Concordance of Blood Glucose and CGM During a Pilot Trial of Automated Insulin Delivery in Type 1 Diabetes Pregnancies.

Background: Customized and standard automated insulin delivery (AID) systems for use in pregnancies of women with preexisting type 1 diabetes (T1D) are being developed and tested to achieve pregnancy appropriate continuous glucose monitoring (CGM) targets. Guidance on the use of CGM for treatment decisions during pregnancy in the United States is limited. Methods: Ten pregnant women with preexisting T1D participated in a trial evaluating at-home use of a pregnancy-specific AID system. Seven-point self-monitoring of blood glucose (SMBG) was compared to the closest sensor glucose (Dexcom G6 CGM) value biweekly to assess safety and reliability based on the 20%/20 mg/dL criteria. Results: All participants completed the study with 7 participants satisfying the safety and reliability criteria with a mean absolute relative difference of 10.3%. Three participants did not fulfill the criteria, mainly because the frequency of SMBG did not meet the requirements. Conclusion: Dexcom G6 CGM is safe and accurate in the real-world setting for use in pregnant women with preexisting T1D with reduced SMBG testing as part of a pregnancy-specific AID system.

At-Home Use of a Pregnancy-Specific Zone-MPC Closed-Loop System for Pregnancies Complicated by Type 1 Diabetes: A Single-Arm, Observational Multicenter Study.

OBJECTIVE: There are no commercially available hybrid closed-loop insulin delivery systems customized to achieve pregnancy-specific glucose targets in the U.S. This study aimed to evaluate the feasibility and performance of at-home use of a zone model predictive controller-based closed-loop insulin delivery system customized for pregnancies complicated by type 1 diabetes (CLC-P). RESEARCH DESIGN AND METHODS: Pregnant women with type 1 diabetes using insulin pumps were enrolled in the second or early third trimester. After study sensor wear collecting run-in data on personal pump therapy and 2 days of supervised training, participants used CLC-P targeting 80-110 mg/dL during the day and 80-100 mg/dL overnight running on an unlocked smartphone at home. Meals and activities were unrestricted throughout the trial. The primary outcome was the continuous glucose monitoring percentage of time in the target range 63-140 mg/dL versus run-in. RESULTS: Ten participants (HbA1c 5.8 ± 0.6%) used the system from mean gestational age of 23.7 ± 3.5 weeks. Mean percentage time in range increased 14.1 percentage points, equivalent to 3.4 h per day, compared with run-in (run-in 64.5 ± 16.3% versus CLC-P 78.6 ± 9.2%; P = 0.002). During CLC-P use, there was significant decrease in both time over 140 mg/dL (P = 0.033) and the hypoglycemic ranges of less than 63 mg/dL and 54 mg/dL (P = 0.037 for both). Nine participants exceeded consensus goals of above 70% time in range during CLC-P use. CONCLUSIONS: The results show that the extended use of CLC-P at home until delivery is feasible. Larger, randomized studies are needed to further evaluate system efficacy and pregnancy outcomes.

Design of a Real-Time Physical Activity Detection and Classification Framework for Individuals With Type 1 Diabetes.

BACKGROUND: Managing glycemia during and after exercise events in type 1 diabetes (T1D) is challenging since these events can have wide-ranging effects on glycemia depending on the event timing, type, intensity. To this end, advanced physical activity-informed technologies can be beneficial for improving glucose control. METHODS: We propose a real-time physical activity detection and classification framework, which builds upon random forest models. This module automatically detects exercise sessions and predicts the activity type and intensity from tri-axial accelerometer, heart rate, and continuous glucose monitoring records. RESULTS: Data from 19 adults with T1D who performed structured sessions of either aerobic, resistance, or high-intensity interval exercise at varying times of day were used to train and test this framework. The exercise onset and completion were both predicted within 1 minute with an average accuracy of 81% and 78%, respectively. Activity type and intensity were identified within 2.38 minutes and from the exercise onset. On participants assigned to the test set, the average accuracy for activity type and intensity classification was 74% and 73%, respectively, if exercise was announced. For unannounced exercise events, the classification accuracy was 65% for the activity type and 70% for its intensity. CONCLUSIONS: The proposed module showed high performance in detection and classification of exercise in real-time within a minute of exercise onset. Integration of this module into insulin therapy decisions can help facilitate glucose management around physical activity.

Feasibility of Closed-Loop Insulin Delivery with a Pregnancy-Specific Zone Model Predictive Control Algorithm.

