351-OR: Six-Day Subcutaneous GIP Infusion Increases Glycemic Time-in-Range in Patients with Type 1 Diabetes

The glucagonotropic effect of glucose-dependent insulinotropic polypeptide (GIP) during insulin-induced hypoglycemia in patients with type 1 diabetes (T1D) prompted us to investigate the effect of a 6-day subcutaneous (sc) GIP infusion on glucose variability in patients with T1D. In a randomized, placebo-controlled, double-blinded, crossover study, 20 men with T1D (age [mean± SD] 26±8 years, BMI 23.8±1.8 kg/m2, HbA1c 51±10 mmol/mol), underwent 2 × 6 days of continuous sc GIP (6 pmol/kg/min) and placebo (saline) infusion, respectively, with an interposed 7-day washout period. Participants wore a continuous glucose monitoring system. GIP significantly increased daytime time in range (3.9-7.8 mmol/L) by [mean±SEM] 104±69 min/day (P=0.035) without statistically significant effects on time below range (10.1 mmol/L), mean glucose or hypoglycemic events. Compared to placebo, GIP increased hepatic fat content by 12.6±4.2 percentage points (assessed by FibroScan®) (P=0.006), decreased 24-hour systolic and diastolic blood pressure by 4.6±2.8 (P=0.001) and 2.6±1.3 mmHg (P=0.028), respectively, and increased heart rate by 4.4±2.0 beats per minute (P=0.002) (Figure). Compared to placebo, a 6-day sc GIP infusion in patients with T1D increased glycemic time in range and hepatic fat content and reduced systolic and diastolic blood pressure while increasing heart rate.