Glucose-dependent insulinotropic polypeptide reduces postprandial glucose excursions but does not protect from hypoglycaemia in persons with type 1 diabetes-A randomised placebo-controlled study.

AIMS: 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.

MATERIALS AND

METHODS

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).

RESULTS

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.

CONCLUSION

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.