Clinical trial NCT00716170: GIP, GLP-1 and GLP-2 in Type 2 Diabetic Hyperglucagonemia
Official title: The Role of GIP, GLP-1 and GLP-2 in Type 2 Diabetic Hyperglucagonemia
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Type 2 Diabetes Mellitus
Keywords: Diabetes Mellitus
Glucagon
Insulin
Incretin hormones
Glucose-dependent insulinotropic polypeptide
Glucagon-like peptide-1
Glucagon-like peptide-2
Lead sponsor: Herlev Hospital
Sponsor class: OTHER
Collaborators: name: University of Copenhagen
name: The Danish Medical Research Council
name: The Danish Diabetes Association
First posted: 2008-07-16
Enrollment: 10
Sex: ALL
Minimum age (years): 35
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The patients will be recruted from the outpatient clinic of Department of Endocrinology, Herlev Hospital.

Brief summary: In order to investigate the mechanisms underlying the hyperglucagonemia characterizing patients with type 2 diabetes mellitus (T2DM) we wish to test the following hypothesis: Do pancreatic alpha-cells exhibit inappropriate glucagon responses to substances released from the small intestine (GIP, GLP-2 and GLP-2) in patients with T2DM?

Detailed description: Patients with T2DM are not able to suppress their secretion of glucagon after a meal or after oral ingestion of glucose. Patients actually respond with pathological high plasmaglucagon concentrations to these stimuli. Previous studies have shown that postprandial hyperglucagonemia results in increased hepatic glucose production and therefore contributes significantly to the hyperglycemia characterizing these patients.

Recently we have shown that patients with T2DM exhibit a normal suppression of glucagon secretion following an adjustable intravenous (iv) glucose challenge mimicking the glucose excursion following a 50-g oral glucose tolerance test (OGTT) with the latter resulting in lack of glucagon suppression. Why this difference? A possible explanation could be that the oral administration stimulates intestinal factors resulting in a differentially glucagon response to the two similar glucose excursions. We wish to establish whether GIP, GLP-1 and/or GLP-2 are responsible for the inappropriate glucagon suppression following OGTT and meals in patients with T2DM.

Eligibility criteria: Inclusion Criteria:

* Caucasians with diet and/or tablet treated T2DM of at least 3 months duration (diagnosed according to the criterias of the World Health Organization (WHO))
* Normal Hemoglobin
* Prior Informed Consent

Exclusion Criteria:

* Liver disease (ALAT/ASAT \> 2 x upper normal value)
* Diabetic nephropathy (se-creatinin \> 130 um and/or albuminuria
* Treatment with drugs that cannot be discontinued for 12 hours

Primary outcomes:
measure: Plasma glucagon responses
timeFrame: 3 hours
Secondary outcomes:
Other outcomes:
Locations:
city: Herlev
country: Denmark
facility: Department of Endocrinology J, Herlev Hospital
Study officials:
affiliation: Herlev Hospital
name: Tina Vilsbøll, MD DMSc
role: STUDY_CHAIR
affiliation: Gentofte Hospital
name: Filip K Knop, MD PhD
role: STUDY_DIRECTOR
References:
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