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 (iAUC0-180 min) (median (95%CI)) : 215 (156-258) vs. 4 (363-541) mg×L-1×min, P=0.0049) , chylomicron-triglyceride content (iAUC0-270 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. Disclosure L.S.Gasbjerg: Speaker's Bureau; Eli Lilly and Company, Stock/Shareholder; Antag Therapeutics. C.Christoffersen: None. F.K.Knop: Advisory Panel; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk, Sanofi, ShouTi, Zucara Therapeutics, Consultant; AstraZeneca, Eli Lilly and Company, Novo Nordisk, Pharmacosmos A/S, Sanofi, ShouTi, Zealand Pharma A/S, Zucara Therapeutics, Research Support; AstraZeneca, Novo Nordisk, Sanofi, Zealand Pharma A/S, Speaker's Bureau; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Sanofi, Stock/Shareholder; Antag Therapeutics. M.M.Rosenkilde: Research Support; Antag Therapeutics, Bainan Biotech, Stock/Shareholder; Antag Therapeutics, Bainan Biotech, Synklino ApS. M.M.Helsted: None. S.Stensen: Employee; Novo Nordisk A/S. L.S.L.Krogh: None. A.H.Sparre-ulrich: Other Relationship; Antag Therapeutics. B.Hartmann: Board Member; Bainan Biotech. T.Vilsbøll: Consultant; AstraZeneca, Bristol-Myers Squibb Company, Eli Lilly and Company, Gilead Sciences, Inc., GlaxoSmithKline plc., Merck Sharp & Dohme Corp., Mundipharma, Novo Nordisk, Sun Pharmaceutical Industries Ltd. M.B.Christensen: None. J.J.Holst: Advisory Panel; Novo Nordisk, Board Member; Antag Therapeutics, Bainan Biotech. Funding EFSD (no. 94815) ; Novo Nordisk Foundation (no. 13777)