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 ± 0.856 ± 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 textless 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 textless 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.