Adding heart rate signal to a control-to-range artificial pancreas system improves the protection against hypoglycemia during exercise in type 1 diabetes

Abstract

Background: We present a clinical trial establishing the feasibility of a control-to-range (CTR) closed-loop system informed by heart rate (HR) and assess the effect of HR information added to CTR on the risk for hypoglycemia during and after exercise.

Subjects and methods: Twelve subjects with type 1 diabetes (five men, seven women; weight, 68.9 ± 3.1 kg; age, 38 ± 3.3 years; glycated hemoglobin, 6.9 ± 0.2%) participated in a randomized crossover clinical trial comparing CTR versus CTR+HR in two 26-h admissions, each including 30 min of mild exercise. The CTR algorithm was implemented in the DiAs portable artificial pancreas platform based on an Android(®) (Google, Mountainview, CA) smartphone. We assessed blood glucose (BG) decline during exercise, the Low BG Index (LBGI) (a measure of hypoglycemic risk), number of hypoglycemic episodes (BG <70 mg/dL) and overall glucose control (percentage time within the target range 70 mg/dL ≤ BG ≤ 180 mg/dL).

Results: Using HR to inform the CTR algorithm reduced significantly the BG decline during exercise (P=0.022), indicated marginally lower LBGI (P=0.3) and fewer hypoglycemic events during exercise (none vs. two events; P=0.16), and resulted in overall higher percentage time within the target range (81% vs. 75%; P=0.2). LBGI and average BG remained unchanged overall, during recovery, and overnight.

Conclusions: HR-informed closed-loop control can be implemented in a portable artificial pancreas. Although closed loop has been shown to reduce hypoglycemia, adding HR signal may further limit the risk for hypoglycemia during and immediately after exercise. The most prominent effect of adding HR information is reduced BG decline during exercise, without deterioration of overall glycemic control.

Figures

FIG. 1.

Study and protocol design. (A) Subjects were admitted twice at the University of Virginia clinical research center for 24 h to test one of the artificial pancreas systems (heart rate–enhanced or standard) in a randomized order. (B) Both admissions followed the same timeline. Bkfst, breakfast; CGM, continuous glucose monitor.

FIG. 2.

Heart rate increased consistently during the mild exercise bout and returned to basal values within 15 min afterward. In all bouts, 125% of the basal value was reached within 8 min of onset on average (maximum, 22 min).

FIG. 3.

On average, the plasma glucose level did not decline during exercise and only moderately afterward when using control-to-range plus heart rate (squares with black line). In contrast, under standard control-to-range the average plasma glucose decline was pronounced throughout the exercise bout and moderately amplified thereafter (diamonds with gray line). Maximum separation was achieved at min 60 after onset of exercise (−3.4 mg/dL vs. −27.7 mg/dL). BG, blood glucose.

FIG. 4.

(A) The risk of hypoglycemia as measured by the Low Blood Glucose Index (mean and SE values reported) was similar overall in both admissions but seems reduced during and in the hours after exercise. (B) This possible reduction did not come at the cost of lesser glycemic control as the time spent in hypoglycemia. In all phases of the admission average percentage in euglycemia seems slightly better using the heart rate (HR)–enhanced system.