Evaluating Glucose Control With a Novel Composite Continuous Glucose Monitoring Index.

OBJECTIVE: The objective was to describe a novel composite continuous glucose monitoring index (COGI) and to evaluate its utility, in adults with type 1 diabetes, during hybrid closed-loop (HCL) therapy and multiple daily injections (MDI) therapy combined with real-time continuous glucose monitoring (CGM). METHODS: COGI consists of three key components of glucose control as assessed by CGM: Time in range (TIR), time below range (TBR), and glucose variability (GV) (weighted by 50%, 35% and 15%). COGI ranges from 0 to 100, where 1% increase of time 7.5-10%, had significantly higher COGI during 12 weeks of HCL compared to sensor-augmented pump therapy, mean (SD), 60.3 (8.6) versus 69.5 (6.9), P 7.5% to 9.9%, use of real-time CGM led to improved COGI, 49.8 (14.2) versus 58.2 (9.1), P < .0001. In MDI users with impaired awareness of hypoglycemia, use of real-time CGM led to improved COGI, 53.4 (12.2) versus 66.7 (11.1), P < .001. CONCLUSIONS: COGI summarizes three key aspects of CGM data into a concise metric that could be utilized to evaluate the quality of glucose control and to demonstrate the incremental benefit of a wide range of treatment modalities

Variability of Insulin Requirements Over 12 Weeks of Closed-Loop Insulin Delivery in Adults With Type 1 Diabetes.

OBJECTIVE: To quantify variability of insulin requirements during closed-loop insulin delivery. RESEARCH DESIGN AND METHODS: We retrospectively analyzed overnight, daytime, and total daily insulin amounts delivered during a multicenter closed-loop trial involving 32 adults with type 1 diabetes. Participants applied hybrid day-and-night closed-loop insulin delivery under free-living home conditions over 12 weeks. The coefficient of variation was adopted to measure variability of insulin requirements in individual subjects. RESULTS: Data were analyzed from 1,918 nights, 1,883 daytime periods and 1,564 total days characterized by closed-loop use over 85% of time. Variability of overnight insulin requirements (mean [SD] coefficient of variation 31% [4]) was nearly twice as high as variability of total daily requirements (17% [3], P < 0.001) and was also higher than variability of daytime insulin requirements (22% [4], P < 0.001). CONCLUSIONS: Overnight insulin requirements were significantly more variable than daytime and total daily amounts. This may explain why some people with type 1 diabetes report frustrating variability in morning glycemia.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 and Wellcome Strategic Award (100574/Z/12/Z). Abbott Diabetes Care supplied discounted continuous glucose monitoring devices, sensors, and communication protocol to facilitate real-time connectivity. We acknowledge support by the staff at the Addenbrooke’s Wellcome Trust Clinical Research Facility. Jasdip Mangat and John Lum (Jaeb Center) supported development and validation of the closed-loop system. 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.This is the author accepted manuscript. The final version is available from the American Diabetes Association via http://dx.doi.org/10.2337/dc15-262

Assessing the effectiveness of 3 months day and night home closed-loop insulin delivery in adults with suboptimally controlled type 1 diabetes: a randomised crossover study protocol.

INTRODUCTION: Despite therapeutic advances, many people with type 1 diabetes are still unable to achieve optimal glycaemic control, limited by the occurrence of hypoglycaemia. The objective of the present study is to determine the effectiveness of day and night home closed-loop over the medium term compared with sensor-augmented pump therapy in adults with type 1 diabetes and suboptimal glycaemic control. METHODS AND ANALYSIS: The study will adopt an open label, three-centre, multinational, randomised, two-period crossover study design comparing automated closed-loop glucose control with sensor augmented insulin pump therapy. The study will aim for 30 completed participants. Eligible participants will be adults (≥18 years) with type 1 diabetes treated with insulin pump therapy and suboptimal glycaemic control (glycated haemoglobin (HbA1c)≥7.5% (58 mmol/mmol) and ≤10% (86 mmol/mmol)). Following a 4-week optimisation period, participants will undergo a 3-month use of automated closed-loop insulin delivery and sensor-augmented pump therapy, with a 4-6 week washout period in between. The order of the interventions will be random. All analysis will be conducted on an intention to treat basis. The primary outcome is the time spent in the target glucose range from 3.9 to 10.0 mmol/L based on continuous glucose monitoring levels during the 3 months free living phase. Secondary outcomes include HbA1c changes; mean glucose and time spent above and below target glucose levels. Further, participants will be invited at baseline, midpoint and study end to participate in semistructured interviews and complete questionnaires to explore usability and acceptance of the technology, impact on quality of life and fear of hypoglycaemia. ETHICS AND DISSEMINATION: Ethical approval has been obtained at all sites. Before screening, all participants will be provided with oral and written information about the trial. The study will be disseminated by peer-review publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT01961622 (ClinicalTrials.gov)

Day and night home closed-loop insulin delivery in adults with type 1 diabetes: three-center randomized crossover study.

