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

Sponsor

University Hospital, Gentofte, Copenhagen (Other)

Overall Status

Completed

CT.gov ID

NCT02010827

Collaborator

(none)

Enrollment

Location

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Mellitus	Biological: isoglycemic intravenous glucose infusion and Glucagon infusion, day C Biological: Oral glucose tolerance test, day A Biological: intravenous iv glucose infusion, day B

Detailed Description

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.

Study Design

Study Type:

Observational

Actual Enrollment :

20 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

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

Study Start Date :

Nov 1, 2013

Actual Primary Completion Date :

Sep 1, 2014

Actual Study Completion Date :

Aug 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Patients Patients	Biological: isoglycemic intravenous glucose infusion and Glucagon infusion, day C Infusion of 0.8ng/kg/min glucagon from time 0-25min Biological: Oral glucose tolerance test, day A Biological: intravenous iv glucose infusion, day B
healthy controls healthy controls	Biological: isoglycemic intravenous glucose infusion and Glucagon infusion, day C Infusion of 0.8ng/kg/min glucagon from time 0-25min Biological: Oral glucose tolerance test, day A Biological: intravenous iv glucose infusion, day B

Arm

Intervention/Treatment

Patients

Biological: isoglycemic intravenous glucose infusion and Glucagon infusion, day C

Infusion of 0.8ng/kg/min glucagon from time 0-25min

Biological: Oral glucose tolerance test, day A

Biological: intravenous iv glucose infusion, day B

healthy controls

Biological: isoglycemic intravenous glucose infusion and Glucagon infusion, day C

Infusion of 0.8ng/kg/min glucagon from time 0-25min

Biological: Oral glucose tolerance test, day A

Biological: intravenous iv glucose infusion, day B

Outcome Measures

Primary Outcome Measures

Differences in Endogenous glucose production during the three days measured as total Area under the curve (tAUC) [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.]
calculated based on infusions of stable isotope marked glucose

Secondary Outcome Measures

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) [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.]
GIP and GLP-1
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 [Satiety, hunger and appetite will be measured at time points:0,30,60,90,120,150,180, 240 min during each day.]
Will be measured with visual analogue scales (VAS)

Eligibility Criteria

Criteria

Ages Eligible for Study:

35 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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