1362-P: Endogenous Glucose-Dependent Insulinotropic Polypeptide Facilitates Postprandial Intestinal Lipid Uptake in Healthy Men, but Not in Patients with Type 2 Diabetes

The gut hormone glucose-dependent insulinotropic polypeptide (GIP) stimulates glucose-induced insulin secretion and increases triglyceride deposition in subcutaneous adipose tissue, and these effects are attenuated in both type 2 diabetes (T2D) and obesity. Using the GIP receptor antagonist GIP (3-30) NH₂, we investigated the effect of endogenous GIP on circulating lipoproteins (chylomicrons, VLDL, LDL, HDL) during a meal in healthy men and patients with T2D. We measured apolipoprotein B48 (ApoB48) (as a marker of chylomicron count) and plasma lipoprotein triglyceride and cholesterol content during two liquid meal tests (1,894 kJ) with double-blind infusions of GIP (3-30) NH₂ or placebo (saline) in randomized order in 12 healthy men (19-65 years, BMI 20.3-25.5 kg/m²) and in patients with T2D (44-72 years, HbA1c 6.2-11% (37-70 mmol/mol) , BMI 27.4-41.2 kg/m²) . Compared to placebo, the GIP (3-30) NH₂ infusion lowered postprandial responses of ApoB48 (incremental area under the curve (iAUC_{0-180 min}) (median (95%CI)) : 215 (156-258) vs. 4 (363-541) mg×L^-1×min, P=0.0049) , chylomicron-triglyceride content (iAUC_{0-270 min}: 32.7 (-2.32-72.1) vs. 49.5 (1.21-170) mmol× L^-1×min P=0.083) and HDL-triglyceride content (iAUC0-270min: -0.90 (-1.95-0.18) vs. 0.95 (-0.72-3.95) mmol× L^-1×min, P=0.016) . In patients with T2D, infusion of GIP (3-30) NH₂ did not change postprandial responses of ApoB48 or lipoprotein-triglyceride content. In both groups, there were no differences in lipoprotein-cholesterol contents.