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.