Artificial pancreas using a personalized rule-based controller achieves overnight normoglycemia in patients with type 1 diabetes

Abstract

Objective: This study assessed the efficacy of a closed-loop (CL) system consisting of a predictive rule-based algorithm (pRBA) on achieving nocturnal and postprandial normoglycemia in patients with type 1 diabetes mellitus (T1DM). The algorithm is personalized for each patient's data using two different strategies to control nocturnal and postprandial periods.

Research design and methods: We performed a randomized crossover clinical study in which 10 T1DM patients treated with continuous subcutaneous insulin infusion (CSII) spent two nonconsecutive nights in the research facility: one with their usual CSII pattern (open-loop [OL]) and one controlled by the pRBA (CL). The CL period lasted from 10 p.m. to 10 a.m., including overnight control, and control of breakfast. Venous samples for blood glucose (BG) measurement were collected every 20 min.

Results: Time spent in normoglycemia (BG, 3.9-8.0 mmol/L) during the nocturnal period (12 a.m.-8 a.m.), expressed as median (interquartile range), increased from 66.6% (8.3-75%) with OL to 95.8% (73-100%) using the CL algorithm (P<0.05). Median time in hypoglycemia (BG, <3.9 mmol/L) was reduced from 4.2% (0-21%) in the OL night to 0.0% (0.0-0.0%) in the CL night (P<0.05). Nine hypoglycemic events (<3.9 mmol/L) were recorded with OL compared with one using CL. The postprandial glycemic excursion was not lower when the CL system was used in comparison with conventional preprandial bolus: time in target (3.9-10.0 mmol/L) 58.3% (29.1-87.5%) versus 50.0% (50-100%).

Conclusions: A highly precise personalized pRBA obtains nocturnal normoglycemia, without significant hypoglycemia, in T1DM patients. There appears to be no clear benefit of CL over prandial bolus on the postprandial glycemia.

Trial registration: ClinicalTrials.gov NCT01614496.

Figures

FIG. 1.

Median and interquartile range of blood glucose (BG) values (YSI) during the overnight period. After 10 h of predictive rule-based algorithm action a convergence between all subjects in a near-normoglycemic point was observed.

FIG. 2.

Percentage of time in different blood glucose (BG) ranges corresponding to the overnight period (10 p.m.–8 a.m.): open loop (white boxes) and closed loop (striped boxes). *Difference statistically significant at P<0.05. Black circles correspond to outliers. Percentage of time in target was clearly higher with closed loop. Percentage of time with BG values <3.9 mmol/L was significantly lower with closed loop.

FIG. 3.

Blood glucose values (YSI) in the breakfast postprandial period: (A) open loop and (B) closed loop. The insulin level is shown as mean±SD values. (C) In open-loop conditions, the infusion rate is expressed in U/h. Bolus administration time was determined by each patient individually; however, for a comprehensive interpretation of data, it was represented at 8 a.m. (D) In closed-loop conditions, insulin is expressed as U. In this case, the priming bolus was administered 15 min before breakfast.