Forskning
Udskriv Udskriv
Switch language
Hvidovre Hospital - en del af Københavns Universitetshospital
E-pub ahead of print

Glucose-dependent insulinotropic polypeptide induces lipolysis during stable basal insulin substitution and hyperglycaemia in men with type 1 diabetes: a randomized, double-blind, placebo-controlled, crossover clinical trial

Publikation: Bidrag til tidsskriftTidsskriftartikelpeer review

Harvard

APA

CBE

MLA

Vancouver

Author

Bibtex

@article{bc58cff0212747d4a45203b3a4367a50,
title = "Glucose-dependent insulinotropic polypeptide induces lipolysis during stable basal insulin substitution and hyperglycaemia in men with type 1 diabetes: a randomized, double-blind, placebo-controlled, crossover clinical trial",
abstract = "Glucose-dependent insulinotropic polypeptide (GIP) plays an important role in the glucose and lipid metabolism. We investigated the effects of exogenous GIP on lipid metabolism during time of stable insulin levels. Ten male patients with type 1 diabetes without endogenous insulin secretion (C-peptide-negative, mean [±SD] age 26 ± 4years, body mass index 24 [±2] kg/m2 , glycated haemoglobin 56 [±8] mmol/mol or 7.3 [±0.8]%) were studied in a randomized, double-blind, placebo-controlled, crossover study with continuous intravenous infusions of GIP (4 pmol/kg/min) or placebo (saline), during two separate 90-minute hyperglycaemic (12 mmol/L) clamps with basal insulin substitution (0.1-0.2 mU/kg/min). Plasma glycerol concentrations increased from baseline during GIP infusion and decreased during placebo infusion (baseline-subtracted area under the curve [bsAUC] 703 ± 407 vs. -262 ± 240 μmol/L × min, respectively; P < 0.001). Free fatty acids (FFAs) increased during GIP infusions (bsAUC 5505 ± 2170 μEq/L × min) and remained unchanged during placebo infusion (bsAUC -74 ± 2363 μEq/L × min), resulting in a significant difference between GIP and placebo infusions (P < 0.001). Plasma concentrations of glucose, insulin, glucagon-like peptide-1 and glucagon were similar during GIP and placebo infusions. GIP increased plasma glycerol and FFAs in patients with type 1 diabetes during hyperglycaemia and stable basal insulin levels. This supports a direct lipolytic effect of GIP at high glucose and low levels of plasma insulin.",
keywords = "antidiabetic drug, GIP, incretin physiology, insulin therapy, lipid-lowering therapy, type 1 diabetes",
author = "Heimburger, {Sebastian M} and Nielsen, {Chris N} and Salvatore Calanna and Holst, {Jens J} and Tina Vilsb{\o}ll and Knop, {Filip K} and Christensen, {Mikkel B}",
note = "This article is protected by copyright. All rights reserved.",
year = "2021",
month = sep,
day = "6",
doi = "10.1111/dom.14545",
language = "English",
journal = "Diabetes, Obesity and Metabolism",
issn = "1462-8902",
publisher = "Wiley-Blackwell Publishing Ltd",

}

RIS

TY - JOUR

T1 - Glucose-dependent insulinotropic polypeptide induces lipolysis during stable basal insulin substitution and hyperglycaemia in men with type 1 diabetes

T2 - a randomized, double-blind, placebo-controlled, crossover clinical trial

AU - Heimburger, Sebastian M

AU - Nielsen, Chris N

AU - Calanna, Salvatore

AU - Holst, Jens J

AU - Vilsbøll, Tina

AU - Knop, Filip K

AU - Christensen, Mikkel B

N1 - This article is protected by copyright. All rights reserved.

PY - 2021/9/6

Y1 - 2021/9/6

N2 - Glucose-dependent insulinotropic polypeptide (GIP) plays an important role in the glucose and lipid metabolism. We investigated the effects of exogenous GIP on lipid metabolism during time of stable insulin levels. Ten male patients with type 1 diabetes without endogenous insulin secretion (C-peptide-negative, mean [±SD] age 26 ± 4years, body mass index 24 [±2] kg/m2 , glycated haemoglobin 56 [±8] mmol/mol or 7.3 [±0.8]%) were studied in a randomized, double-blind, placebo-controlled, crossover study with continuous intravenous infusions of GIP (4 pmol/kg/min) or placebo (saline), during two separate 90-minute hyperglycaemic (12 mmol/L) clamps with basal insulin substitution (0.1-0.2 mU/kg/min). Plasma glycerol concentrations increased from baseline during GIP infusion and decreased during placebo infusion (baseline-subtracted area under the curve [bsAUC] 703 ± 407 vs. -262 ± 240 μmol/L × min, respectively; P < 0.001). Free fatty acids (FFAs) increased during GIP infusions (bsAUC 5505 ± 2170 μEq/L × min) and remained unchanged during placebo infusion (bsAUC -74 ± 2363 μEq/L × min), resulting in a significant difference between GIP and placebo infusions (P < 0.001). Plasma concentrations of glucose, insulin, glucagon-like peptide-1 and glucagon were similar during GIP and placebo infusions. GIP increased plasma glycerol and FFAs in patients with type 1 diabetes during hyperglycaemia and stable basal insulin levels. This supports a direct lipolytic effect of GIP at high glucose and low levels of plasma insulin.

AB - Glucose-dependent insulinotropic polypeptide (GIP) plays an important role in the glucose and lipid metabolism. We investigated the effects of exogenous GIP on lipid metabolism during time of stable insulin levels. Ten male patients with type 1 diabetes without endogenous insulin secretion (C-peptide-negative, mean [±SD] age 26 ± 4years, body mass index 24 [±2] kg/m2 , glycated haemoglobin 56 [±8] mmol/mol or 7.3 [±0.8]%) were studied in a randomized, double-blind, placebo-controlled, crossover study with continuous intravenous infusions of GIP (4 pmol/kg/min) or placebo (saline), during two separate 90-minute hyperglycaemic (12 mmol/L) clamps with basal insulin substitution (0.1-0.2 mU/kg/min). Plasma glycerol concentrations increased from baseline during GIP infusion and decreased during placebo infusion (baseline-subtracted area under the curve [bsAUC] 703 ± 407 vs. -262 ± 240 μmol/L × min, respectively; P < 0.001). Free fatty acids (FFAs) increased during GIP infusions (bsAUC 5505 ± 2170 μEq/L × min) and remained unchanged during placebo infusion (bsAUC -74 ± 2363 μEq/L × min), resulting in a significant difference between GIP and placebo infusions (P < 0.001). Plasma concentrations of glucose, insulin, glucagon-like peptide-1 and glucagon were similar during GIP and placebo infusions. GIP increased plasma glycerol and FFAs in patients with type 1 diabetes during hyperglycaemia and stable basal insulin levels. This supports a direct lipolytic effect of GIP at high glucose and low levels of plasma insulin.

KW - antidiabetic drug

KW - GIP

KW - incretin physiology

KW - insulin therapy

KW - lipid-lowering therapy

KW - type 1 diabetes

UR - http://www.scopus.com/inward/record.url?scp=85115111981&partnerID=8YFLogxK

U2 - 10.1111/dom.14545

DO - 10.1111/dom.14545

M3 - Journal article

C2 - 34490741

JO - Diabetes, Obesity and Metabolism

JF - Diabetes, Obesity and Metabolism

SN - 1462-8902

ER -

ID: 67568207