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

Completed

• Conditions: Type 2 Diabetes Mellitus
• Interventions: Biological: isoglycemic intravenous glucose infusion and Glucagon infusion, day C; Biological: Oral glucose tolerance test, day A; Biological: intravenous iv glucose infusion, day B

• Registration Number: NCT02010827
• Lead Sponsor: University Hospital, Gentofte, Copenhagen

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.

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 Timeline

• Study Start: 2013-11
• Study First Submitted: 2013-11-27
• Study First Submitted QC: 2013-12-09
• Study First Posted: 2013-12-13
• Primary Completion: 2014-09
• Study Completion: 2015-08
• Status Verified: 2015-11
• Last Update Submitted: 2015-11-30
• Last Update Posted: 2015-12-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
healthy controls	Oral glucose tolerance test, day A	healthy controls
Patients	Oral glucose tolerance test, day A	Patients
healthy controls	isoglycemic intravenous glucose infusion and Glucagon infusion, day C	healthy controls
Patients	isoglycemic intravenous glucose infusion and Glucagon infusion, day C	Patients
Patients	intravenous iv glucose infusion, day B	Patients
healthy controls	intravenous iv glucose infusion, day B	healthy controls

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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 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 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)

Trial Locations

Locations (1)

Diabetes Research Division, University Hospital Gentofte; 🇩🇰 Hellerup, Denmark