Real-Time hypoglycemia prediction suite using continuous glucose monitoring: a safety net for the artificial pancreas

Abstract

Objective: The purpose of this study was to develop an advanced algorithm that detects pending hypoglycemia and then suspends basal insulin delivery. This approach can provide a solution to the problem of nocturnal hypoglycemia, a major concern of patients with diabetes.

Research design and methods: This real-time hypoglycemia prediction algorithm (HPA) combines five individual algorithms, all based on continuous glucose monitoring 1-min data. A predictive alarm is issued by a voting algorithm when a hypoglycemic event is predicted to occur in the next 35 min. The HPA system was developed using data derived from 21 Navigator studies that assessed Navigator function over 24 h in children with type 1 diabetes. We confirmed the function of the HPA using a separate dataset from 22 admissions of type 1 diabetic subjects. During these admissions, hypoglycemia was induced by gradual increases in the basal insulin infusion rate up to 180% from the subject's own baseline infusion rate. RESULTS Using a prediction horizon of 35 min, a glucose threshold of 80 mg/dl, and a voting threshold of three of five algorithms to predict hypoglycemia (defined as a FreeStyle plasma glucose readings <60 mg/dl), the HPA predicted 91% of the hypoglycemic events. When four of five algorithms were required to be positive, then 82% of the events were predicted.

Conclusions: The HPA will enable automated insulin-pump suspension in response to a pending event that has been detected prior to severe immediate complications.

Figure 1

Hypoglycemia alarm flowchart. The overall alarming algorithm combines multiple independent alarms into one single alarm using a voting system, where APS is the artificial Pancreas Software (24) feeding the data to the algorithms, LP is the linear prediction algorithm, SP is statistical prediction algorithm, KF is the Kalman filter algorithm, HIIR is the hybrid impulse response filter, and NLA is the numerical logical algorithm.

Figure 2

An example hypoglycemic event and successful detection using an alarm threshold of 70 mg/dl and a prediction horizon of 55 min. A high-quality digital representation of this figure is available in the online issue.

Figure 3

HPA evaluation using the UVa/Padova Metabolic Simulator following a clinical scenario in which an erroneous basal delivery, twice the usual one, was set by the user. As can be seen in the plot, without the use of HPA the subject experienced severe hypoglycemia (red dashed line) and with the algorithm this event was prevented (blue line) by suspending the basal rate for 90 min and restoring the correct basal (green dotted line). The black dashed-dotted line denotes the hypoglycemia threshold as defined by blood glucose. A high-quality digital representation of this figure is available in the online issue.