Postprandial responses of incretin and pancreatic hormones in non-diabetic patients with end-stage renal disease.
BACKGROUND
Patients with end-stage renal disease (ESRD) have glucometabolic disturbances resulting in a high prevalence of prediabetes. The underlying pathophysiology remains unclear, but may prove important for the strategies employed to prevent progression to overt diabetes. Meal-induced release of the insulinotropic gut-derived incretin hormones and pancreatic hormones play a critical role in the maintenance of a normal postprandial glucose tolerance.


METHODS
We studied patients with ESRD and either normal (n = 10) or impaired (n = 10) glucose tolerance, and control subjects (n = 11). Plasma concentrations of glucose, insulin, glucagon, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and paracetamol were measured repeatedly during a standardized 4-h liquid meal including 1.5 g paracetamol (added for evaluation of gastric emptying).


RESULTS
Fasting glucose and postprandial glucose responses were comparable between groups (P > 0.082). Patients with ESRD exhibited higher fasting levels of GIP and glucagon compared with controls (P < 0.001). Baseline-corrected GLP-1 and glucagon responses were enhanced (P < 0.002), baseline-corrected insulin responses and insulin excursions were reduced (P < 0.035), and paracetamol excursions were delayed (P < 0.024) in patients with ESRD compared with controls. None of the variables differed between the two ESRD subgroups.


CONCLUSIONS
Non-diabetic patients with ESRD were characterized by reduced postprandial insulin responses despite increased secretion of the insulinotropic incretin hormone GLP-1. Fasting levels and baseline-corrected responses of glucagon were elevated and gastric emptying was delayed in the ESRD patients. These perturbations seem to be caused by uraemia per se and may contribute to the disturbed glucose metabolism in ESRD patients.
Department of Nephrology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Thomas
T
Idorn
Filip K
FK
Knop
Morten
M
Jørgensen
Jens J
JJ
Holst
Mads
M
Hornum
Bo
B
Feldt-Rasmussen
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D005260:Female; D005746:Gastric Emptying / Q000502:physiology; D005749:Gastric Inhibitory Polypeptide / Q000097:blood; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D006801:Humans; D054795:Incretins / Q000097:blood*; D007328:Insulin / Q000097:blood; D007676:Kidney Failure, Chronic / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010187:Pancreatic Hormones / Q000097:blood*; D019518:Postprandial Period / Q000502:physiology*
D001786:Blood Glucose; D054795:Incretins; D007328:Insulin; D010187:Pancreatic Hormones; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D005934:Glucagon
end-stage renal disease (ESRD); glucagon; glucagon-like peptide-1 (GLP-1); glucose-dependent insulinotropic polypeptide (GIP); incretin hormones; meal test