Human Intestinal Peptides Evaluation and Research

Study Overview
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Brief Summary
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The HIPER-1 study is a single centre cross sectional study in which a total of 240 participants (in different metabolic states and surgical models) will receive an Oral Mixed Meal Tolerance Test (OMTT). At baseline and after 30, 60 and 120 minutes the PYY levels, GLP-1 levels, glucose and insulin sensitivity will be measured. The primary endpoint of the study will be the area under the GLP-1 and Peptide - YY curves and insulin sensitivity following the OMTT.

Detailed Description
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Obesity and type 2 diabetes mellitus (T2DM) are increasing worldwide, thus reaching pandemic proportions. Diet, exercise and medication remain the cornerstones of type 2 diabetes mellitus treatment. But, apart from studies demonstrating promising results in some of the developed countries; the long-term success rates of lifestyle and drug modifications are disappointing. In cases where classic strategies proved to be inadequate, broad type of gastrointestinal (GI) surgery methods offer new alternatives to treat obesity and T2DM. The variable levels of incretin stimulation (especially GLP-1) and improved glycaemic control in those with diabetes have been shown following various bariatric techniques. Therefore, investigators aimed to analyze the levels of GLP-1 and Peptide YY hormones together with indices of insulin sensitivity in participants with various health conditions and in participants who underwent different surgical options including sleeve gastrectomy, minigastric bypass, sleeve gastrectomy with ileal transposition and sleeve gastrectomy with transit bipartition.

Official Title
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Effects of Different Metabolic States and Surgical Models on Glucose Metabolism and Secretion of Ileal L-cell Peptides

Conditions
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Obesity, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Other: blood sample analysis


Participation Criteria
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Eligibility Criteria
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For NON-SURGERY GROUPS Inclusion Criteria: GROUP NS-A: Healthy participants, no known disease, no previous surgery, HbA1c<5.7%, BMI<25 kg/m2 (n=30). GROUP NS-B: Obese diabetic, type 2 diabetes diagnosis longer than 3 years; BMI>30 kg/m2 (n=30). GROUP NS-C: Non-obese diabetic, type 2 diabetes diagnosis longer than 3 years; BMI<30 kg/m2 (n=30). GROUP NS-D: Obese non-diabetics, HbA1c<5.7%, No signs and history of T2D, and BMI>30 kg/m2 (n=30). Preferably not on any kind of anti-diabetic drugs or will accept cessation of all anti-diabetic drugs 2 days prior to evaluation. Absence of co-morbidities (dyslipidemia, hypertension, neuropathy, retinopathy, cardiovascular disease, stroke events or lower extremity amputation). Possibility to participate to the quadruplicate measurement protocol. Exclusion Criteria: Anti insulin / islet antibody and glutamic acid decarboxylase antibody (antiGAD) positivity, plasma fasting C-peptide lesser than 1 ng/ml. Liver cirrhosis, severe renal failure, collagen diseases, severe endocrinopathies, blindness. Heart failure, acute myocardial infarction, stroke or transient ischemic attack, unstable angina pectoris. History of malignancy or malignant neoplasm in place, severe inflammatory complications, neurological or cardiovascular in act. Pregnancy Any conditions that at the discretion of the head of the study can represent risk to the participant or could affect the protocol results. For SURGERY GROUPS Inclusion Criteria: Type 2 Diabetic participants who underwent a sleeve gastrectomy, a mini-gastric bypass, a sleeve gastrectomy with ileal transposition or a sleeve gastrectomy with transit bipartition performed more than 6 months ago, but within the last 2 years, with steady weight profile. Preferably not on any kind of anti-diabetic drugs or will accept cessation of all anti-diabetic drugs 2 days prior to evaluation. Absence of or resolved co-morbidities (dyslipidemia, hypertension, neuropathy, retinopathy, cardiovascular disease, stroke events or lower extremity amputation). Possibility to participate to the quadruplicate measurement protocol. Exclusion Criteria: Liver cirrhosis, severe renal failure, collagen diseases, severe endocrinopathies, blindness. Heart failure, acute myocardial infarction, stroke or transient ischemic attack, unstable angina pectoris. History of malignancy or malignant neoplasm in place, severe inflammatory complications, neurological or cardiovascular in act. Pregnancy Any conditions that at the discretion of the head of the study can represent risk to the participant or could affect the protocol results.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| GROUP NS-A<br>Healthy Participants: No known disease, no previous surgery, HbA1c<5.7%, BMI<25 kg/m2 (n=30). Blood sample analysis (Blood samples will be taken for the analysis of GLP-1, Peptide YY, glucose and insulin before and 30-60-120 minutes after Oral Mixed Meal Tolerance Test). | Other: blood sample analysis<br>* Measurement of GLP-1, Peptide YY, Glucose and Insulin before and 30-60-120 minutes after Oral Mixed Meal Tolerance Test.<br>|
| GROUP NS-B<br>Obese, type 2 diabetic: Type 2 diabetes diagnosis longer than 3 years; BMI>30 kg/m2 (n=30). Blood sample analysis (Blood samples will be taken for the analysis of GLP-1, Peptide YY, glucose and insulin before and 30-60-120 minutes after Oral Mixed Meal Tolerance Test). | Other: blood sample analysis<br>* Measurement of GLP-1, Peptide YY, Glucose and Insulin before and 30-60-120 minutes after Oral Mixed Meal Tolerance Test.<br>|
| GROUP NS-C<br>Non-obese, type 2 diabetic: Type 2 diabetes diagnosis longer than 3 years; BMI<30 kg/m2 (n=30). Blood sample analysis (Blood samples will be taken for the analysis of GLP-1, Peptide YY, glucose and insulin before and 30-60-120 minutes after Oral Mixed Meal Tolerance Test). | Other: blood sample analysis<br>* Measurement of GLP-1, Peptide YY, Glucose and Insulin before and 30-60-120 minutes after Oral Mixed Meal Tolerance Test.<br>|
| GROUP NS-D<br>Obese non-diabetic: HbA1c<5.7%, No signs and history of T2D, and BMI>30 kg/m2 (n=30). Blood sample analysis (Blood samples will be taken for the analysis of GLP-1, Peptide YY, glucose and insulin before and 30-60-120 minutes after Oral Mixed Meal Tolerance Test). | Other: blood sample analysis<br>* Measurement of GLP-1, Peptide YY, Glucose and Insulin before and 30-60-120 minutes after Oral Mixed Meal Tolerance Test.<br>|
| Group SG<br>Type 2 Diabetic participants who underwent a sleeve gastrectomy, performed more than 6 months ago, but within the last 2 years, with steady weight profile. Blood sample analysis (Blood samples will be taken for the analysis of GLP-1, Peptide YY, glucose and insulin before and 30-60-120 minutes after Oral Mixed Meal Tolerance Test). | Other: blood sample analysis<br>* Measurement of GLP-1, Peptide YY, Glucose and Insulin before and 30-60-120 minutes after Oral Mixed Meal Tolerance Test.<br>|
| Group MGB<br>Type 2 Diabetic participants who underwent a mini-gastric bypass, performed more than 6 months ago, but within the last 2 years, with steady weight profile. Blood sample analysis (Blood samples will be taken for the analysis of GLP-1, Peptide YY, glucose and insulin before and 30-60-120 minutes after Oral Mixed Meal Tolerance Test). | Other: blood sample analysis<br>* Measurement of GLP-1, Peptide YY, Glucose and Insulin before and 30-60-120 minutes after Oral Mixed Meal Tolerance Test.<br>|
| Group IT<br>Type 2 Diabetic participants who underwent a sleeve gastrectomy with ileal transposition, performed more than 6 months ago, but within the last 2 years, with steady weight profile. Blood sample analysis (Blood samples will be taken for the analysis of GLP-1, Peptide YY, glucose and insulin before and 30-60-120 minutes after Oral Mixed Meal Tolerance Test). | Other: blood sample analysis<br>* Measurement of GLP-1, Peptide YY, Glucose and Insulin before and 30-60-120 minutes after Oral Mixed Meal Tolerance Test.<br>|
| Group TB<br>Type 2 Diabetic participants who underwent a sleeve gastrectomy with transit bipartition, performed more than 6 months ago, but within the last 2 years, with steady weight profile. Blood sample analysis (Blood samples will be taken for the analysis of GLP-1, Peptide YY, glucose and insulin before and 30-60-120 minutes after Oral Mixed Meal Tolerance Test). | Other: blood sample analysis<br>* Measurement of GLP-1, Peptide YY, Glucose and Insulin before and 30-60-120 minutes after Oral Mixed Meal Tolerance Test.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma GLP-1 and P-YY measurements by ELISA in participants with various health conditions. | Measurements will be performed before and 30-60-120 minutes after a mixed meal test and results will be expressed as pmol/L. | Up to 6 months. | 
| Plasma GLP-1 and P-YY measurements by ELISA in participants treated by different bariatric and metabolic surgical techniques. | Measurements will be performed before and 30-60-120 minutes after a mixed meal test and results will be expressed as pmol/L. | Up to 6 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body Mass Index (BMI) in participants with various health conditions. | BMI will be expressed in kg/m^2 (weight in kilograms and height in meters). | Up to 6 months. | 
| Body Mass Index (BMI) in participants treated by different bariatric and metabolic surgical techniques. | BMI will be expressed in kg/m^2 (weight in kilograms and height in meters). | Up to 6 months. | 
| Waist and hip circumference in participants with various health conditions. | Waist and hip circumferences will be expressed as centimeters. | Up to 6 months. | 
| Waist and hip circumference in participants treated by different bariatric and metabolic surgical techniques. | Waist and hip circumferences will be expressed as centimeters. | Up to 6 months. | 
| Plasma glucose levels in participants with various health conditions. | Measurements will be performed before and 30-60-120 minutes after a mixed meal test. Plasma glucose levels will be measured by Enzymatic Hexokinase method and results will be expressed as mg/dl. | Up to 6 months. | 
| Plasma glucose levels in participants treated by different bariatric and metabolic surgical techniques. | Measurements will be performed before and 30-60-120 minutes after a mixed meal test. Plasma glucose levels will be measured by Enzymatic Hexokinase method and results will be expressed as mg/dl. | Up to 6 months. | 
| Plasma insulin levels in participants with various health conditions. | Measurements will be performed before and 30-60-120 minutes after a mixed meal test. Plasma insulin levels will be measured by ECLIA method and results will be expressed as mU/ml. | Up to 6 months. | 
| Plasma insulin levels in participants treated by different bariatric and metabolic surgical techniques. | Measurements will be performed before and 30-60-120 minutes after a mixed meal test. Plasma insulin levels will be measured by ECLIA method and results will be expressed as mU/ml. | Up to 6 months. |