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E-pub ahead of print

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

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INTRODUCTION: Glucose-dependent insulinotropic polypeptide (GIP) contributes importantly to glucose and lipid metabolism. We investigated the effects of exogenous GIP on lipid metabolism during stable insulin levels.

METHODS: Ten male patients with type 1 diabetes without endogenous insulin secretion (C-peptide negative) (age [mean ± SD: 26 ± 4 years; BMI: 24 ± 2 kg/m2 ; HbA1c 7.3 ± 0.8% [56 ± 8 mmol/mol]) 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 hyperglycemic (12 mmol/L) clamps with basal insulin substitution (0.1-0.2 mU/kg/min).

RESULTS: 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 (FFA) 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, GLP-1 and glucagon were similar during GIP and placebo infusions.

CONCLUSIONS: GIP increased plasma glycerol and FFA in patients with type 1 diabetes during hyperglycemia and stable basal insulin levels. This supports a direct lipolytic effect of GIP at high glucose and low levels of plasma insulin.

TRIAL REGISTRATION: ClinicalTrials.gov NCT03195257 None. This article is protected by copyright. All rights reserved.

OriginalsprogEngelsk
TidsskriftDiabetes, Obesity and Metabolism
ISSN1462-8902
DOI
StatusE-pub ahead of print - 6 sep. 2021

ID: 67568207