Identification of Human Biomarkers Predictive of Diabetes Remission in Type 2 Diabetes Patient (BARIAKINES)

Study Overview
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Brief Summary
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This study focuses on identifying potentially predictive human circulating adipocyte and muscle biomarkers of diabetes remission after bariatric surgery in obese type 2 diabetic (T2D) subjects.

Detailed Description
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The study team at the Institute of Metabolic and Cardiovascular Diseases has recently identified several potential biomarkers (secreted by skeletal muscle and adipose tissue) of glucose homeostasis control using secretomic and metabolomic analyses. The goal of this study is to assess whether the addition of 9 adipocytes and myocytes plasma level could be associated with type 2 diabetes remission one year after bariatric surgery and would improve established clinical models of prediction of diabetes remission. Thus, obese type 2 diabetes patients undergoing bariatric surgery will have 2 blood samples, a muscle sample and one adipose tissue sample withdrawn during the study. From those samples, concentrations of 9 candidate proteins is measured : GDF6, INHBB, IL17B, TGFB2, TIMP1, VTN, MDK, GDF15, and apoM

Official Title
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Identification of Human Circulating Adipocyte and Muscle Biomarkers Potentially Predictive of Diabetes Remission After Bariatric Surgery in Obese and Type 2 Diabetic Subjects.

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Procedure: blood samples
* Procedure: collection of body tissues
* Procedure: routine care procedure


