Overnight Closed-Loop Insulin Delivery in Young People With Type 1 Diabetes: A Free-Living, Randomized Clinical Trial

Abstract

OBJECTIVETo evaluate feasibility, safety, and efficacy of overnight closed-loop insulin delivery in free-living youth with type 1 diabetes.RESEARCH DESIGN AND METHODSOvernight closed loop was evaluated at home by 16 pump-treated adolescents with type 1 diabetes aged 12–18 years. Over a 3-week period, overnight insulin delivery was directed by a closed-loop system, and on another 3-week period sensor-augmented therapy was applied. The order of interventions was random. The primary end point was time when adjusted sensor glucose was between 3.9 and 8.0 mmol/L from 2300 to 0700 h.RESULTSClosed loop was constantly applied over at least 4 h on 269 nights (80%); sensor data were collected over at least 4 h on 282 control nights (84%). Closed loop increased time spent with glucose in target by a median 15% (interquartile range −9 to 43; P < 0.001). Mean overnight glucose was reduced by a mean 14 (SD 58) mg/dL (P < 0.001). Time when glucose was <70 mg/dL was low in both groups, but nights with glucose <63 mg/dL for at least 20 min were less frequent during closed loop (10 vs. 17%; P = 0.01). Despite lower total daily insulin doses by a median 2.3 (interquartile range −4.7 to 9.3) units (P = 0.009), overall 24-h glucose was reduced by a mean 9 (SD 41) mg/dL (P = 0.006) during closed loop.CONCLUSIONSUnsupervised home use of overnight closed loop in adolescents with type 1 diabetes is safe and feasible. Glucose control was improved during the day and night with fewer episodes of nocturnal hypoglycemia.

Multinight “Bedside” Closed-Loop Control for Patients with Type 1 Diabetes

“…[12][13][14] This new study confirms the previous findings and adds two unique features: (1) a portable platform using a consumer electronics device (smartphone) to run the CLC system and all CGM, pump, and remote communications and (2) a control algorithm specifically designed to ''slide'' the patients' glucose levels to a target of 120 mg/dL at wakeup, thereby resetting their metabolic state overnight to near-normoglycemic morning BG levels, on consecutive nights. As a result, this study demonstrated not only significant improvement in overnight glucose control on CLC, but also significant improvement of patients' control on the next day.…”

“…9 The transition of CLC to a wearable outpatient system began in 2012 with the introduction of the Diabetes Assistant (DiAs)-the first wearable CLC system using a smartphone as a computational platform for its control algorithm. 10,11 Other recent trials confirmed the effectiveness of overnight CLC at diabetes camps for children 12 and at patients' homes, 13,14 placing laptop computers equipped with control algorithms at their patients' bedside.…”

Insulin delivery and nocturnal glucose control in children and adolescents with type 1 diabetes

“…Depending on control algorithm and the population, mean overnight glucose is lower [29,31,34,36,38], similar [27,32,35,37] or slightly elevated [28,33] than during control therapy.…”

“…Unsupervised free-living overnight use of a MPC algorithm driven closed-loop in adolescents over a period of 3 weeks showed significant improvements in time spent within target range by a median 15 percentage points, reduced mean glucose by a mean 0.8 mmol/l, and reduced the number of nights with glucose readings below 3.5 mmol/l compared to sensor augmented pump therapy [38]. A slightly revised version of this closed-loop system was tested in the longest randomized home study in children and adolescents to date.…”

Mixed Meal Model in Type 1 Diabetes

“…In recent years, BG control systems that maintain normoglycemia automatically by closed-loop continuous infusion of insulin have taken particularly large strides towards its commercial development. Some studies [3] already have had successful results for overnight freeliving conditions, whereas more recently there is focus on postprandial BG control [4] and its compliance with clinical guidelines considers patient input of the carbohydrate content of the meal. Nonetheless, BG control performance has been shown to be under-mined by consumption of high-fat mixed meal [5], thus revealing that not only glucose but also fatty acid metabolism is indispensable in the mathematical representation of postprandial glucose-insulin metabolism in T1DM.…”