Bolusing frequency and amount impacts glucose control during hybrid closed-loop.

AIM: To compare bolus insulin delivery patterns during closed-loop home studies in adults with suboptimally [HbA1c 58-86 mmol/mol (7.5%-10%)] and well-controlled [58 mmol/mol (< 7.5%)] Type 1 diabetes. METHODS: Retrospective analysis of daytime and night-time insulin delivery during home use of closed-loop over 4 weeks. Daytime and night-time controller effort, defined as amount of insulin delivered by closed-loop relative to usual basal insulin delivery, and daytime bolus effort, defined as total bolus insulin delivery relative to total daytime insulin delivery were compared between both cohorts. Correlation analysis was performed between individual bolus behaviour (bolus effort and frequency) and daytime controller efforts, and proportion of time spent within and below sensor glucose target range. RESULTS: Individuals with suboptimally controlled Type 1 diabetes had significantly lower bolus effort (P = 0.038) and daily bolus frequency (P < 0.001) compared with those with well-controlled diabetes. Controller effort during both daytime (P = 0.007) and night-time (P = 0.005) were significantly higher for those with suboptimally controlled Type 1 diabetes. Time when glucose was within the target range (3.9-10.0 mmol/L) during daytime correlated positively with bolus effort (r = 0.37, P = 0.016) and bolus frequency (r = 0.33, P = 0.037). Time when glucose was below the target range during daytime was comparable in both groups (P = 0.36), and did not correlate significantly with bolus effort (r = 0.28, P = 0.066) or bolus frequency (r = -0.21, P = 0.19). CONCLUSION: More frequent bolusing and higher proportion of insulin delivered as bolus during hybrid closed-loop use correlated positively with time glucose was in target range. This emphasises the need for user input and educational support to benefit from this novel therapeutic modality.Seventh Framework Programme of the European Union (ICT FP7- 247138). Additional support for the Artificial Pancreas work by JDRF, National Institute for Health Research Cambridge Biomedical Research Centre, Wellcome Strategic Award (100574/Z/12/Z), EC Horizon 2020 (H2020-SC1-731560), NIDDK (DP3DK112176 and 1UC4DK108520-01), Efficacy and Mechanism Evaluation Programme of National Institute for Health Research (14/23/09) and Helmsley Trust (2016PG-T1D045 and #2016PG-T1D046)

Behavioral Patterns and Associations with Glucose Control During 12-Week Randomized Free-Living Clinical Trial of Day and Night Hybrid Closed-Loop Insulin Delivery in Adults with Type 1 Diabetes

$\textbf{Objectives}$: We evaluated patterns of meal intake, insulin bolus delivery, and fingerstick glucose measurements during hybrid closed-loop and sensor-augmented pump (SAP) therapy, including associations with glucose control. $\textbf{Methods}$: Data were retrospectively analyzed from pump-treated adults with type 1 diabetes who underwent, in random order, 12 weeks free-living closed-loop (n = 32) and 12 weeks SAP (n = 33) periods. We quantified daily patterns of main meals, snacks, prandial insulin boluses, correction boluses, and fingerstick glucose measurements by analyzing data recorded on the study glucometer and on study insulin pump. $\textbf{Results}$: We analyzed 1942 closed-loop days and 2530 SAP days. The total number of insulin boluses was reduced during closed-loop versus SAP periods by mean 1.0 per day (95% confidence interval 0.6–1.4, P < 0.001) mainly because of a reduced number of correction boluses by mean 0.7 per day (0.4–1.0, P < 0.001). Other behavioral patterns were unchanged. The carbohydrate content of snacks but not the number of snacks was positively correlated with (1) glycemic variability as measured by standard deviation of sensor glucose (closed-loop P < 0.05; SAP P < 0.01), (2) mean sensor glucose (P < 0.05), and (3) postintervention HbA1c (P < 0.05). Behavioral patterns explained 47% of between-subject variance in glucose variability during SAP period and 30%–33% of variance of means sensor glucose and postintervention HbA1c. $\textbf{Conclusion}$: Fewer correction boluses are delivered during closed-loop period. The size of snacks appears to worsen glucose control possibly because of carbohydrate-rich content of snacks. Modifiable behavioral patterns may be important determinants of glucose control.We acknowledge support by the staff at the Addenbrooke's Wellcome Trust Clinical Research Facility. Josephine Hayes (University of Cambridge) provided administrative support. Karen Whitehead (University of Cambridge) provided laboratory support. We acknowledge support by the staff at Profil Institut, Krisztina Schmitz-Grozs provided support as a research physician, Martina Haase supported the study as an insulin pump expert, and Maren Luebkert, Kirstin Kuschma, and Elke Przetak provided administrative, coordinating, and documentation support. Barbara Semlitsch and Markus Schauer (both from Medical University of Graz) supported the study as insulin pump experts. Funding was by Seventh Framework Programme of the European Union (ICT FP7-247138). Additional support for the Artificial Pancreas work was by JDRF, National Institute for Health Research Cambridge Biomedical Research Centre, Wellcome Strategic Award (100574/Z/12/Z), EC Horizon 2020 (H2020-SC1-731560), NIDDK (DP3DK112176 and 1UC4DK108520-01), Efficacy and Mechanism Evaluation Programme of National Institute for Health Research (14/23/09), and Helmsley Trust (Nos. 2016PG-T1D045 and 2016PG-T1D046). Abbott Diabetes Care supplied discounted continuous glucose monitoring devices, sensors, and communication protocol to facilitate real-time connectivity

