Elimination of Incretin Hormones in Patients With Severe Kidney Failure

September 18, 2012 updated by: Bo Feldt-Rasmussen

Elimination and Biodegradation of the Incretin Hormones GLP-1 and GIP in Patients With End-stage Renal Disease

The prevalence of type 2 diabetes (T2D) is increasing rapidly worldwide. T2D is characterized by a severely impaired incretin effect. The incretin effect refers to the insulinotropic action of the nutrient-released incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). The incretin effect is defined as the difference in insulin secretory responses between oral and isoglycaemic intravenous glucose challenges (OGTT and IIGI, respectively) and in healthy individuals it accounts for as much as 70% of the insulin response following oral glucose, whereas patients with T2D exhibit an incretin effect in the range of 0 to 30%. Patients with T2D and non-diabetic patients with severe kidney failure share several pathophysiological characteristics, including decreased insulin sensitivity, fasting hyperinsulinaemia and impaired beta-cell function. The reason for these findings remains to be fully elucidated. An ongoing study in our research group is investigating the incretin effect and the incretin hormone secretory responses following OGTT, IIGI and meal ingestion, respectively. In continuation of this study, essential knowledge of metabolism of incretin hormones in an uremic milieu will be obtained in the present study prior to evaluation of the use of incretin-based agents in patients with impaired kidney function. In this second study we evaluate the elimination and biodegradation of GLP-1 and GIP. The biological active incretin hormones are rapidly degraded by the ubiquitous enzyme dipeptidyl peptidase-4 (DPP-4), generating inactive metabolites. The active hormones are however also eliminated by renal clearance, although the importance of this remains questionable. It is likely that the degradation and elimination of the active hormones will be significantly affected in patients with severe kidney impairment.

We hypothesize that elimination and biodegradation of the two incretin hormones, both in it´s active and inactive forms, will be affected in non-diabetic patients with severe kidney failure.

Study Overview

Status

Completed

Conditions

Study Type

Observational

Enrollment (Actual)

24

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

      • Copenhagen, Denmark, 2100
        • Department of Nephrology P, Copenhagen University Hospital, Rigshospitalet

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

Ages Eligible for Study

18 years to 90 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

  1. Hemodialysis patients
  2. Healthy control subjects

Description

1)

Inclusion Criteria:

  • Male or female; aged 18-90 years
  • CKD stage 5 in chronic maintenance dialysis treatment
  • BMI: 18,5-28 kg/m2
  • Normal fasting plasma glucose (<6,1 mM)
  • Normal or impaired glucose tolerance (PG120 min <11,1 mM following OGTT)

Inclusion Criteria:

  • Male or female; aged 18-90 years
  • Healthy including normal kidney function
  • BMI: 18,5-28 kg/m2
  • Normal fasting plasma glucose (<6,1 mM)
  • Normal or impaired glucose tolerance (PG120 min <11,1 mM following OGTT)

1+2)

Exclusion Criteria:

  • Diabetes mellitus
  • Chronic pancreatitis / previous acute pancreatitis
  • Treatment with oral glucocorticoids, calcineurin inhibitors, thiazides, dipeptidyl peptidase 4 (DPP4) inhibitors or other drugs, which could interfere with glucose or lipid metabolism
  • Inflammatory bowel disease
  • Malignant disease
  • Bowel resection
  • Severe anemia (hemoglobin <6.5 mmol/L)

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
Healthy control
Dialysis, Non-diabetic
Hemodialysis

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Intact GLP-1 concentration
Time Frame: -60 min - 180 min
During GLP-1 infusion 0-60 min
-60 min - 180 min
Total GLP-1 concentration
Time Frame: -60 min - 180 min
GLP-1 infusion 0-60 min
-60 min - 180 min
Intact GIP concentration
Time Frame: - 60 min - 180 min
GIP infusion 0-60 min
- 60 min - 180 min
Total GIP infusion
Time Frame: -60 min - 180 min
GIP infusion 0-60 min
-60 min - 180 min

Collaborators and Investigators

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

Publications and helpful links

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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

June 1, 2011

Primary Completion (ACTUAL)

June 1, 2012

Study Completion (ACTUAL)

June 1, 2012

Study Registration Dates

First Submitted

July 11, 2011

First Submitted That Met QC Criteria

July 11, 2011

First Posted (ESTIMATE)

July 12, 2011

Study Record Updates

Last Update Posted (ESTIMATE)

September 19, 2012

Last Update Submitted That Met QC Criteria

September 18, 2012

Last Verified

September 1, 2012

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H-2-2009-158-UREMINC

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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