Type 2 Diabetes Mellitus
Conditions
Keywords
Diabetes mellitus, Glucagon, Endogenous glucose production, Incretin hormones
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.
Interventions
BIOLOGICALisoglycemic intravenous glucose infusion and Glucagon infusion, day C
Infusion of 0.8ng/kg/min glucagon from time 0-25min
BIOLOGICALOral glucose tolerance test, day A
BIOLOGICALintravenous iv glucose infusion, day B
Sponsors
University Hospital, Gentofte, Copenhagen
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
35 Years to 80 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Differences in gastrointestinal hormones during the three days measured as total Area under the curve (tAUC) | At the end of the study | — |
| 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 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) |
Countries
Denmark
Outcome results
None listed