Quantification of the Incretin Effect in Healthy Subjects and Patients With Type 2 Diabetes

This study has been completed.
Sponsor:
Collaborators:
University of Copenhagen
Merck Sharp & Dohme Corp.
Forskningsrådet
Diabetesforeningen
Information provided by:
Herlev Hospital
ClinicalTrials.gov Identifier:
NCT00529048
First received: September 12, 2007
Last updated: October 19, 2009
Last verified: October 2009
  Purpose

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.


Condition Intervention
Incretin Effect
Other: Oral Glucose Tolerance Test
Other: Isoglycemic clamp
Other: Gastric emptying rate

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Cross-Sectional
Official Title: Quantification of the Incretin Effect in Healthy Subjects and Patients With Type 2 Diabetes Using Increasing Amounts of Oral Glucose Challenges

Resource links provided by NLM:


Further study details as provided by Herlev Hospital:

Primary Outcome Measures:
  • Progress in Incretin effect in patients with T2DM compared with healthy subjects [ Time Frame: 4 hours ]

Secondary Outcome Measures:
  • GIP and GLP-1 responscurvs [ Time Frame: 4 hours ]

Biospecimen Retention:   Samples With DNA

p-Glucose p-Glucagon p-insulin p-c-pep. p-GLP-1 p-GIP Buffy coat s-paracetamol


Enrollment: 16
Study Start Date: October 2007
Study Completion Date: September 2009
Groups/Cohorts Assigned Interventions
T2DM
T2DM patients (WHO-criteria)
Other: Oral Glucose Tolerance Test
The test is preformed 3 times with 3 different amounts of glucose (25g, 75g and 125g) deluded in 300ml of water.
Other: Isoglycemic clamp
I.v. glucose infusion initiating the glucose responds curves from the OGTT
Other: Gastric emptying rate
Paracetamol absorption test. Intake of 1,5g of paracetamol followed by measuring the absorption curve
CTRL
Healthy control subjects matched individually to the cases.
Other: Oral Glucose Tolerance Test
The test is preformed 3 times with 3 different amounts of glucose (25g, 75g and 125g) deluded in 300ml of water.
Other: Isoglycemic clamp
I.v. glucose infusion initiating the glucose responds curves from the OGTT
Other: Gastric emptying rate
Paracetamol absorption test. Intake of 1,5g of paracetamol followed by measuring the absorption curve

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00529048

Locations
Denmark
Endokrinologisk afd. J, Herlev Hospital
Herlev, Region Hovedstaden, Denmark, 2730
Sponsors and Collaborators
Herlev Hospital
University of Copenhagen
Merck Sharp & Dohme Corp.
Forskningsrådet
Diabetesforeningen
Investigators
Study Chair: Tina Villsbøll, MD.DMSc. Herlev Hospital
Study Director: Filip K Knop, MD.Phd. Herlev Hospital
  More Information

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Jonatan Bagger, University of Copehagen
ClinicalTrials.gov Identifier: NCT00529048     History of Changes
Other Study ID Numbers: INK-GLUKOSE1
Study First Received: September 12, 2007
Last Updated: October 19, 2009
Health Authority: Denmark: National Board of Health
Denmark: The Danish National Committee on Biomedical Research Ethics
Denmark: The Ministry of the Interior and Health

Keywords provided by Herlev Hospital:
Type 2 diabetes mellitus
Incretin effect
Glucagon-Like Peptide 1
Gastric Inhibitory Polypeptide

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Gastric Inhibitory Polypeptide
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Gastrointestinal Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 28, 2014