Effects Of Endogenous Gip In Patients With Type 2 Diabetes

Objective: The insulinotropic effect of exogenous, intravenously infused glucose-dependent insulinotropic polypeptide (GIP) is impaired in patients with type 2 diabetes. We evaluated the effects of endogenous GIP in relation to glucose and bone metabolism in patients with type 2 diabetes using a selective GIP receptor antagonist and hypothesized that the effects of endogenous GIP were preserved.Design: A randomized, double-blinded, placebo-controlled, crossover study.Methods: Ten patients with overweight/obesity and type 2 diabetes (mean +/- s.D.; HbA1c 52 +/- 11 mmol/mol; BMI 32.5 +/- 4.8 kg/m(2)) were included. We infused a selective GIP receptor antagonist, GIP(3-30)NH2 (1200 pmol/kg/min), or placebo (saline) during two separate, 230-min, standardized, liquid mixed meal tests followed by a meal ad libitum. Subcutaneous adipose tissue biopsies were analyzed.Results: Compared with placebo, GIP(3-30)NH2 reduced postprandial insulin secretion (Delta baseline-subtracted area under the curve (bsAUC)C-peptide% +/- s.E.M.; -14 +/- 6%, P = 0.021) and peak glucagon (Delta% +/- s.E.M.; -11 +/- 6%, P = 0.046) but had no effect on plasma glucose (P = 0.692). Suppression of bone resorption (assessed by circulating carboxy-terminal collagen crosslinks (CTX)) was impaired during GIP(3-30)NH2 infusion compared with placebo (Delta bsAUCCTX; +/- s.E.M.; -4.9 +/- 2 ng/mL x min, P = 0.005) corresponding to a similar to 50% reduction. Compared with placebo, GIP(3-30)NH2 did not affect plasma lipids, meal consumption ad libitum or adipose tissue triglyceride content.Conclusions: Using a selective GIP receptor antagonist during a meal, we show that endogenous GIP increases postprandial insulin secretion with little effect on postprandial glycaemia but is important for postprandial bone homeostasis in patients with type 2 diabetes.