648-P: Glucose-Dependent Insulinotropic Polypeptide (GIP) Induces Lipolysis during Stable Basal Insulin Substitution and Hyperglycemia in Men with Type 1 Diabetes

Abstract

Glucose-dependent insulinotropic polypeptide (GIP) contributes importantly to postprandial insulin secretion, and - perhaps primarily due to this insulinotropic effect - affects glucose and lipid metabolism. We investigated the effects of exogenous GIP on lipid metabolism during hyperglycemia and stable insulin levels. Ten male patients with type 1 diabetes without endogenous insulin secretion (C-peptide negative), aged [mean±SD: 26±4 years; BMI: 24±2 kg/m2; HbA1c 7.3±0.8%) were studied in a randomized, double-blind, 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). Plasma glycerol concentrations increased from baseline during GIP infusions and decreased during placebo infusions (baseline-subtracted area under the curve (bsAUC): 703±407 vs. -262±240 µmol/L × min, respectively, P<0.001). Free fatty acids increased only during GIP infusions (bsAUC: 5,431±6,393 during GIP vs. -74±2,363 µmol/l × min during placebo infusion, P<0.05). Plasma concentrations of glucose, insulin, and glucagon were similar during GIP and placebo infusions (P=NS). Compared to placebo, GIP increased plasma glycerol and free fatty acids in patients with type 1 diabetes during hyperglycemia and stable basal insulin levels. With this experimental design it was possible to clearly identify an important effect of GIP on lipolysis in humans. Disclosure C. N. Nielsen: None. S. M. Nguyen heimbürger: Speaker’s Bureau; Self; AstraZeneca. S. Calanna: Employee; Self; Novo Nordisk A/S. J. J. Holst: Consultant; Self; Novo Nordisk, Other Relationship; Self; Antag Therapeutics, Bainan Biotech, MSD Corporation, Novo Nordisk, Other Relationship; Spouse/Partner; Antag Therapeutics, Bainan Biotech, Synklino ApS. T. Vilsbøll: Consultant; Self; Amgen Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, Gilead Sciences, Inc., Lilly Diabetes, Merck Sharp & Dohme Corp., Mundipharma International, Novo Nordisk, Sanofi, Sun Pharmaceutical Industries Ltd. F. K. Knop: Advisory Panel; Self; MSD Corporation, Novo Nordisk A/S, Sanofi, Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Novo Nordisk A/S, Pharmacosmos, Zealand Pharma A/S, Research Support; Self; Novo Nordisk A/S, Zealand Pharma A/S, Speaker’s Bureau; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, MSD Corporation, Novo Nordisk A/S. M. B. Christensen: None.