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Effects of endogenous GIP in patients with type 2 diabetes

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Stensen, Signe ; Gasbjerg, Lærke S ; Krogh, Liva L ; Skov-Jeppesen, Kirsa ; Sparre-Ulrich, Alexander H ; Jensen, Mette H ; Dela, Flemming ; Hartmann, Bolette ; Vilsbøll, Tina ; Holst, Jens J ; Rosenkilde, Mette M ; Christensen, Mikkel B ; Knop, Filip K. / Effects of endogenous GIP in patients with type 2 diabetes. In: European Journal of Endocrinology. 2021 ; Vol. 185, No. 1. pp. 33-45.

Bibtex

@article{787bcbcf5ba544e7bba2661076df59ca,
title = "Effects of endogenous GIP in patients with type 2 diabetes",
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.",
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",
author = "Signe Stensen and Gasbjerg, {L{\ae}rke S} and Krogh, {Liva L} and Kirsa Skov-Jeppesen and Sparre-Ulrich, {Alexander H} and Jensen, {Mette H} and Flemming Dela and Bolette Hartmann and Tina Vilsb{\o}ll and Holst, {Jens J} and Rosenkilde, {Mette M} and Christensen, {Mikkel B} and Knop, {Filip K}",
year = "2021",
month = may,
day = "21",
doi = "10.1530/EJE-21-0135",
language = "English",
volume = "185",
pages = "33--45",
journal = "European Journal of Endocrinology",
issn = "0804-4643",
publisher = "BioScientifica Ltd.",
number = "1",

}

RIS

TY - JOUR

T1 - Effects of endogenous GIP in patients with type 2 diabetes

AU - Stensen, Signe

AU - Gasbjerg, Lærke S

AU - Krogh, Liva L

AU - Skov-Jeppesen, Kirsa

AU - Sparre-Ulrich, Alexander H

AU - Jensen, Mette H

AU - Dela, Flemming

AU - Hartmann, Bolette

AU - Vilsbøll, Tina

AU - Holst, Jens J

AU - Rosenkilde, Mette M

AU - Christensen, Mikkel B

AU - Knop, Filip K

PY - 2021/5/21

Y1 - 2021/5/21

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Blood Glucose/drug effects

KW - Bone Resorption/metabolism

KW - Collagen Type I/drug effects

KW - Cross-Over Studies

KW - Diabetes Mellitus, Type 2/metabolism

KW - Double-Blind Method

KW - Feeding Behavior/drug effects

KW - Gastric Inhibitory Polypeptide/metabolism

KW - Humans

KW - Insulin Secretion/drug effects

KW - Male

KW - Middle Aged

KW - Obesity/metabolism

KW - Peptide Fragments/pharmacology

KW - Peptides/drug effects

KW - Postprandial Period

KW - Random Allocation

KW - Receptors, Gastrointestinal Hormone/antagonists & inhibitors

KW - Subcutaneous Fat/drug effects

KW - Triglycerides/metabolism

UR - http://www.scopus.com/inward/record.url?scp=85107088281&partnerID=8YFLogxK

U2 - 10.1530/EJE-21-0135

DO - 10.1530/EJE-21-0135

M3 - Journal article

C2 - 33886495

VL - 185

SP - 33

EP - 45

JO - European Journal of Endocrinology

JF - European Journal of Endocrinology

SN - 0804-4643

IS - 1

ER -

ID: 65747238