Endogenous Glucoseproduction in Patients With Type 2 Diabetes Mellitus During Oral Glucose and iv. Glucose Infusion

Study Overview
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Brief Summary
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We want to investigate how lack of glucagon suppression during an oral glucose tolerance test in patients with type 2 diabetes contributes to patients postprandial hyperglycemia.

Detailed Description
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Patients with type 2 diabetes mellitus (T2DM) are not able to suppress their glucagon secretion after a meal or after ingestion of glucose. Previous studies have shown that gastrointestinal hormones might play a role in this phenomenon. However, it has not yet been possible to determine whether this lack of glucagon suppression postprandially results in an increased endogenous glucose secretion, and thus is a factor in the patients postprandial hyperglycemia. We aim to perform oral glucose tolerance tests and isoglycemic intravenous glucose infusions with and without a continuous glucagon infusion in patients with T2DM and healthy control subjects. The glucagon infusion is aiming at copying the inappropriate physiological glucagon response observed in patients with T2DM.

Official Title
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Endogenous Glucoseproduction in Patients With Type 2 Diabetes Mellitus During Oral Glucose and iv. Glucose Infusion

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Biological: isoglycemic intravenous glucose infusion and Glucagon infusion, day C
* Biological: Oral glucose tolerance test, day A
* Biological: intravenous iv glucose infusion, day B


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with T2DM Caucasions above 35 years of age with diet and/or tablettreated T2DM of at -least three months (diagnosis acording to WHO) 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 35 years Informed consent Exclusion Criteria: Inflammatory bowel disease 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 Patients with T2DM 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: 35 Years
Maximum Age: 80 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 |
| --- | --- |
| Patients<br>Patients | Biological: isoglycemic intravenous glucose infusion and Glucagon infusion, day C<br>* Infusion of 0.8ng/kg/min glucagon from time 0-25min<br>Biological: Oral glucose tolerance test, day A<br> <br> Biological: intravenous iv glucose infusion, day B<br> <br> |
| healthy controls<br>healthy controls | Biological: isoglycemic intravenous glucose infusion and Glucagon infusion, day C<br>* Infusion of 0.8ng/kg/min glucagon from time 0-25min<br>Biological: Oral glucose tolerance test, day A<br> <br> Biological: intravenous iv glucose infusion, day B<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences in Endogenous glucose production during the three days measured as total Area under the curve (tAUC) | 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 and 240 min on all days. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences in glucagon during the three days measured as total Area under the curve (tAUC) |  | Glucagon will be measured at time points: -30,-15,0,10,20,30,50,70,90,120,150,180 and 240 min on all days. | 
| Differences in incretin hormone levels during the three days measured as total Area under the curve (tAUC) | GIP and GLP-1 | incretin hormone levels will be measured at time points: -30,-15,0,10,20,30,50,70,90,120,150,180, 240 min on all days. | 
| Differences in gastrointestinal hormones during the three days measured as total Area under the curve (tAUC) |  | At the end of the study | 
| differences in appetite, hunger, satiety between the three days | 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, 240 min during each day. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes mellitus, Glucagon, Endogenous glucose production, Incretin hormones