Abstract

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/m2) 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 (Δbaseline-subtracted area under the curve (bsAUC)C-peptide% ± s.e.m.; -14 ± 6%, P = 0.021) and peak glucagon (Δ% ± 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 (ΔbsAUCCTX; ±s.e.m.; -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, 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.

Original languageEnglish
JournalEuropean Journal of Endocrinology
Volume185
Issue number1
Pages (from-to)33-45
Number of pages13
ISSN0804-4643
DOIs
Publication statusPublished - 21 May 2021

Keywords

  • Adult
  • Aged
  • Blood Glucose/drug effects
  • Bone Resorption/metabolism
  • Collagen Type I/drug effects
  • Cross-Over Studies
  • Diabetes Mellitus, Type 2/metabolism
  • Double-Blind Method
  • Feeding Behavior/drug effects
  • Gastric Inhibitory Polypeptide/metabolism
  • Humans
  • Insulin Secretion/drug effects
  • Male
  • Middle Aged
  • Obesity/metabolism
  • Peptide Fragments/pharmacology
  • Peptides/drug effects
  • Postprandial Period
  • Random Allocation
  • Receptors, Gastrointestinal Hormone/antagonists & inhibitors
  • Subcutaneous Fat/drug effects
  • Triglycerides/metabolism

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