Elimination of Incretin Hormones in Patients With Severe Kidney Failure

NCT01391884 | Completed DMC

• 1 other identifier: H-2-2009-158-UREMINC
• Study Type: observational
• Target: 24
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (4)

• Intact GLP-1 concentration

  During GLP-1 infusion 0-60 min

  -60 min - 180 min

• Total GLP-1 concentration

  GLP-1 infusion 0-60 min

  -60 min - 180 min

• Intact GIP concentration

  GIP infusion 0-60 min

  - 60 min - 180 min

• Total GIP infusion

  GIP infusion 0-60 min

  -60 min - 180 min

Study Arms (2)

Dialysis, Non-diabetic

Hemodialysis

Healthy control

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

1. Hemodialysis patients 2. Healthy control subjects

You may qualify if:

• 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)
• +2)

You may not qualify if:

• 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)

Sponsors & Collaborators

• Bo Feldt-Rasmussen: lead

Study Sites (1)

Department of Nephrology P, Copenhagen University Hospital, Rigshospitalet

Copenhagen, Copenhagen, 2100, Denmark

Location

Related Publications (1)

• 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.

  PMID: 24712563 DERIVED

MeSH Terms

Conditions

Uremia

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD DMSc

Study Record Dates

• First Submitted: July 11, 2011
• First Posted: July 12, 2011
• Study Start: June 1, 2011
• Primary Completion: June 1, 2012
• Study Completion: June 1, 2012
• Last Updated: September 19, 2012

Record last verified: 2012-09

Locations

DK (1)