The effect of glucose dynamics on plasma copeptin levels upon glucagon, arginine, and macimorelin stimulation in healthy adults

Abstract Purpose Recently, non-osmotic tests such as glucagon, arginine or macimorelin stimulation were assessed for the ability to evaluated posterior pituitary function. Results showed that glucagon and arginine, but not macimorelin, stimulate copeptin secretion (as a surrogate marker of vasopressin) and, therefore, provide novel tests to assess the posterior pituitary. The exact underlying mechanism behind the stimulatory effect remain elusive.Methods This study combined data from three diagnostic studies conducted at the University Hospital Basel, Switzerland. In total, 80 healthy adults underwent the glucagon (n=22), arginine (n=30), and macimorelin (n= 28) stimulation test. The primary objective was to investigated glucose dynamics upon glucagon, arginine, and macimorelin stimulation tests and its effect on plasma copeptin release.Results Upon glucagon stimulation, the median [IQR] glucose level at baseline was 5.0 [4.6, 5.2] mmol/l, peaked to 8.1 [7.2, 9.4] mmol/l at 30 minutes and decreased to a minimum of 3.8 [3.5, 4.5] mmol/l at 120 minutes. The median copeptin increased upon glucagon stimulation by 7.6 [2.4, 28.0] pmol/l. Upon arginine, the glucose level at baseline was 4.9 [4.8, 5.5] mmol/l, peaked to 6.0 [5.2, 6.4] mmol/l at 30 minutes and decreased to a minimum of 4.3 [3.8, 4.8] mmol/l at 60 minutes. The median copeptin increased upon arginine stimulation by 4.5 [2.9, 7.5] pmol/l. Upon macimorelin, glucose levels showed no notable dynamics over the 120 minutes, and no major change in copeptin was observed. In the pooled dataset, a decrease in glucose levels was significantly correlated with copeptin increase (ρ= 0.49, p<0.001).Conclusion We demonstrate a similar course in plasma glucose after glucagon and arginine stimulation, while macimorelin had no effect on glucose levels, and show a strong correlation between the decrease in glucose levels and increase in copeptin after glucagon and arginine stimulation.