ABSTRACT
OBJECTIVE: The rapid insulin-alone artificial pancreas improves glycemia in type 1 diabetes but daytime control remains suboptimal. We propose two novel dual-hormone artificial pancreas systems. RESEARCH DESIGN AND METHODS: We conducted a randomized crossover trial comparing a rapid insulin-alone artificial pancreas with rapid insulin-and-pramlintide and with regular insulin-and-pramlintide artificial pancreas systems in adults with type 1 diabetes. Participants were assigned to the interventions in random order during three 24-h inpatient visits. Each visit was preceded by an outpatient hormonal open-loop run-in period of 10-14 days. The dual-hormone artificial pancreas delivered pramlintide in a basal-bolus manner, using a novel dosing algorithm, with a fixed ratio relative to insulin. The primary outcome was time in the range 3.9-10.0 mmol/L. RESULTS: Compared with the rapid insulin-alone artificial pancreas system, the rapid insulin-and-pramlintide system increased the time in range from 74% (SD 18%) to 84% (13%) (P = 0.0014), whereas the regular insulin-and-pramlintide system did not change the time in range (69% [19%]; P = 0.22). The increased time in range with the rapid insulin-and-pramlintide system was due to improved daytime control (daytime time in range increased from 63% [23%] to 78% [16%], P = 0.0004). There were 11 (1 per 2.5 days) hypoglycemic events (<3.3 mmol/L with symptoms or <3.0 mmol/L irrespective of symptoms) with the rapid insulin-alone system, compared with 12 (1 per 2.3 days) and 18 (1 per 1.4 days) with the rapid and regular insulin-and-pramlintide systems, respectively. Gastrointestinal symptoms were reported after 0% (0 of 112) of meals with the rapid insulin-alone system, compared with 6% (6 of 108) and 11% (11 of 104) with the rapid and regular insulin-and-pramlintide systems, respectively; none of the symptoms were severe. CONCLUSIONS: A novel rapid insulin-and-pramlintide artificial pancreas improves glucose control compared with a rapid insulin-alone artificial pancreas (ClinicalTrials.gov number NCT02814123).
Subject(s)
Diabetes Mellitus, Type 1/drug therapy , Insulin Infusion Systems , Insulin/administration & dosage , Islet Amyloid Polypeptide/administration & dosage , Pancreas, Artificial , Adolescent , Adult , Algorithms , Blood Glucose/drug effects , Blood Glucose/metabolism , Child , Cross-Over Studies , Diabetes Mellitus, Type 1/blood , Drug Therapy, Combination , Female , Humans , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/adverse effects , Insulin/adverse effects , Insulin Infusion Systems/adverse effects , Insulin, Regular, Human/administration & dosage , Insulin, Regular, Human/adverse effects , Islet Amyloid Polypeptide/adverse effects , Male , Meals , Pancreas, Artificial/adverse effects , Young AdultABSTRACT
Background: FreeStyle Libre is a factory-calibrated continuous 14-day glucose sensor. Little is known about the accuracy of FreeStyle Libre as a function of sensor age. Methods: We assessed the accuracy of FreeStyle Libre in 14 adults with type 1 diabetes. Each study participant attended our research facility for two or three 24-h visits, during which they wore a FreeStyle Libre aged 0-1 day, 5-7 days, or 13-14 days. Plasma glucose levels were measured every 10-30 min using YSI2300 STAT Plus Analyser. Participants also wore Dexcom G5® glucose sensor aged 1-2 days. We assessed sensors' accuracy using mean absolute relative difference (MARD) between FreeStyle Libre, the Dexcom G5 sensor, and plasma glucose. Results: We had 1930 pairs of FreeStyle Libre sensor-plasma glucose measurements, collected from 36 FreeStyle Libre sensors, 18 of which were sensors aged 0-1 day, 9 were sensors aged 5-7 days, and 9 were sensors aged 13-14 days. The mean and median MARD for FreeStyle Libre sensors aged 0-1 days were 14.5% and 11.2%, respectively, and for sensors aged 13-14 days were 14.7% and 11.2%, respectively, but for sensors aged 5-7 days were 7.8% and 6.6%, respectively (P = 0.03 vs. sensors aged 0-1 days, and P = 0.06 vs. sensors aged 13-14 days). The percentage of points falling in the potentially dangerous zones C, D, or E in Clarke's error grid analysis were 1.9% for FreeStyle Libre sensors aged 0-1 day, 0.2% for sensors aged 5-7 days, and 0.4% for sensors aged 13-14 days. The overall accuracy of FreeStyle Libre and Dexcom G5 sensor was the same (mean MARD 12.8% and 12.5%, respectively; P = 0.57). Conclusions: FreeStyle Libre's accuracy is adequate during its entire lifetime but is least accurate during its first and last days. ClinicalTrials.gov Identifier: NCT02814123.