Background: Accurate closed-loop control is essential for developing artificial pancreas (AP) systems that adjust insulin infusion rates from insulin pumps. Glucose concentration information from continuous glucose monitoring (CGM) systems is the most important information for the control system. Additional physiological measurements can provide valuable information that can enhance the accuracy of the control system. Proportional-integral-derivative control and model predictive control have been popular in AP development. Their implementations to date rely on meal announcements (e.g., bolus insulin dose based on insulin:carbohydrate ratios) by the user. Adaptive control techniques provide a powerful alternative that do not necessitate any meal or activity announcements. Materials and Methods: Adaptive control systems based on the generalized predictive control framework are developed by extending the recursive modeling techniques. Physiological signals such as energy expenditure and galvanic skin response are used along with glucose measurements to generate a multiple-input-single-output model for predicting future glucose concentrations used by the controller. Insulin-on-board (IOB) is also estimated and used in control decisions. The controllers were tested with clinical studies that include seven cases with three different patients with type 1 diabetes for 32 or 60 h without any meal or activity announcements. Results: The adaptive control system kept glucose concentration in the normal preprandial and postprandial range (70-180 mg/dL) without any meal or activity announcements during the test period. After IOB estimation was added to the control system, mild hypoglycemic episodes were observed only in one of the four experiments. This was reflected in a plasma glucose value of 56 mg/dL (YSI 2300 STAT; Yellow Springs Instrument, Yellow Springs, OH) and a CGM value of 63 mg/dL). Conclusions: Regulation of blood glucose concentration with an AP using adaptive control techniques was successful in clinical studies, even without any meal and physical activity announcement.

Background: Real-time continuous glucose monitoring (CGM) devices help detect glycemic excursions associated with exercise, meals, and insulin dosing in patients with type 1 diabetes (T1D). However, the delay between interstitial and blood glucose may result in CGM underestimating the true change in glycemia during activity. The purpose of this study was to examine CGM discrepancies during exercise and the meal postexercise versus self-monitoring of blood glucose (SMBG). Methods: Seventeen adults with T1D using insulin pump therapy and CGM completed 60 min of aerobic exercise on three occasions. A standardized meal was given 30 min postexercise. SMBG was measured during exercise and in recovery using OmniPod Ò Personal Diabetes Manager (PDM; Insulet, Billerica, MA) with builtin glucose meter (FreeStyle; Abbott Laboratories, Abbott Park, IL), while CGM was measured with Dexcom G4 Ò with 505 algorithm (n = 4) or G5 Ò (n = 13), which were calibrated with subjects' own PDM. Results: SMBG showed a large drop in glycemia during exercise, while CGM showed a lag of 12-11 (meanstandard deviation) minutes and bias of-7-19 mg/dL/min during activity. Mean absolute relative difference (MARD) for CGM versus SMBG was 13 (6-22)% [median (interquartile range)] during exercise and 8 (5-14)% during mealtime. Clarke error grids showed CGM values were in zones A and B 94%-99% of the time for SMBG. Conclusion: In summary, the drop in CGM lags behind the drop in blood glucose during prolonged aerobic exercise by 12-11 min, and MARD increases to 13 (6-22)% during exercise as well. Therefore, if hypoglycemia is suspected during exercise, individuals should confirm glucose levels with a capillary glucose measurement.

A constrained weighted recursive least squares method is proposed to provide recursive models with guaranteed stability and better performance than models based on regular identification methods in predicting the variations of blood glucose concentration in patients with Type 1 Diabetes. Use of physiological information from a sports armband improves glucose concentration prediction and enables earlier recognition of the effects of physical activity on glucose concentration. Generalized predictive controllers (GPC) based on these recursive models are developed. The performance of GPC for artificial pancreas systems is illustrated by simulations with UVa-Padova simulator and clinical studies. The controllers developed are good candidates for artificial pancreas systems with no announcements from patients.

A novel meal-detection algorithm is developed based on continuous glucose measurements. Bergman’s minimal model is modified and used in an unscented Kalman filter for state estimations. The estimated rate of appearance of glucose is used for meal detection. Data from nine subjects are used to assess the performance of the algorithm. The results indicate that the proposed algorithm works successfully with high accuracy. The average change in glucose levels between the meals and the detection points is 16(±9.42) [mg/dl] for 61 successfully detected meals and snacks. The algorithm is developed as a new module of an integrated multivariable adaptive artificial pancreas control system. Meal detection with the proposed method is used to administer insulin boluses and prevent most of post-prandial hyperglycemia without any manual meal announcements. A novel meal bolus calculation method is proposed and tested with the UVA/Padova simulator. The results indicate significant reduction in hyperglycemia.

Hypoglycemia is a major challenge of artificial pancreas systems and a source of concern for potential users and parents of young children with Type 1 diabetes (T1D). Early alarms to warn the potential of hypoglycemia are essential and should provide enough time to take action to avoid hypoglycemia. Many alarm systems proposed in the literature are based on interpretation of recent trends in glucose values. In the present study, subject-specific recursive linear time series models are introduced as a better alternative to capture glucose variations and predict future blood glucose concentrations. These models are then used in hypoglycemia early alarm systems that notify patients to take action to prevent hypoglycemia before it happens. The models developed and the hypoglycemia alarm system are tested retrospectively using T1D subject data. A Savitzky-Golay filter and a Kalman filter are used to reduce noise in patient data. The hypoglycemia alarm algorithm is developed by using predictions of future glucose concentrations from recursive models. The modeling algorithm enables the dynamic adaptation of models to inter-/intra-subject variation and glycemic disturbances and provides satisfactory glucose concentration prediction with relatively small error. The alarm systems demonstrate good performance in prediction of hypoglycemia and ultimately in prevention of its occurrence.