Glucose-dependent insulinotropic polypeptide reduces postprandial glucose excursions but does not protect from...

In type 1 diabetes, glucose-dependent insulinotropic polypeptide (GIP) increases glucagon secretion during low plasma glucose and improves time in the glycaemic range during daytime. To explore the glucose-stabilising potential of GIP in type 1 diabetes, we evaluated the effects of exogenous and endogenous GIP on plasma glucose excursions in a setting of excess prandial insulin and physical activity after meal ingestion.

In a randomised, placebo-controlled, double-blind crossover design, 12 men with type 1 diabetes underwent three separate study days involving a 4.5-h continuous intravenous infusion of GIP, the GIP receptor antagonist GIP(3-30)NH₂, and placebo, respectively, during which ingestion of a standardised mixed meal with subcutaneous injection of excess prandial insulin (125% of normal dose) was followed by 30 min of intermediate resistance bicycling (to increase the risk of postprandial hypoglycaemia).

The GIP infusion did not protect against hypoglycaemia, but compared to GIP(3-30)NH₂ infusion, it attenuated postprandial maximum plasma glucose by 1.5 ± 0.5 mmol/L (mean ± standard error of the mean) (p = 0.048). GIP(3-30)NH₂ did not exacerbate glucose excursions or risk of hypoglycaemia compared with placebo. The amount of glucose infused to avoid plasma glucose <2.5 mmol/L was similar on all three study days. No differences were found in C-peptide, insulin or glucagon levels.

GIP did not prevent hypoglycaemia following excess prandial insulin and physical activity after meal ingestion in males with type 1 diabetes, but it reduced peak postprandial plasma glucose compared to GIP(3-30)NH₂.