Elimination of Incretin Hormones in Patients With Severe Kidney Failure

Sponsor

Bo Feldt-Rasmussen (Other)

Overall Status

Completed

CT.gov ID

NCT01391884

Collaborator

(none)

Enrollment

Location

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Uremia

Study Design

Study Type:

Observational

Actual Enrollment :

24 participants

Observational Model:

Case-Control

Time Perspective:

Cross-Sectional

Official Title:

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

Study Start Date :

Jun 1, 2011

Actual Primary Completion Date :

Jun 1, 2012

Actual Study Completion Date :

Jun 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Dialysis, Non-diabetic Hemodialysis
Healthy control

Outcome Measures

Primary Outcome Measures

Intact GLP-1 concentration [-60 min - 180 min]
During GLP-1 infusion 0-60 min
Total GLP-1 concentration [-60 min - 180 min]
GLP-1 infusion 0-60 min
Intact GIP concentration [- 60 min - 180 min]
GIP infusion 0-60 min
Total GIP infusion [-60 min - 180 min]
GIP infusion 0-60 min

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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)