107-OR: Six-Day Subcutaneous GIP Infusion Increases Circulating Free Fatty Acids without Altering the Adipose Tissue Transcriptome, Adipocyte GIP Receptor Levels, or Circulating Inflammation Markers in Patients with Type 1 Diabetes

Glucose-dependent insulinotropic polypeptide (GIP) has been proposed to increase adipose tissue lipolysis (at low insulin levels), adipokine secretion and circulating levels of inflammation markers via the GIP receptor (GIPR) in adipose tissue. We investigated the effect of a 6-day subcutaneous (sc) GIP infusion on circulating lipids and inflammation markers, the adipose tissue transcriptome and the presence of GIPR mRNA (ISH) in adipose tissue in patients with type 1 diabetes (T1D). In a randomized, placebo-controlled, double-blind, crossover study, 20 men with T1D (age [mean± SD] 26±8 years, BMI 23.8±1.8 kg/m2, HbA1c 51±10 mmol/mol (6.8±3.1%) underwent 2 × 6 days of continuous sc GIP (6 pmol/kg/min) infusion and placebo (saline) infusion, with an interposed 7-day washout period. Fasting blood samples were drawn frequently within the initial 3 hours and after 1 and 6 days of infusion. Adipose tissue biopsies were collected before and after 6 days of infusion. During the initial 3 hours of infusion, but not at day 1 and 6, GIP increased baseline-subtracted area under the curve of plasma free fatty acids (FFA) compared to placebo (16.8±10.4 vs. 4.4±9.2 min × mmol/L, P Disclosure S. M. Nguyen heimburger: Speaker’s Bureau; Self; AstraZeneca. T. F. Dejgaard: Advisory Panel; Self; Novo Nordisk, Consultant; Self; Boehringer Ingelheim International GmbH, Research Support; Self; AstraZeneca, Novo Nordisk, Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk. C. Pyke: Employee; Self; Novo Nordisk A/S, Stock/Shareholder; Self; Novo Nordisk A/S. M. B. Christensen: None. 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. B. Hoe: None. C. N. Nielsen: None. B. Hartmann: None. 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. F. Dela: None. A. Overgaard: Stock/Shareholder; Self; Novo Nordisk A/S. J. Storling: None. T. Vilsboll: 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. Funding The Leona M. and Harry B. Helmsley Charitable Trust (2018PG-T1D037)