The Effect of the Incretin Hormones on the Endocrine Pancreatic Function During Hyperglycemia in End-stage Renal Disease
Condition: End-stage Renal Disease
MeSH terms: Kidney Diseases; Kidney Failure, Chronic
Study type: Observational

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.
    

Intervention name(s): Eu- and hyperglycemic clamp; Arginine test
Intervention type(s): Other; Other
Intervention description(s): 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.; Bolus infusion of the natural occurring amino acid arginine to measure the ability to increase the secretion of insulin and glucagon
Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        1. End-stage renal disease patients receiving chronic hemodialysis treatments

          2. Healthy control subjects
      
Biospecimen description: 
      Serum, plasma and urine
    
Keywords: Incretin hormones; End-stage renal disease; ESRD; GLP-1; GIP; Insulin; Glucagon