Hyperglycemia Acutely Lowers the Postprandial Excursions of Glucagon-Like Peptide-1 and Gastric Inhibitory Polypeptide in Humans

• Published in: The journal of clinical endocrinology and metabolism Vol. 94; no. 4; pp. 1379 - 1385
• Main Authors: Vollmer, Kirsten, Gardiwal, Husai, Menge, Bjoern A., Goetze, Oliver, Deacon, Carolyn F., Schmidt, Wolfgang E., Holst, Jens J., Meier, Juris J.
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Oxford University Press 01.04.2009; Endocrine Society
• Subjects: Adult; Biological and medical sciences; Body Mass Index; C-Peptide - blood; Cholesterol, HDL - blood; Diabetes; Diabetes mellitus (non-insulin dependent); Endocrinopathies; Experiments; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Gastric Emptying; Gastric Inhibitory Polypeptide - blood; Glucagon; Glucagon - blood; Glucagon-like peptide 1; Glucagon-Like Peptide 1 - blood; Glucose; Glucose Clamp Technique; Humans; Hyperglycemia; Hyperglycemia - blood; Hyperglycemia - physiopathology; Insulin; Kidney Function Tests; Liver Function Tests; Male; Medical sciences; Peptides; Polypeptides; Postprandial Period; Reference Values; Triglycerides; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology; Young Adult; Human; Obesity; Hyperglycemia; Gastrointestinal hormone; Nutrition; Postprandial; Nutrition disorder; Metabolic diseases; Gastric inhibitory peptide; Endocrinology; Nutritional status; Glucagon like peptide 1
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/jc.2008-2197

Introduction: 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. Patients and 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 13C-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.