OBJECTIVE: To evaluate the feasibility of day and night closed-loop insulin delivery in adults with type 1 diabetes under free-living conditions. RESEARCH DESIGN AND METHODS: Seventeen adults with type 1 diabetes on insulin pump therapy (means ± SD age 34 ± 9 years, HbA1c 7.6 ± 0.8%, and duration of diabetes 19 ± 9 years) participated in an open-label multinational three-center crossover study. In a random order, participants underwent two 8-day periods (first day at the clinical research facility followed by 7 days at home) of sensor-augmented insulin pump therapy (SAP) or automated closed-loop insulin delivery. The primary end point was the time when sensor glucose was in target range between 3.9 and 10.0 mmol/L during the 7-day home phase. RESULTS: During the home phase, the percentage of time when glucose was in target range was significantly higher during closed-loop compared with SAP (median 75% [interquartile range 61-79] vs. 62% [53-70], P = 0.005). Mean glucose (8.1 vs. 8.8 mmol/L, P = 0.027) and time spent above target (P = 0.013) were lower during closed loop, while time spent below target was comparable (P = 0.339). Increased time in target was observed during both daytime (P = 0.017) and nighttime (P = 0.013). CONCLUSIONS: Compared with SAP, 1 week of closed-loop insulin delivery at home reduces mean glucose and increases time in target without increasing the risk of hypoglycemia in adults with relatively well-controlled type 1 diabetes.This is the author accepted manuscript. The final version can be found published here: http://care.diabetesjournals.org/content/37/7/1931.abstract

Accuracy of Continuous Glucose Monitoring During Three Closed-Loop Home Studies Under Free-Living Conditions.

OBJECTIVES: Closed-loop (CL) systems modulate insulin delivery based on glucose levels measured by a continuous glucose monitor (CGM). Accuracy of the CGM affects CL performance and safety. We evaluated the accuracy of the Freestyle Navigator(®) II CGM (Abbott Diabetes Care, Alameda, CA) during three unsupervised, randomized, open-label, crossover home CL studies. MATERIALS AND METHODS: Paired CGM and capillary glucose values (10,597 pairs) were collected from 57 participants with type 1 diabetes (41 adults [mean±SD age, 39±12 years; mean±SD hemoglobin A1c, 7.9±0.8%] recruited at five centers and 16 adolescents [mean±SD age, 15.6±3.6 years; mean±SD hemoglobin A1c, 8.1±0.8%] recruited at two centers). Numerical accuracy was assessed by absolute relative difference (ARD) and International Organization for Standardization (ISO) 15197:2013 15/15% limits, and clinical accuracy was assessed by Clarke error grid analysis. RESULTS: Total duration of sensor use was 2,002 days (48,052 h). Overall sensor accuracy for the capillary glucose range (1.1-27.8 mmol/L) showed mean±SD and median (interquartile range) ARD of 14.2±15.5% and 10.0% (4.5%, 18.4%), respectively. Lowest mean ARD was observed in the hyperglycemic range (9.8±8.8%). Over 95% of pairs were in combined Clarke error grid Zones A and B (A, 80.1%, B, 16.2%). Overall, 70.0% of the sensor readings satisfied ISO criteria. Mean ARD was consistent (12.3%; 95% of the values fall within ±3.7%) and not different between participants (P=0.06) within the euglycemic and hyperglycemic range, when CL is actively modulating insulin delivery. CONCLUSIONS: Consistent accuracy of the CGM within the euglycemic-hyperglycemic range using the Freestyle Navigator II was observed and supports its use in home CL studies. Our results may contribute toward establishing normative CGM performance criteria for unsupervised home use of CL.Juvenile Diabetes Research Foundation (#22-2009-802), Diabetes UK (BDA07/0003549) and Seventh Framework Programme of the European Union (Grant Agreement number 247138) with additional support for the Artificial Pancreas work by National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK085621), Wellcome Strategic Award (100574/Z/12/Z), and National Institute for Health Research Cambridge Biomedical Research Centre.This is the final version of the article. It first appeared from Mary Ann Liebert via http://dx.doi.org/10.1089/dia.2015.006

Day and night closed-loop control in adults with type 1 diabetes: a comparison of two closed-loop algorithms driving continuous subcutaneous insulin infusion versus patient self-management.

OBJECTIVE: To compare two validated closed-loop (CL) algorithms versus patient self-control with CSII in terms of glycemic control. RESEARCH DESIGN AND METHODS: This study was a multicenter, randomized, three-way crossover, open-label trial in 48 patients with type 1 diabetes mellitus for at least 6 months, treated with continuous subcutaneous insulin infusion. Blood glucose was controlled for 23 h by the algorithm of the Universities of Pavia and Padova with a Safety Supervision Module developed at the Universities of Virginia and California at Santa Barbara (international artificial pancreas [iAP]), by the algorithm of University of Cambridge (CAM), or by patients themselves in open loop (OL) during three hospital admissions including meals and exercise. The main analysis was on an intention-to-treat basis. Main outcome measures included time spent in target (glucose levels between 3.9 and 8.0 mmol/L or between 3.9 and 10.0 mmol/L after meals). RESULTS: Time spent in the target range was similar in CL and OL: 62.6% for OL, 59.2% for iAP, and 58.3% for CAM. While mean glucose level was significantly lower in OL (7.19, 8.15, and 8.26 mmol/L, respectively) (overall P = 0.001), percentage of time spent in hypoglycemia (<3.9 mmol/L) was almost threefold reduced during CL (6.4%, 2.1%, and 2.0%) (overall P = 0.001) with less time ≤2.8 mmol/L (overall P = 0.038). There were no significant differences in outcomes between algorithms. CONCLUSIONS: Both CAM and iAP algorithms provide safe glycemic control