-6(1 day)
- measure of blood IL-18(1 day)
- measure of blood leptin(1 day)
- Blood count of dendritic cells(1 day)
- Count of blood lymphocytes T(1 day)
- measure of blood Interleukins 2(1 day)
- measure of blood adiponectin(1 day)
- Blood count of monocytes/macrophages(1 day)
- measure of blood Interleukin 15(1 day)
- measure of blood TNF(1 day)
- measure of blood IL-1(1 day)
- measure of blood IL-8(1 day)
- measure of blood IL-10(1 day)