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The Role of Small Intestinal Endocrine Cells in Type 2 Diabetic Hyperglucagonemia (T2DM-PC1-2)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2008 by University Hospital, Gentofte, Copenhagen.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
University Hospital, Gentofte, Copenhagen
ClinicalTrials.gov Identifier:
NCT00639613
First received: March 12, 2008
Last updated: January 12, 2010
Last verified: March 2008
  Purpose

The purpose of this study is to determine whether excessive secretion of glucagon in type 2 diabetes originates from the pancreatic alpha-cells or endocrine cells in the mucosa of the small intestinal.


Condition Intervention
Type 2 Diabetes
Procedure: Double-balloon enteroscopy
Other: Standard meal test

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Exspression of Prohormone Convertase 1 and 2 in Small Intestinal Endocrine Mucosa Cells in Patients With Type 2 Diabetes

Resource links provided by NLM:


Further study details as provided by University Hospital, Gentofte, Copenhagen:

Biospecimen Retention:   Samples With DNA

Buffy coat


Estimated Enrollment: 20
Study Start Date: March 2008
Groups/Cohorts Assigned Interventions
1
Patients with type 2 diabetes
Procedure: Double-balloon enteroscopy
Double-balloon enteroscopy allows for the entire gastrointestinal tract to be visualized in real time. The technique involves the use of a balloon at the end of a special enteroscope camera and an overtube, which is also fitted with a balloon. The procedure is usually done with the use of conscious sedation. The enteroscope and overtube are inserted through the mouth and passed in conventional fashion (that is, as with gastroscopy) into the small bowel. Following this, the endoscope is advanced a small distance in front of the overtube and the balloon at the end is inflated. Using the assistance of friction at the interface of the enteroscope and intestinal wall, the small bowel is accordioned back to the overtube. The overtube balloon is then deployed, and the enteroscope balloon is deflated. The process is then continued until the entire small bowel is visualized. Double-balloon enteroscopy allows for the sampling or biopsying of small bowel mucosa.
Other: Standard meal test
Liquid meal consisting of 100 g "Ny NAN" dissolved in 300 ml water (ca. 5000 kJ) to be ingested over 5 minutes. Blood will be sampled for 4 hours following ingestion. Samples are centrifuges and plasma will be analysed for glucagon, GLP-1, GIP, insulin and C-peptide concentrations.
2
Healthy subjects
Procedure: Double-balloon enteroscopy
Double-balloon enteroscopy allows for the entire gastrointestinal tract to be visualized in real time. The technique involves the use of a balloon at the end of a special enteroscope camera and an overtube, which is also fitted with a balloon. The procedure is usually done with the use of conscious sedation. The enteroscope and overtube are inserted through the mouth and passed in conventional fashion (that is, as with gastroscopy) into the small bowel. Following this, the endoscope is advanced a small distance in front of the overtube and the balloon at the end is inflated. Using the assistance of friction at the interface of the enteroscope and intestinal wall, the small bowel is accordioned back to the overtube. The overtube balloon is then deployed, and the enteroscope balloon is deflated. The process is then continued until the entire small bowel is visualized. Double-balloon enteroscopy allows for the sampling or biopsying of small bowel mucosa.
Other: Standard meal test
Liquid meal consisting of 100 g "Ny NAN" dissolved in 300 ml water (ca. 5000 kJ) to be ingested over 5 minutes. Blood will be sampled for 4 hours following ingestion. Samples are centrifuges and plasma will be analysed for glucagon, GLP-1, GIP, insulin and C-peptide concentrations.

Detailed Description:

Hyperglucagonemia contributes significantly to the hyperglycemia characterizing patients with Type 2 diabetes. Fasting hyperglucagonemia induces hepatic glucose release resulting in elevated fasting levels of plasma glucose. Furthermore, lack of postprandial suppression of glucagon secretion - exchanged for a paradoxical postprandial hypersecretion of glucagon - results in increased levels of postprandial plasma glucose. Additionally, type 2 diabetes is characterized by decreased postprandial responses of the insulinotropic (and glucagonostatic) peptide hormone glucagon-like peptide-1 (GLP-1). Recent studies from our group suggest that the intestines are involved in the diminshed suppression of glucagon following ingestion of nutrients. Thus, suppression of glucagon during oral glucose ingestion diminishes and reverses to stimulation while suppression during intravenous administered glucose sustains along with development of glucose intolerance. In the small intestines mucosal endocrine L-cells secrete GLP-1, which is processed from its precursor, proglucagon, by prohormone convertase 1 (PC1). In the pancreatic alpha-cells proglucagon is processed to glucagon via prohormone convertase 2 (PC2). We plan to examine biopsies from the mucosa of the small intestines from patients with type 2 diabetes and from healthy subjects for glucagon production. Furthermore, the volunteers will be subjected to a standard meal test in order to correlate the gene expression studies with the level of postprandial hyperglucagonemia of the subjects.

  Eligibility

Ages Eligible for Study:   35 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Patients with type 2 diabetes

Criteria

Inclusion Criteria:

  • Diagnosed with type 2 diabetes for at least 3 months
  • Normal hemoglobin
  • Informed consent

Exclusion Criteria:

  • Liver disease (ALAT/ASAT > 2 x normal range)
  • Diabetic nephropathy (se-creatinin > 130 µM and/or albuminuriu)
  • Treatment with medication that can not be stopped for12 hours
  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: NCT00639613

Contacts
Contact: Filip K Knop, MD PhD +45 26 83 01 61 filipknop@dadlnet.dk
Contact: Tina Vilsbøll, MD DMSc + 45 40 94 08 25 t.vilsboll@dadlnet.dk

Locations
Denmark
Department of Internal Medicine F' laboratory Recruiting
Hellerup, Copenhagen County, Denmark, 2900
Principal Investigator: Filip K Knop, MD PhD         
Sponsors and Collaborators
University Hospital, Gentofte, Copenhagen
Investigators
Principal Investigator: Filip K Knop, MD PhD Department of Internal Medicine
  More Information

No publications provided

Responsible Party: Filip K. Knop / MD PhD, Department of Internal Medicine F, Gentofte Hospital, University of Copenhagen
ClinicalTrials.gov Identifier: NCT00639613     History of Changes
Other Study ID Numbers: H-B-2007-031
Study First Received: March 12, 2008
Last Updated: January 12, 2010
Health Authority: Denmark: Danish Dataprotection Agency
Denmark: The Danish National Committee on Biomedical Research Ethics

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on November 27, 2014