Involvement of Extrapancreatic Factors on Gastrointestinal-mediated Glucose Disposal

Study Overview
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Brief Summary
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We want to investigate the mechanisms of extrapancreatic effects on gastrointestinal-mediated glucose disposal. In order to do so we will perform oral glucose tolerance tests and isoglycemic intravenous glucose infusions in total pancreatectomised patients and in healthy controls.

Detailed Description
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In the current project we wish to identify the possible contribution of extrapancreatic effects on gastrointestinal-mediated glucose disposal (GIGD). GIGD reflects the percentage of an individual's glucose disposal following oral glucose tolerance test (OGTT) which is caused by the oral route of glucose administration. In healthy subjects GIGD amounts to  60%. GIGD describes not only the impact of the incretin effect (insulinotropic substances released upon intestinal stimulation) but includes all factors affecting glucose disposal differently during oral vs. iv administration of glucose (including neural reflexes, activation of afferent nerves in the intestinal mucosa, differences in glucagon secretion, hepatic glucose production and first-pass hepatic uptake of glucose, differences in portal and venous blood glucose concentrations and/or at the present unknown factors. It is likely that the incretin effect (pancreatic effect) constitutes a major contributor to GIGD, but so far it has been impossible to discriminate between pancreatic and extrapancreatic mechanisms underlying GIGD

Official Title
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Involvement of Extrapancreatic Factors on Gastrointestinal-mediated Glucose Disposal

Conditions
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Diabetes

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pancreatectomized patients Caucasians above 18 years of age who have undergone total pancreatectomy Normal haemoglobin Informed consent Healthy Subjects Normal fasting plasma glucose (FPG) and normal HbA1C (according to the World Health Organization (WHO) criteria) Normal haemoglobin Age above 18 years Informed consent Exclusion Criteria: Pancreatectomized patients Inflammatory bowel disease Operation within the last 3 months Ongoing chemotherapy or chemotherapy within the last 3 months Ostomy Nephropathy (serum creatinine >150 µM and/or albuminuria) Severe liver disease (serum alanine aminotransferase (ALAT) and/or serum aspartate aminotransferase (ASAT) >3×normal values) Pregnancy and/or breastfeeding Age above 80 years Any condition that the investigator feels would interfere with trial participation Healthy Subjects Diabetes mellitus (DM) Prediabetes (impaired glucose tolerance and/or impaired FPG) First degree relatives with DM Inflammatory bowel disease Intestinal resection and/or ostomy Nephropathy (serum creatinine >150 µM and/or albuminuria Liver disease (ALAT and/or serum ASAT >2×normal values) Pregnancy and/or breastfeeding Age above 80 years Any condition that the investigator feels would interfere with trial participation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gastrointestinal-mediated glucose disposal (GIGD) | GIGD will be calculated based on the amounts of glucose utilised during the two glucose administrations forms, OGTT and IIGI (GIGD (%) = 100%×(glucoseOGTT-glucoseIIGI)/glucoseOGTT) | Calculated when the study days are all complete. approximately in 6month | 
| plasma Glucagon |  | Glucagon will be measured at time points: -30,-15,0,10,20,30,50,70,90,120,150,180 min on all days. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| endogenous glucose production | calculated based on infusions of stable isotope marked glucose | Endogenous glucose production will be calculated based on blood samples at time points: -30,-15,0,10,20,30,50,70,90,120,150,180 min on all days. | 
| Incretin Hormones | GIP, GLP-1 | incretin hormone levels will be measured at time points: -30,-15,0,10,20,30,50,70,90,120,150,180 min on all days. | 
| Satiety, hunger, appetite | Will be measured with visual analogue scales (VAS) | Satiety, hunger and appetite will be measured at time points:0,30,60,90,120,150,180 min during each day. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gastrointestinal-mediated glucose disposal, Total pancreatectomy, Incretin hormones, Glucagon