Outpatient Safety Assessment of an In-Home Predictive Low-Glucose Suspend System with Type 1 Diabetes Subjects at Elevated Risk of Nocturnal Hypoglycemia

Abstract

Objective: Nocturnal hypoglycemia is a common problem with type 1 diabetes. In the home setting, we conducted a pilot study to evaluate the safety of a system consisting of an insulin pump and continuous glucose monitor communicating wirelessly with a bedside computer running an algorithm that temporarily suspends insulin delivery when hypoglycemia is predicted. Research Design and Methods: After the run-in phase, a 21-night randomized trial was conducted in which each night was randomly assigned 2:1 to have either the predictive low-glucose suspend (PLGS) system active (intervention night) or inactive (control night). Three predictive algorithm versions were studied sequentially during the study for a total of 252 intervention and 123 control nights. The trial included 19 participants 18-56 years old with type 1 diabetes (hemoglobin A1c level of 6.0-7.7%) who were current users of the MiniMed Paradigm Ò REAL-Time RevelÔ System and Sof-sensor Ò glucose sensor (Medtronic Diabetes, Northridge, CA). Results: With the final algorithm, pump suspension occurred on 53% of 77 intervention nights. Mean morning glucose level was 144 -48 mg/dL on the 77 intervention nights versus 133 -57 mg/dL on the 37 control nights, with morning blood ketones >0.6 mmol/L following one intervention night. Overnight hypoglycemia was lower on intervention than control nights, with at least one value £70 mg/dL occurring on 16% versus 30% of nights, respectively, with the final algorithm. Conclusions: This study demonstrated that the PLGS system in the home setting is safe and feasible. The preliminary efficacy data appear promising with the final algorithm reducing nocturnal hypoglycemia by almost 50%.

Efficacy of an Overnight Predictive Low-Glucose Suspend System in Relation to Hypoglycemia Risk Factors in Youth and Adults With Type 1 Diabetes

“…The PLGS system used a Kalman filter to estimate the glucose level and ROC and suspended basal insulin delivery if glucose was predicted to fall below 80 mg/dl in the next 30 minutes. 4 Additional suspension/restart rules included a threshold suspend override once sensor glucose increased to 70 mg/dl, no suspension if CGM glucose concentration >230 mg/dl or if a pressure-induced sensor attenuation was suspected based on glucose ROC, 5 and restoration of basal insulin on the first CGM rise following a suspension. Audible alarms were set at 60 mg/dl.…”

“…Additional details about the system have been published. 4,5 Major eligibility criteria included having type 1 diabetes with use of daily insulin therapy for ≥1 year and use of insulin infusion pump for ≥6 months. Patients aged 4-14 and 15-45 years old required an A1C level measured with a point-of-care device of ≤8.5% and ≤8.0%, respectively, at enrollment.…”

Hypoglycemia Reduction and Accuracy of Continuous Glucose Monitoring

“…10 It was also shown that real-time CGM reduced significantly severe hypoglycemia while improving hemoglobin A1c in patients with established hypoglycemia unawareness. 11 Moreover, virtually all contemporary studies of threshold 12 or predictive 13 low glucose suspend and closedloop control (known as the artificial pancreas) [14][15][16][17][18] report significant reduction of hypoglycemia achieved by real-time control algorithms using CGM data as their principal source of information. Thus, CGM data contain valuable information that, if sufficiently accurate and correctly interpreted by the patient or by automated algorithms, can help with optimization of diabetes control and with reducing the risk for hypoglycemia.…”

Hypo- and Hyperglycemic Alarms

“…126 A larger study of the same PLGS system reduced median hypoglycemia area under the curve by 81% and extended hypoglycemia by 74% without significant increase in hyperglycemia or morning ketosis. 127 An experimental algorithm based on time series forecasting has also been evaluated by inducing hypoglycemia through exercise in a small number of patients, resulting in a reduction in occurrence of hypoglycemia. 128 Other HM approaches have incorporated insulin 129 or historical CGM 130 information and smoothly attenuate insulin delivery, rather than completely suspend/resume insulin delivery.…”