Objective: Evaluating the feasibility of closed-loop insulin delivery with a zone model predictive control (zone-MPC) algorithm designed for pregnancy complicated by type 1 diabetes (T1D). Research Design and Methods: Pregnant women with T1D from 14 to 32 weeks gestation already using continuous glucose monitor (CGM) augmented pump therapy were enrolled in a 2-day multicenter supervised outpatient study evaluating pregnancy-specific zone-MPC based closed-loop control (CLC) with the interoperable artificial pancreas system (iAPS) running on an unlocked smartphone. Meals and activities were unrestricted. The primary outcome was the CGM percentage of time between 63 and 140 mg/dL compared with participants' 1-week run-in period. Early (2-h) postprandial glucose control was also evaluated. Results: Eleven participants completed the study (age: 30.6 ± 4.1 years; gestational age: 20.7 ± 3.5 weeks; weight: 76.5 ± 15.3 kg; hemoglobin A1c: 5.6% ± 0.5% at enrollment). No serious adverse events occurred. Compared with the 1-week run-in, there was an increased percentage of time in 63-140 mg/dL during supervised CLC (CLC: 81.5%, run-in: 64%, P = 0.007) with less time >140 mg/dL (CLC: 16.5%, run-in: 30.8%, P = 0.029) and time <63 mg/dL (CLC: 2.0%, run-in:5.2%, P = 0.039). There was also less time <54 mg/dL (CLC: 0.7%, run-in:1.6%, P = 0.030) and >180 mg/dL (CLC: 4.9%, run-in: 13.1%, P = 0.032). Overnight glucose control was comparable, except for less time >250 mg/dL (CLC: 0%, run-in:3.9%, P = 0.030) and lower glucose standard deviation (CLC: 23.8 mg/dL, run-in:42.8 mg/dL, P = 0.007) during CLC. Conclusion: In this pilot study, use of the pregnancy-specific zone-MPC was feasible in pregnant women with T1D. Although the duration of our study was short and the number of participants was small, our findings add to the limited data available on the use of CLC systems during pregnancy (NCT04492566).

Hypoglycemia in Prospective Multicenter Study of Pregnancies with Pre-Existing Type 1 Diabetes on Sensor-Augmented Pump Therapy: The LOIS-P Study.

Background: Pregnancies in type 1 diabetes are high risk, and data in the United States are limited regarding continuous glucose monitoring (CGM)-based hypoglycemia throughout pregnancy while on sensor-augmented insulin pump therapy. Materials and Methods: Pregnant women with type 1 diabetes in the LOIS-P Study (Longitudinal Observation of Insulin use and glucose Sensor metrics in Pregnant women with type 1 diabetes using continuous glucose monitors and insulin pumps) were enrolled before 17 weeks gestation at three U.S. centers and we used their personal insulin pump and a study Dexcom G6 CGM. We analyzed data of 25 pregnant women for CGM hypoglycemia based on international consensus guidelines for percentage time <63 and 54 mg/dL, hypoglycemic events and prolonged hypoglycemia events for 24-h, daytime, and overnight periods, and severe hypoglycemia (SH) episodes. Results: For a 24-h period, biweekly median percentage of time <63 mg/dL ranged from 0.8% at biweek 4-5 to 3.7% at biweek 14-15 with high variability throughout pregnancy. Median percentage of time <63 and 54 mg/dL was higher overnight than daytime (P < 0.01). Hypoglycemic events occurred throughout the pregnancy, ranged 1-4 events per 2 weeks, significantly decreased after the 20th week, and occurred predominantly during daytime (P < 0.01). For overnight period, hypoglycemia and events were more concentrated from 12 to 3 am. Seven prolonged hypoglycemia events without any associated SH occurred in four participants (16%), primarily overnight. Three participants experienced a single episode of SH. Conclusions: Our results suggest a higher overall risk of hypoglycemia throughout pregnancy during the overnight period with continued daytime risk of hypoglycemic events in pregnancies complicated by type 1 diabetes.

Safety and Feasibility Evaluation of Step Count Informed Meal Boluses in Type 1 Diabetes: A Pilot Study.

BACKGROUND: Physical activity can cause glucose fluctuations both during and after it is performed, leading to hurdles in optimal insulin dosing in people with type 1 diabetes (T1D). We conducted a pilot clinical trial assessing the safety and feasibility of a physical activity-informed mealtime insulin bolus advisor that adjusts the meal bolus according to previous physical activity, based on step count data collected through an off-the-shelf physical activity tracker. METHODS: Fifteen adults with T1D, each using a continuous glucose monitor (CGM) and an insulin pump with carbohydrate counting, completed two randomized crossover daily visits. Participants performed a 30 to 45-minute brisk walk before lunch and lunchtime insulin boluses were calculated based on either their standard therapy (ST) or the physical activity-informed bolus method. Post-lunch glycemic excursions were assessed using CGM readings. RESULTS: There was no significant difference between visits in the time spent in hypoglycemia in the post-lunch period (median [IQR] standard: 0 [0]% vs physical activity-informed: 0 [0]%, P = NS). Standard therapy bolus yielded a higher time spent in 70 to 180 mg/dL target range (mean ± standard: 77% ± 27% vs physical activity-informed: 59% ± 31%, P = .03) yet, it was associated with a steeper negative slope in the early postprandial phase (P = .032). CONCLUSIONS: Use of step count to adjust mealtime insulin following a walking bout has proved to be safe and feasible in a cohort of 15 T1D subjects. Physical activity-informed insulin dosing of meals eaten soon after a walking bout has a potential of mitigating physical activity related glucose reduction in the early postprandial phase.

Review of Automated Insulin Delivery Systems for Individuals with Type 1 Diabetes: Tailored Solutions for Subpopulations.

Automated insulin delivery (AID) systems have proven safe and effective in improving glycemic outcomes in individuals with type 1 diabetes (T1D). