Quantification of the Incretin Effect in Healthy Subjects and Patients With Type 2 Diabetes

Study Overview
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Brief Summary
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Patients with T2DM lac a sufficient incretin response after oral glucose intake. It has only been tested using 50g of glucose. We don't know if patients with T2DM are capable of regulating the incretin effect like healthy people in responds to different amounts of glucose intake. The aim of the present study is to quantify the incretin effect in healthy subjects and in patients with T2DM during increasing amounts of oral glucose challenges. The proposed studies will answer important questions on the mechanisms underlying T2DM and be of importance in relation to future preventive- and treatment strategies.

Detailed Description
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The impaired incretin effect in patients with type 2 diabetes mellitus (T2DM) has previously only been evaluated using a glucose load of 50 g, and it is uncertain whether patients with T2DM are capable of regulating their incretin effect equivalent to healthy subjects. Furthermore, it is of great interest to quantify the secretion of GIP and GLP-1 during increasing glucose loads in both patients with T2DM and in healthy subjects in order to evaluate whether an increased secretion of one or both of the two incretin hormones contributes to the regulation of the incretin effect. The aim of the present study is to quantify the incretin effect in healthy subjects and in patients with T2DM during increasing amounts of oral glucose challenges and corresponding isoglycemic iv glucose challenges. The proposed studies will answer important questions on the pathophysiology underlying T2DM and be of importance in relation to future preventive- and treatment strategies. Eight patients with T2DM and 8 matched healthy subjects will be evaluated with oral glucose tolerance tests (OGTT) using increasing glucose loads (25, 50 and 100 g glucose) and isoglycemic iv glucose tolerance tests imitating the glucose concentrations as obtained during the oral glucose loads. The results will describe the regulation of the incretin effect in patients with T2DM and, thereby, contribute to the clarification of the pathophysiology of the postprandial hyperglycemia characterizing these patients.

Official Title
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Quantification of the Incretin Effect in Healthy Subjects and Patients With Type 2 Diabetes Using Increasing Amounts of Oral Glucose Challenges

Conditions
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Incretin Effect

Intervention / Treatment
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* Other: Oral Glucose Tolerance Test
* Other: Isoglycemic clamp
* Other: Gastric emptying rate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cases Caucasians with T2DM according to WHO's criteria Normal Hemoglobin Agree to participate (orally and in writing) HbA1c: 6.5-9 % BMI: 23-35 kg/m2 Exclusion Criteria:Cases Liver disease (ALAT > 2 x normal level) Diabetic nephropathy (s-creatinin > 130 µM or albuminuria) Diabetic neuropathy (anamnestic) Proliferative diabetic retinopathy (anamnestic) Medical treatment witch cannot be stopped for 12 hours Pregnancy or breastfeed Treatment with Insulin or glitazones Inclusion Criteria: Control group Caucasians Normal oral glucose tolerance according to WHO's criteria Normal Hemoglobin Agree to participate (orally and in writing) BMI: 23-35 kg/m2 Exclusion Criteria: Control group Liver disease (ALAT > 2 x normal level) Impaired function of the kidney (s-creatinin > 130 µM or albuminuria) Directly related til to someone suffering from diabetes mellitus Medical treatment witch cannot be stopped for 12 hours Pregnancy or breastfeed

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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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 |
| --- | --- |
| T2DM<br>T2DM patients (WHO-criteria) | Other: Oral Glucose Tolerance Test<br>* The test is preformed 3 times with 3 different amounts of glucose (25g, 75g and 125g) deluded in 300ml of water.<br>Other: Isoglycemic clamp<br>* I.v. glucose infusion initiating the glucose responds curves from the OGTT<br>Other: Gastric emptying rate<br>* Paracetamol absorption test. Intake of 1,5g of paracetamol followed by measuring the absorption curve<br>|
| CTRL<br>Healthy control subjects matched individually to the cases. | Other: Oral Glucose Tolerance Test<br>* The test is preformed 3 times with 3 different amounts of glucose (25g, 75g and 125g) deluded in 300ml of water.<br>Other: Isoglycemic clamp<br>* I.v. glucose infusion initiating the glucose responds curves from the OGTT<br>Other: Gastric emptying rate<br>* Paracetamol absorption test. Intake of 1,5g of paracetamol followed by measuring the absorption curve<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progress in Incretin effect in patients with T2DM compared with healthy subjects |  | 4 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GIP and GLP-1 responscurvs |  | 4 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 2 diabetes mellitus, Incretin effect, Glucagon-Like Peptide 1, Gastric Inhibitory Polypeptide