OBJECTIVETo minimize hypoglycemia in subjects with type 1 diabetes by automated glucagon delivery in a closed-loop insulin delivery system.RESEARCH DESIGN AND METHODSAdult subjects with type 1 diabetes underwent one closed-loop study with insulin plus placebo and one study with insulin plus glucagon, given at times of impending hypoglycemia. Seven subjects received glucagon using high-gain parameters, and six subjects received glucagon in a more prolonged manner using low-gain parameters. Blood glucose levels were measured every 10 min and insulin and glucagon infusions were adjusted every 5 min. All subjects received a portion of their usual premeal insulin after meal announcement.RESULTSAutomated glucagon plus insulin delivery, compared with placebo plus insulin, significantly reduced time spent in the hypoglycemic range (15 ± 6 vs. 40 ± 10 min/day, P = 0.04). Compared with placebo, high-gain glucagon delivery reduced the frequency of hypoglycemic events (1.0 ± 0.6 vs. 2.1 ± 0.6 events/day, P = 0.01) and the need for carbohydrate treatment (1.4 ± 0.8 vs. 4.0 ± 1.4 treatments/day, P = 0.01). Glucagon given with low-gain parameters did not significantly reduce hypoglycemic event frequency (P = NS) but did reduce frequency of carbohydrate treatment (P = 0.05).CONCLUSIONSDuring closed-loop treatment in subjects with type 1 diabetes, high-gain pulses of glucagon decreased the frequency of hypoglycemia. Larger and longer-term studies will be required to assess the effect of ongoing glucagon treatment on overall glycemic control.

BackgroundWrist-worn activity monitors are often used to monitor heart rate (HR) and energy expenditure (EE) in a variety of settings including more recently in medical applications. The use of real-time physiological signals to inform medical systems including drug delivery systems and decision support systems will depend on the accuracy of the signals being measured, including accuracy of HR and EE. Prior studies assessed accuracy of wearables only during steady-state aerobic exercise.ObjectiveThe objective of this study was to validate the accuracy of both HR and EE for 2 common wrist-worn devices during a variety of dynamic activities that represent various physical activities associated with daily living including structured exercise.MethodsWe assessed the accuracy of both HR and EE for two common wrist-worn devices (Fitbit Charge 2 and Garmin vívosmart HR+) during dynamic activities. Over a 2-day period, 20 healthy adults (age: mean 27.5 [SD 6.0] years; body mass index: mean 22.5 [SD 2.3] kg/m2; 11 females) performed a maximal oxygen uptake test, free-weight resistance circuit, interval training session, and activities of daily living. Validity was assessed using an HR chest strap (Polar) and portable indirect calorimetry (Cosmed). Accuracy of the commercial wearables versus research-grade standards was determined using Bland-Altman analysis, correlational analysis, and error bias.ResultsFitbit and Garmin were reasonably accurate at measuring HR but with an overall negative bias. There was more error observed during high-intensity activities when there was a lack of repetitive wrist motion and when the exercise mode indicator was not used. The Garmin estimated HR with a mean relative error (RE, %) of −3.3% (SD 16.7), whereas Fitbit estimated HR with an RE of −4.7% (SD 19.6) across all activities. The highest error was observed during high-intensity intervals on bike (Fitbit: −11.4% [SD 35.7]; Garmin: −14.3% [SD 20.5]) and lowest error during high-intensity intervals on treadmill (Fitbit: −1.7% [SD 11.5]; Garmin: −0.5% [SD 9.4]). Fitbit and Garmin EE estimates differed significantly, with Garmin having less negative bias (Fitbit: −19.3% [SD 28.9], Garmin: −1.6% [SD 30.6], P<.001) across all activities, and with both correlating poorly with indirect calorimetry measures.ConclusionsTwo common wrist-worn devices (Fitbit Charge 2 and Garmin vívosmart HR+) show good HR accuracy, with a small negative bias, and reasonable EE estimates during low to moderate-intensity exercise and during a variety of common daily activities and exercise. Accuracy was compromised markedly when the activity indicator was not used on the watch or when activities involving less wrist motion such as cycle ergometry were done.

The addition of glucagon delivery to a closed-loop system with automated exercise detection reduces hypoglycemia in physically active adults with type 1 diabetes.

