The Effect of the Incretin Hormones on the Endocrine Pancreatic Function During Hyperglycemia in End-stage Renal Disease

NCT ID: NCT02237521

Last Updated: 2017-05-22

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 24 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2014-09-30
• Study Completion Date: 2016-04-28

Brief Summary

Patients with end-stage renal disease (ESRD) have a high prevalence of impaired glucose metabolism. The pathophysiological cause is uncertain, but disturbances in the secretion, elimination and effect of glucagon, insulin and the two incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), probably play important roles. Our research group has previously found that dialysis patients without type 2 diabetes mellitus (T2DM) have a reduced incretin effect and an inability to suppress glucagon after a meal - two early pathophysiological characteristics of patients with T2DM and normal kidney function.

The aim of the project is to provide a detailed description of the mechanisms underlying the (patho)physiological effects of the incretin hormones in patients with ESRD. We plan to investigate the above mentioned disturbances during fasting and hyperglycaemic conditions using incretin infusions during glucose clamping. Furthermore, stable isotopic tracers will be used to determine the effect of the incretin hormones on the endogenous glucose handling.

We hypothesise that the effects of the incretin hormones in ESRD will be reduced in respect to healthy control subjects.

Detailed Description

The effect of the incretin hormones on the endocrine pancreatic function in a uremic environment will be explored during fasting and hyperglycemic conditions in three randomised examination days.

At a preceding screening day, an oral glucose tolerance test (OGTT) and a dual energy x-ray absorptiometry (DXA) scan will be performed to determine glucose tolerance and the distribution of muscle and adipose tissue. The study will be carried out on three separate days differing with respect to the hormones infused: GLP-1, GIP or placebo (saline) which are double blinded. The patients will meet from an overnight fast and an infusion of one of the hormones is initiated. At the same time labeled glucose will be infused to determine the endogenous hepatic glucose production. A glucose infusion is adjusted according to frequent plasma glucose measurements to maintain fasting glucose level. After 2 hours a steady state of the tracer is achieved and a 2 hour hyperglycemic clamp, 3 mmol/l above fasting glucose concentration will be started. The tracer infusions are continued during the hyperglycemia. After the 4 hour clamp an arginine bolus will be administered to measure the ability to increase the secretion of insulin and glucagon.

Conditions

End-stage Renal Disease

Study Design

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

Study Groups

End-stage renal disease

Patients with normal glucose tolerance and end-stage renal disease

Eu- and hyperglycemic clamp

Intervention Type: OTHER

Eu- and hyperglycemic clamp with concomitant infusion of the natural occurring hormones glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP) or placebo along with stable glucose isotope infusion to measure the effects of the incretins.

Arginine test

Intervention Type: OTHER

Bolus infusion of the natural occurring amino acid arginine to measure the ability to increase the secretion of insulin and glucagon

Controls

Healthy controls with normal kidney function and normal glucose tolerance

Eu- and hyperglycemic clamp

Intervention Type: OTHER

Eu- and hyperglycemic clamp with concomitant infusion of the natural occurring hormones glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP) or placebo along with stable glucose isotope infusion to measure the effects of the incretins.

Arginine test

Intervention Type: OTHER

Bolus infusion of the natural occurring amino acid arginine to measure the ability to increase the secretion of insulin and glucagon

Interventions

Eu- and hyperglycemic clamp

Eu- and hyperglycemic clamp with concomitant infusion of the natural occurring hormones glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP) or placebo along with stable glucose isotope infusion to measure the effects of the incretins.

Intervention Type: OTHER

Arginine test

Bolus infusion of the natural occurring amino acid arginine to measure the ability to increase the secretion of insulin and glucagon

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Chronic hemodialysis-dependent uremia in more than 3 months

• Normal kidney function

Exclusion Criteria

• Fasting plasma glucose ≥ 6.1 mmol/l
• 2h plasma glucose ≥ 7.8 after ingestion of 75 grams of glucose
• Admittance to a hospital
• Anemia (Hb < 6.0 mmol/l)
• Ongoing treatment with drugs interfering with glucose metabolism including steroids and calcineurin inhibitors
• Bowel resection or any other large abdominal surgery

• 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

Principal Investigators

Morten B Jørgensen, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Nephrology, Rigshospitalet

Locations

Department of Nephrology, Rigshospitalet

Copenhagen, , Denmark

Countries

Denmark

Other Identifiers

H-2-2014-021

Identifier Type: -

Identifier Source: org_study_id