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Obese patients of at least grade 2 (body mass index ≥ 35 kg/m²) Type 2 diabetics About to undergo bariatric surgery at the Toulouse University Hospital Over 18 and under 70 years of age Affiliated or beneficiaries of a social security plan. Having provided a free, informed and written consent, signed (at the latest on the day of inclusion and before any examination required by the research). Exclusion Criteria: Type 1 diabetic subjects or Maturity-Onset Diabetes of the Youth. Pregnant and breastfeeding women. Vulnerable persons as defined in the Public Health Code: protected adults (guardianship, curators), unable to express their consent.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Prevention
Intervention Model: Single Group Assignment
Interventional Model Description: This is an exploratory pilot study, comparing for the first time in humans, the remission of type 2 diabetes, one year after bariatric surgery, with regard to circulating concentrations of 9 candidate proteins measured at T0.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: study arm<br>This arm consists of obese patients with type 2 diabetes who are scheduled for bariatric surgery. | Procedure: blood samples<br>* - Research blood sample: 2 additional tubes compared to the classic sample for the analysis of the 9 research molecules.<br>Procedure: collection of body tissues<br>* removal of intra-abdominal fat and muscle tissue<br>Procedure: routine care procedure<br>* Routine care blood sample: Full vitamin panel, CBC, liver panel, urea, creatinine, blood ionogram, blood calcium, phosphorus, magnesium at all visits, except the morning of surgery when only ß HCG (for women of childbearing age), HbA1c. clinical examination : weight, height, waist measurement, cardiovascular examination, digestive system examination. dosage of ß HCG for womens.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between plasma levels of 9 target molecules and diabetes remission | The correlation between plasma levels of 9 target molecules (1 for each molecule) and diabetes remission will be evaluated through plasmatic dosages. The plasma determination of apolipoprotein M will be performed by mass spectrometry, and the 8 other molecules will be determined by the ELISA technique. The dosage is measured in mmol/l. Complete remission of T2DM will be defined according to the following criteria: HbA1c < 5.7% and fasting blood glucose < 5.6 mmol/l. Partial remission of T2DM will be defined as: HbA1c between 5.7 and 6.5% and fasting blood glucose between 5.6 and 6.9 mmol/l without any antidiabetic treatment. Finally, the absence of remission will include patients whose HbA1c is greater than or equal to 6.5% or fasting blood glucose greater than or equal to 7 mmol/l with one or more antidiabetic treatments. | Immediately before the Surgery (day 0) | 
| Correlation between plasma levels of 9 target molecules and diabetes remission | The correlation between plasma levels of 9 target molecules (1 for each molecule) and diabetes remission will be evaluated will be evaluated through plasmatic dosages. The plasma determination of apolipoprotein M will be performed by mass spectrometry, and the 8 other molecules will be determined by the ELISA technique. The dosage is measured in mmol/l. Complete remission of T2DM will be defined according to the following criteria: HbA1c < 5.7% and fasting blood glucose < 5.6 mmol/l. Partial remission of T2DM will be defined as: HbA1c between 5.7 and 6.5% and fasting blood glucose between 5.6 and 6.9 mmol/l without any antidiabetic treatment. Finally, the absence of remission will include patients whose HbA1c is greater than or equal to 6.5% or fasting blood glucose greater than or equal to 7 mmol/l with one or more antidiabetic treatments. | At 3 months post-surgery | 
| Correlation between plasma levels of 9 target molecules and diabetes remission | The correlation between plasma levels of 9 target molecules (1 for each molecule) and diabetes remission will be evaluated will be evaluated through plasmatic dosages. The plasma determination of apolipoprotein M will be performed by mass spectrometry, and the 8 other molecules will be determined by the ELISA technique. The dosage is measured in mmol/l. Complete remission of T2DM will be defined according to the following criteria: HbA1c < 5.7% and fasting blood glucose < 5.6 mmol/l. Partial remission of T2DM will be defined as: HbA1c between 5.7 and 6.5% and fasting blood glucose between 5.6 and 6.9 mmol/l without any antidiabetic treatment. Finally, the absence of remission will include patients whose HbA1c is greater than or equal to 6.5% or fasting blood glucose greater than or equal to 7 mmol/l with one or more antidiabetic treatments. | At 12 months post-surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Areas under the ROC curves of different logistic regression models fitted to known clinical prediction scores (DiaRem, Ad-DiaRem). | The DiaRem and Ad-DiaRem scores are weighted scoring systems based on initial pre-surgical factors that were specifically created to predict remission of type 2 diabetes after bariatric surgery. | At 3 months post-surgery | 
| Areas under the ROC curves of different logistic regression models fitted to known clinical prediction scores (DiaRem, Ad-DiaRem). | The DiaRem and Ad-DiaRem scores are weighted scoring systems based on initial pre-surgical factors that were specifically created to predict remission of type 2 diabetes after bariatric surgery. | At 12 months post-surgery | 
| the kinetics of the plasma levels of each of the 9 molecules studied | the kinetics of the plasma levels of each of the 9 molecules will be studied by measuring each factor on an empty stomach: the day of the operation in the digestive surgery department. | Immediately before the Surgery (day 0) | 
| the kinetics of the plasma levels of each of the 9 molecules studied | the kinetics of the plasma levels of each of the 9 molecules will be studied by measuring each factor on an empty stomach: the day of the operation in the digestive surgery department. | At 3 months after the surgery | 
| the kinetics of the plasma levels of each of the 9 molecules studied | the kinetics of the plasma levels of each of the 9 molecules will be studied by measuring each factor on an empty stomach: the day of the operation in the digestive surgery department. | At 12 months after the surgery | 
| The expression level of genes encoding 9 biomarkers in the adipocyte and the muscle cell | The expression level of the genes encoding 9 biomarkers in the adipocyte and the muscle cell will be evaluated by measuring the mRNA quantities of the genes of these 9 proteins | At the day of the inclusion | 
| The expression level of genes encoding 9 biomarkers in the adipocyte and the muscle cell | The expression level of the genes encoding 9 biomarkers in the adipocyte and the muscle cell will be evaluated by measuring the mRNA quantities of the genes of these 9 proteins | At 3 months after surgery | 
| The expression level of genes encoding 9 biomarkers in the adipocyte and the muscle cell | The expression level of the genes encoding 9 biomarkers in the adipocyte and the muscle cell will be evaluated by measuring the mRNA quantities of the genes of these 9 proteins | At 12 months after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obesity, Bariatric Surgery Candidate, Proteins, Biomarkers