Effects of endogenous GIP in patients with type 2 diabetes

in European Journal of Endocrinology
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  • 1 S Stensen, Center for Clinical Metabolic Reserach , Gentofte University Hospital, Hellerup, Denmark
  • 2 L Gasbjerg, Center for Clinical Metabolic Reserach , Gentofte University Hospital, Hellerup, Denmark
  • 3 L Krogh, Center for Clinical Metabolic Research, Gentofte University Hospital, Hellerup, Denmark
  • 4 K Skov-Jeppesen, Department of Biomedical Sciences, University of Copenhagen, Kobenhavn, Denmark
  • 5 A Sparre-Ulrich, Department of Biomedical Sciences, University of Copenhagen, Kobenhavn, Denmark
  • 6 M Jensen, Department of Biomedical Sciences, University of Copenhagen, Kobenhavn, Denmark
  • 7 F Dela, Department of Geriatrics, Bispebjerg Hospital, Kobenhavn, Denmark
  • 8 B Hartmann, Department of Biomedical Science, University of Copenhagen, Kobenhavn, Denmark
  • 9 T Vilsbøll, Center for Clinical Metabolic Research, Gentofte University Hospital, DK-2900 Hellerup, Denmark
  • 10 J Holst, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
  • 11 M Rosenkilde, Department of Biomedical Sciences, University of Copenhagen, Kobenhavn, Denmark
  • 12 M Christensen, Center for Clinical Metabolic Research, Gentofte University Hospital, Hellerup, Denmark
  • 13 F Knop, Center for Clinical Metabolic Research, Gentofte University Hospital, Hellerup, Denmark

Correspondence: Filip Knop, Email: filipknop@dadlnet.dk

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±SD; HbA1c 52±11 mmol/mol; BMI 32.5±4.8 kg/m2) were included. We infused a selective GIP receptor antagonist, GIP(3-30)NH2 (1,200 pmol × kg-1 × min-1), or placebo (saline) during two separate, 230-minute, standardized, liquid mixed meal tests followed by an ad libitum meal. Subcutaneous adipose tissue biopsies were analyzed.

Results: Compared with placebo, GIP(3-30)NH2 reduced postprandial insulin secretion (Δbaseline-subtracted area under the curve (bsAUC)C-peptide%±SEM; -14±6%, p=0.021) and peak glucagon (Δ%±SEM; -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 (ΔbsAUCCTX;±SEM; -4.9±2 ng/ml × min, p=0.005) corresponding to a ~50% reduction. Compared with placebo, GIP(3-30)NH2 did not affect plasma lipids, ad libitum meal consumption 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 glycemia but is important for postprandial bone homeostasis in patients with type 2 diabetes.