Clinical trial NCT00529048: Quantification of the Incretin Effect in Healthy Subjects and Patients With Type 2 Diabetes
Official title: Quantification of the Incretin Effect in Healthy Subjects and Patients With Type 2 Diabetes Using Increasing Amounts of Oral Glucose Challenges
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Incretin Effect
Keywords: Type 2 diabetes mellitus
Incretin effect
Glucagon-Like Peptide 1
Gastric Inhibitory Polypeptide
Lead sponsor: Herlev Hospital
Sponsor class: OTHER
Collaborators: name: University of Copenhagen
name: Merck Sharp & Dohme LLC
name: Forskningsrådet
name: Diabetesforeningen
First posted: 2007-09-14
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The Patients (Cases) will be recruted from the diabetes clinic at Depatment of Endocrinology at Herlev Hospital

The control subjects will be recruted through the lokal papers, and individualy matched by age, sex and BMI to a patient befor enrollment.

Brief summary: Patients with T2DM lac a sufficient incretin response after oral glucose intake. It has only been tested using 50g of glucose. We don't know if patients with T2DM are capable of regulating the incretin effect like healthy people in responds to different amounts of glucose intake.

The aim of the present study is to quantify the incretin effect in healthy subjects and in patients with T2DM during increasing amounts of oral glucose challenges. The proposed studies will answer important questions on the mechanisms underlying T2DM and be of importance in relation to future preventive- and treatment strategies.

Detailed description: The impaired incretin effect in patients with type 2 diabetes mellitus (T2DM) has previously only been evaluated using a glucose load of 50 g, and it is uncertain whether patients with T2DM are capable of regulating their incretin effect equivalent to healthy subjects. Furthermore, it is of great interest to quantify the secretion of GIP and GLP-1 during increasing glucose loads in both patients with T2DM and in healthy subjects in order to evaluate whether an increased secretion of one or both of the two incretin hormones contributes to the regulation of the incretin effect.

The aim of the present study is to quantify the incretin effect in healthy subjects and in patients with T2DM during increasing amounts of oral glucose challenges and corresponding isoglycemic iv glucose challenges. The proposed studies will answer important questions on the pathophysiology underlying T2DM and be of importance in relation to future preventive- and treatment strategies.

Eight patients with T2DM and 8 matched healthy subjects will be evaluated with oral glucose tolerance tests (OGTT) using increasing glucose loads (25, 50 and 100 g glucose) and isoglycemic iv glucose tolerance tests imitating the glucose concentrations as obtained during the oral glucose loads. The results will describe the regulation of the incretin effect in patients with T2DM and, thereby, contribute to the clarification of the pathophysiology of the postprandial hyperglycemia characterizing these patients.

Eligibility criteria: Inclusion Criteria: Cases

* Caucasians with T2DM according to WHO's criteria
* Normal Hemoglobin
* Agree to participate (orally and in writing)
* HbA1c: 6.5-9 %
* BMI: 23-35 kg/m2

Exclusion Criteria:Cases

* Liver disease (ALAT \> 2 x normal level)
* Diabetic nephropathy (s-creatinin \> 130 µM or albuminuria)
* Diabetic neuropathy (anamnestic)
* Proliferative diabetic retinopathy (anamnestic)
* Medical treatment witch cannot be stopped for 12 hours
* Pregnancy or breastfeed
* Treatment with Insulin or glitazones

Inclusion Criteria: Control group

* Caucasians
* Normal oral glucose tolerance according to WHO's criteria
* Normal Hemoglobin
* Agree to participate (orally and in writing)
* BMI: 23-35 kg/m2

Exclusion Criteria: Control group

* Liver disease (ALAT \> 2 x normal level)
* Impaired function of the kidney (s-creatinin \> 130 µM or albuminuria)
* Directly related til to someone suffering from diabetes mellitus
* Medical treatment witch cannot be stopped for 12 hours
* Pregnancy or breastfeed

Primary outcomes:
measure: Progress in Incretin effect in patients with T2DM compared with healthy subjects
timeFrame: 4 hours
Secondary outcomes:
measure: GIP and GLP-1 responscurvs
timeFrame: 4 hours
Other outcomes:
Locations:
city: Herlev
country: Denmark
facility: Endokrinologisk afd. J, Herlev Hospital
state: Region Hovedstaden
Study officials:
affiliation: Herlev Hospital
name: Tina Villsbøll, MD.DMSc.
role: STUDY_CHAIR
affiliation: Herlev Hospital
name: Filip K Knop, MD.Phd.
role: STUDY_DIRECTOR
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citation: Bagger JI, Knop FK, Lund A, Holst JJ, Vilsboll T. Glucagon responses to increasing oral loads of glucose and corresponding isoglycaemic intravenous glucose infusions in patients with type 2 diabetes and healthy individuals. Diabetologia. 2014 Aug;57(8):1720-5. doi: 10.1007/s00125-014-3264-2. Epub 2014 May 31.
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