Comparison of Oral Versus Intravenous Glucose Exposure on Plasma Growth Hormone Levels: A Crossover Study in Healthy Volunteers

Background: Hypoglycemia stimulates growth hormone (GH) secretion, whereas hyperglycemia suppresses it. However, the underlying mechanisms are not fully understood, particularly the potential role of gut-derived hormones released in response to oral glucose. Aim: To investigate whether GH suppression is modulated by the route of glucose administration. Methods: A two-day intervention study in healthy volunteers. GH, insulin, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) responses during a 2-hour oral glucose tolerance test (OGTT) were compared with those during a 2-hour isoglycemic intravenous (IV) glucose infusion. GH levels were analyzed using paired T-test of GH concentrations at every blood sample time point. The effect of intervention on all measured hormones were also assessed by paired T-test of Area Under the Curve (AUC). Results: 12 healthy volunteers (6 females, mean age 47.9 ± 5.4 years) were included. In 9 of the 12 subjects, IV glucose induced an early peak in plasma-GH followed by a decrease. At 20 min after glucose intake GH levels increased by 46% during IV glucose compared to a decrease of 17% during oral glucose. The most significant difference in GH between oral vs IV glucose was seen at 45 min (median [range], 0.30 [0.05-1.13] vs. 0.46 [0.05-9.82] µg/l, p=0.072). There was no difference between AUC of GH levels (p=0.381). During IV glucose, two subjects did not reach the threshold for excluding acromegaly. Oral glucose showed significant increases compared to IV glucose for insulin (p<0.001), GLP-1 (p=0.002) and GIP (p<0.001) when using paired T-test of AUC. Conclusions: Route of glucose exposure might influence the suppressive effect of glucose on GH secretion. The potential mechanism behind remains elusive but changes in gut-derived hormones might be of importance.