Elimination of Incretin Hormones in Patients With Severe Kidney Failure

NCT ID: NCT01391884

Last Updated: 2012-09-19

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 24 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2011-06-30
• Study Completion Date: 2012-06-30

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.

Conditions

Uremia

Keywords

Incretin hormones; GLP-1; GIP; Uremia; Dialysis

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

Dialysis, Non-diabetic

Hemodialysis

No interventions assigned to this group

Healthy control

No interventions assigned to this group

Eligibility Criteria

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)

• 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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Bo Feldt-Rasmussen

OTHER

Sponsor Role: lead

Responsible Party

Bo Feldt-Rasmussen

MD DMSc

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

Department of Nephrology P, Copenhagen University Hospital, Rigshospitalet

Copenhagen, Copenhagen, Denmark

Countries

Denmark

References

Idorn T, Knop FK, Jorgensen MB, Christensen M, Holst JJ, Hornum M, Feldt-Rasmussen B. Elimination and degradation of glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide in patients with end-stage renal disease. J Clin Endocrinol Metab. 2014 Jul;99(7):2457-66. doi: 10.1210/jc.2013-3809. Epub 2014 Apr 8.

Reference Type: DERIVED

PMID: 24712563 (View on PubMed)

Other Identifiers

H-2-2009-158-UREMINC

Identifier Type: -

Identifier Source: org_study_id