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

June 25, 2015 updated by: Filip Krag Knop, University Hospital, Gentofte, Copenhagen

Exspression of Prohormone Convertase 1 and 2 in Small Intestinal Endocrine Mucosa Cells in Patients With Type 2 Diabetes

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
20

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
    • Copenhagen County
      • Hellerup, Copenhagen County, Denmark, 2900
        • Department of Internal Medicine F' laboratory

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

35 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients with type 2 diabetes

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Hospital, Gentofte, Copenhagen

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Filip K Knop, MD PhD, Department of Internal Medicine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2008

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 12, 2008

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 12, 2008

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 20, 2008

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 26, 2015

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 25, 2015

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • H-B-2007-031

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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