Clinical trial NCT02010827: Endogenous Glucoseproduction in Patients With Type 2 Diabetes Mellitus During Oral Glucose and iv. Glucose Infusion
Official title: Endogenous Glucoseproduction in Patients With Type 2 Diabetes Mellitus During Oral Glucose and iv. Glucose Infusion
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Type 2 Diabetes Mellitus
Keywords: Diabetes mellitus
Glucagon
Endogenous glucose production
Incretin hormones
Lead sponsor: University Hospital, Gentofte, Copenhagen
Sponsor class: OTHER
First posted: 2013-12-13
Enrollment: 20
Sex: ALL
Minimum age (years): 35
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with type 2 diabetes Healthy control subjects

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.

Eligibility criteria: 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

Primary outcomes:
measure: Differences in Endogenous glucose production during the three days measured as total Area under the curve (tAUC)
timeFrame: 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 outcomes:
measure: Differences in glucagon during the three days measured as total Area under the curve (tAUC)
timeFrame: 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.
measure: Differences in incretin hormone levels during the three days measured as total Area under the curve (tAUC)
timeFrame: 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.
measure: Differences in gastrointestinal hormones during the three days measured as total Area under the curve (tAUC)
timeFrame: At the end of the study
measure: differences in appetite, hunger, satiety between the three days
timeFrame: Satiety, hunger and appetite will be measured at time points:0,30,60,90,120,150,180, 240 min during each day.
Other outcomes:
Locations:
city: Hellerup
country: Denmark
facility: Diabetes Research Division, University Hospital Gentofte
Study officials:
References:
citation: Lund A, Bagger JI, Christensen M, Grondahl M, van Hall G, Holst JJ, Vilsboll T, Knop FK. Higher Endogenous Glucose Production During OGTT vs Isoglycemic Intravenous Glucose Infusion. J Clin Endocrinol Metab. 2016 Nov;101(11):4377-4384. doi: 10.1210/jc.2016-1948. Epub 2016 Aug 17.