Hyperglycemia acutely lowers the postprandial excursions of glucagon-like Peptide-1 and gastric inhibitory polypeptide in humans.
BACKGROUND
Impaired secretion of glucagon-like peptide 1 (GLP-1) has been suggested to contribute to the deficient incretin effect in patients with type 2 diabetes. It is unclear whether this is a primary defect or a consequence of the hyperglycemia in type 2 diabetes. We examined whether acute hyperglycemia reduces the postprandial excursions of gastric inhibitory polypeptide (GIP) and GLP-1, and if so, whether this can be attributed to changes in gastric emptying.


METHODS
Fifteen nondiabetic individuals participated in a euglycemic clamp and a hyperglycemic clamp experiment, carried out over 285 min. A mixed meal was ingested after 45 min. Plasma concentrations of glucose, insulin, C-peptide, glucagon, triglycerides, GIP, and GLP-1 were determined, and gastric emptying was assessed using a (13)C-octanoate breath test.


RESULTS
Glucose levels were 160 +/- 1 mg/dl during the hyperglycemic clamp experiments and 83 +/- 3 mg/dl during the euglycemia (P < 0.0001). Glucose infusion rates were higher during hyperglycemia, but meal ingestion led to a decline in glucose requirements in both experiments (P < 0.0001). Insulin and C-peptide levels were higher during the hyperglycemic clamp experiments (P < 0.0001), whereas glucagon levels were higher during euglycemia (P < 0.0001). The postprandial increases in GIP and GLP-1 concentrations were 46 and 52% lower during the experiments with hyperglycemia (P = 0.0017 and P = 0.021). Hyperglycemia also elicited a significant delay in gastric emptying (P < 0.0001).


CONCLUSIONS
Hyperglycemia acutely reduces the postprandial levels of GIP and GLP-1, possibly through a deceleration of gastric emptying. This supports the concept that reduced incretin levels in some patients with type 2 diabetes are a consequence rather than a cause of type 2 diabetes.
Vollmer
Kirsten
K
Department of Medicine I, St Josef-Hospital , Ruhr-University Bochum, Bochum, Germany.
Gardiwal
Husai
H
Menge
Bjoern A
BA
Goetze
Oliver
O
Deacon
Carolyn F
CF
Schmidt
Wolfgang E
WE
Holst
Jens J
JJ
Meier
Juris J
JJ
D000328:Adult; D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D005260:Female; D005746:Gastric Emptying; D005749:Gastric Inhibitory Polypeptide / Q000097:blood*; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000097:blood*; D015309:Glucose Clamp Technique; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000503:physiopathology*; D007677:Kidney Function Tests; D008111:Liver Function Tests; D008297:Male; D019518:Postprandial Period; D012016:Reference Values; D055815:Young Adult
D002096:C-Peptide; D008076:Cholesterol, HDL; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D005934:Glucagon