Clinical results of an automated artificial pancreas using technosphere inhaled insulin to mimic first-phase insulin secretion

Abstract

Objective: The purpose of this study was to investigate whether or not adding a fixed preprandial dose of inhaled insulin to a fully automated closed loop artificial pancreas would improve the postprandial glucose control without adding an increased risk of hypoglycemia.

Research design and methods: Nine subjects with T1DM were recruited for the study. The patients were on closed-loop control for 24 hours starting around 4:30 pm. Mixed meals (~50 g CHO) were given at 6:30 pm and 7:00 am the following day. For the treatment group each meal was preceded by the inhalation of one 10 U dose of Technosphere Insulin (TI). Subcutaneous insulin delivery was controlled by a zone model predictive control algorithm (zone-MPC). At 11:00 am, the patient exercised for 30 ± 5 minutes at 50% of predicted heart rate reserve.

Results: The use of TI resulted in increasing the median percentage time in range (70-180 mg/dl, BG) during the 5-hour postprandial period by 21.6% (81.6% and 60% in the with/without TI cases, respectively, P = .06) and reducing the median postprandial glucose peak by 33 mg/dl (172 mg/dl and 205 mg/dl in the with and without TI cases, respectively, P = .004). The median percentage time in range 80-140 mg/dl during the entire study period was 67.5% as compared to percentage time in range without the use of TI of 55.2% (P = .03).

Conclusions: Adding preprandial TI (See video supplement) to an automated closed-loop AP system resulted in superior postprandial control as demonstrated by lower postprandial glucose exposure without addition hypoglycemia.

Keywords: Health Monitoring System; artificial pancreas; closed-loop; glucose control; hypoglycemia mitigation; inhaled insulin; telemedicine; type 1 diabetes; unannounced meals; zone-MPC.

Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: HZ was a consultant to Mankind during employment at Sansum Diabetes Research Institute.

© 2015 Diabetes Technology Society.

Figures

Figure 1.

Cumulative percentage time in different ranges for all subjects in the TI case (white with cross marks) and the no TI case (gray) based on YSI BG (A) and CGM (B). The mean values for the TI case and the no TI case are represented by the blue dashed line and the red dashed line, respectively.

Figure 2.

Percentage time in different glycemic ranges based on YSI BG in the TI case (gray with diagonal line) and the no TI case (white) for the whole study (A), start of dinner to 5 hours after (B), start of breakfast to 5 hours after (C), start of exercise to 3 hours after (D), and the overnight period (12:00 am to 7:00 am) (E). *P value from the paired t test < .05 comparing the results of the TI and the no TI cases.

Figure 3.

Glucose summary results of all TI trials are summarized in (A) as mean YSI BG, 1 standard deviation (SD), and minimum and maximum YSI BG values. The control objective (80-140 mg/dl) is shown as the light yellow band and the clinically accepted region (70-180 mg/dl) as the gray band. The mean insulin delivery via CSII for all trials is shown in (B) along with 1 SD and the minimum and maximum of the insulin delivery values. The percentage of subjects received HMS alarms in a 30-minute interval is shown in (C). The time of starting the challenges and TI inhalation is shown in (D). Glucose summary results of all no TI trials are summarized in (E) as mean YSI BG, 1 SD, and minimum and maximum YSI BG values. The control objective (80-140 mg/dl) is shown as the light yellow band and the clinically accepted region (70-180 mg/dl) as the gray band. The mean insulin delivery via CSII for all trials is shown in (F) along with 1 SD and the minimum and maximum of the insulin delivery values. The percentage of subjects received HMS alarms in a 30-minute interval is shown in (G). The time of starting the challenges and TI inhalation is shown in (H).