Effect of Treatment With Metformin in Type 2 Diabetes Patients on Alternative Genes Splicing

Study Overview
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Brief Summary
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Main objective : Show that treatment with metformin in patients with type 2 diabetes has an effect on alternative splicing of the insulin receptor. Secondary objective : demonstrate that the effect on the ratio A/isoform B isoform with discontinuation of treatment with metformin can be réversé by the resumption of metformin treatment.

Official Title
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Effect of Treatment With Metformin in Type 2 Diabetes Patients on Alternative Genes Splicing Whose Maturation Depends on the Protein HuR, Including Gene Encoding Insulin Receptor

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: Metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 Diabetic patients usually treated with metformin (≥ 1400 mg/day), associated or not to other oral anti-diabetic treatment or. injection treatment Patients major. Patients with a social security number Patients having signed a consent to participate in the study Exclusion Criteria: Intolerance metformin Patients with type 1. Patients on pioglitazone or rosiglitazone Renal failure by an anomaly of the creatinine clearance (< 60 mL/min). Patients pregnant or likely to be.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm1<br>During their visit of consultation on the follow-up to the type 2 diabetes, les patients will be selected on the basis of active metformin treatment at a dose greater than or equal to 1400 mg/day. Patients will have to achieve a 10 ml blood sample. The blood will be processed by Ficoll gradient centrifugation to remove the red cells and isolate circulating leukocytes: this stage will be conducted in the CERITD. Analysis on circulating leukocytes and in particular the quantification of expressions of isoforms A and B of the INSR1 by quantitative RT - PCR gene will be conducted in the laboratory of the Professor Marc Peschanski (unit INSERM 861 I - STEM of Evry). After inclusion in the study to J0, metformin treatment will be interrupted between J1 and J30, replaced by Januvia 100 mg/day dose, then resumed at J31. | Drug: Metformin<br>* After inclusion in the study to J0, metformin treatment will be interrupted between J1 and J30, replaced by Januvia 100 mg/day dose, then resumed at J31.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of expression of isoforms A and B of the insulin receptor using quantitative RT PCR | comparison of the A isoform (without inclusion of exon 11) and B isoform (with inclusion of exon 11) ratio of the receptor in insulin, during the first period (without metformin) and the second period (with metformin) | inclusion (baseline), 30th days and 60th days |