Aims Exercise increases risk of hypoglycemia in type 1 diabetes (T1D). An artificial pancreas (AP) can help mitigate this risk. We tested whether adjusting insulin and glucagon in response to exercise within a dual-hormone AP reduces exercise-related hypoglycemia. Materials and Methods In random order, 21 adults with T1D underwent three 22 h sessions: AP with exercise dosing adjustment (APX), AP with no exercise dosing adjustment (APN), and sensor-augmented pump therapy (SAP). After an overnight stay and 2 hours after breakfast, participants exercised for 45 minutes at 60% of their maximum heart rate with no snack given before exercise. During APX, insulin was decreased and glucagon was increased at exercise onset, while during SAP, subjects could adjust dosing before exercise. The two primary outcomes were percent of time in hypoglycemia (<3.9 mmol/L) and percent of time in euglycemia (3.9–10 mmol/L) from the start of exercise to the end of the study. Results The mean times spent in hypoglycemia (<3.9 mmol/L) after the start of exercise were 0.3% [−0.1, 0.7%] for APX, 3.1% [0.8, 5.3%] for APN, and 0.8% [0.1, 1.4%] for SAP. There was an absolute difference of 2.8% less time in hypoglycemia in APX versus APN (p =0.001) and 0.5% less time in hypoglycemia for APX versus SAP (p = 0.16). Mean time in euglycemia was comparable across conditions. Conclusions Adjusting insulin and glucagon delivery at exercise onset within a dual-hormone AP significantly reduces hypoglycemia compared with no adjustment and performs similarly to SAP when insulin is adjusted before exercise.

In this article, we present several important contributions necessary for enabling an artificial endocrine pancreas (AP) system to better respond to exercise events. First, we show how exercise can be automatically detected using body-worn accelerometer and heart rate sensors. During a 22 hour overnight inpatient study, 13 subjects with type 1 diabetes wearing a Zephyr accelerometer and heart rate monitor underwent 45 minutes of mild aerobic treadmill exercise while controlling their glucose levels using sensor-augmented pump therapy. We used the accelerometer and heart rate as inputs into a validated regression model. Using this model, we were able to detect the exercise event with a sensitivity of 97.2% and a specificity of 99.5%. Second, from this same study, we show how patients’ glucose declined during the exercise event and we present results from in silico modeling that demonstrate how including an exercise model in the glucoregulatory model improves the estimation of the drop in glucose during exercise. Last, we present an exercise dosing adjustment algorithm and describe parameter tuning and performance using an in silico glucoregulatory model during an exercise event.

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OBJECTIVEGlucagon delivery in closed-loop control of type 1 diabetes is effective in minimizing hypoglycemia. However, high insulin concentration lowers the hyperglycemic effect of glucagon, and small doses of glucagon in this setting are ineffective. There are no studies clearly defining the relationship between insulin levels, subcutaneous glucagon, and blood glucose.RESEARCH DESIGN AND METHODSUsing a euglycemic clamp technique in 11 subjects with type 1 diabetes, we examined endogenous glucose production (EGP) of glucagon (25, 75, 125, and 175 μg) at three insulin infusion rates (0.016, 0.032, and 0.05 units/kg/h) in a randomized, crossover study. Infused 6,6-dideuterated glucose was measured every 10 min, and EGP was determined using a validated glucoregulatory model. Area under the curve (AUC) for glucose production was the primary outcome, estimated over 60 min.RESULTSAt low insulin levels, EGP rose proportionately with glucagon dose, from 5 ± 68 to 112 ± 152 mg/kg (P = 0.038 linear trend), whereas at high levels, there was no increase in glucose output (19 ± 53 to 26 ± 38 mg/kg, P = NS). Peak glucagon serum levels and AUC correlated well with dose (r2 = 0.63, P < 0.001), as did insulin levels with insulin infusion rates (r2 = 0.59, P < 0.001).CONCLUSIONSEGP increases steeply with glucagon doses between 25 and 175 μg at lower insulin infusion rates. However, high insulin infusion rates prevent these doses of glucagon from significantly increasing glucose output and may reduce glucagon effectiveness in preventing hypoglycemia when used in the artificial pancreas.

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