Home Use of an Artificial Beta Cell in Type 1 Diabetes.

BACKGROUND: The feasibility, safety, and efficacy of prolonged use of an artificial beta cell (closed-loop insulin-delivery system) in the home setting have not been established. METHODS: In two multicenter, crossover, randomized, controlled studies conducted under free-living home conditions, we compared closed-loop insulin delivery with sensor-augmented pump therapy in 58 patients with type 1 diabetes. The closed-loop system was used day and night by 33 adults and overnight by 25 children and adolescents. Participants used the closed-loop system for a 12-week period and sensor-augmented pump therapy (control) for a similar period. The primary end point was the proportion of time that the glucose level was between 70 mg and 180 mg per deciliter for adults and between 70 mg and 145 mg per deciliter for children and adolescents. RESULTS: Among adults, the proportion of time that the glucose level was in the target range was 11.0 percentage points (95% confidence interval [CI], 8.1 to 13.8) greater with the use of the closed-loop system day and night than with control therapy (P<0.001). The mean glucose level was lower during the closed-loop phase than during the control phase (difference, -11 mg per deciliter; 95% CI, -17 to -6; P<0.001), as were the area under the curve for the period when the glucose level was less than 63 mg per deciliter (39% lower; 95% CI, 24 to 51; P<0.001) and the mean glycated hemoglobin level (difference, -0.3%; 95% CI, -0.5 to -0.1; P=0.002). Among children and adolescents, the proportion of time with the nighttime glucose level in the target range was higher during the closed-loop phase than during the control phase (by 24.7 percentage points; 95% CI, 20.6 to 28.7; P<0.001), and the mean nighttime glucose level was lower (difference, -29 mg per deciliter; 95% CI, -39 to -20; P<0.001). The area under the curve for the period in which the day-and-night glucose levels were less than 63 mg per deciliter was lower by 42% (95% CI, 4 to 65; P=0.03). Three severe hypoglycemic episodes occurred during the closed-loop phase when the closed-loop system was not in use. CONCLUSIONS: Among patients with type 1 diabetes, 12-week use of a closed-loop system, as compared with sensor-augmented pump therapy, improved glucose control, reduced hypoglycemia, and, in adults, resulted in a lower glycated hemoglobin level. (Funded by the JDRF and others; AP@home04 and APCam08 ClinicalTrials.gov numbers, NCT01961622 and NCT01778348.).JDRF (22-2011-668) and Seventh Framework Programme of the European Union (ICT FP7- 247138). Additional support for the Artificial Pancreas work by National Institute for Health Research Cambridge Biomedical Research Centre and Wellcome Strategic Award (100574/Z/12/Z). Abbott Diabetes Care supplied discounted continuous glucose monitoring devices, sensors, and details of communication protocol to facilitate real-time connectivity. Diasend provided discounted platform for data upload.This is the final version of the article. It was first available from Massachusetts Medical Society via http://dx.doi.org/10.1056/NEJMoa150935

Closing the Loop

Background Two widely used artificial pancreas (AP) control algorithms are the model predictive control (MPC) and the proportional integral derivative (PID) algorithms. Numerous studies across different settings have used both algorithms with positive results, but there has never been a randomized clinical trial directly comparing the effectiveness of each. This study aimed to compare individual-personalized MPC and PID controls under nonideal but comparable clinical conditions. Methods After a pilot safety and feasibility study (n= 10), closed-loop control (CLC) was conducted and evaluated in a randomized, crossover trial that included 20 additional adults with type 1 diabetes. Both the MPC and PID algorithms were compared during supervised 27.5 hour CLC sessions. The algorithms were tested by evaluating control performance following a 65 g dinner, 50 g breakfast, and unannounced..