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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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. / Heimburger, Sebastian M.; Nielsen, Chris N.; Calanna, Salvatore; Holst, Jens J.; Vilsbøll, Tina; Knop, Filip K.; Christensen, Mikkel B.
In: Diabetes, Obesity and Metabolism, Vol. 24, No. 1, 2022, p. 142-147.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - 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
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.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
U2 - 10.1111/dom.14545
DO - 10.1111/dom.14545
M3 - Journal article
C2 - 34490741
VL - 24
SP - 142
EP - 147
JO - Diabetes, Obesity and Metabolism
JF - Diabetes, Obesity and Metabolism
SN - 1462-8902
IS - 1
ER -
ID: 279651009