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

Diabetes Obes Metab. 2022 Jan;24(1):142-147. doi: 10.1111/dom.14545. Epub 2021 Sep 20.

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: GIP; antidiabetic drug; incretin physiology; insulin therapy; lipid-lowering therapy; type 1 diabetes.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Blood Glucose / metabolism
  • Cross-Over Studies
  • Diabetes Mellitus, Type 1* / complications
  • Diabetes Mellitus, Type 1* / drug therapy
  • Gastric Inhibitory Polypeptide / metabolism
  • Glucose / therapeutic use
  • Humans
  • Hyperglycemia* / prevention & control
  • Insulin / metabolism
  • Lipolysis
  • Male
  • Peptides / therapeutic use
  • Young Adult

Substances

  • Blood Glucose
  • Insulin
  • Peptides
  • Gastric Inhibitory Polypeptide
  • Glucose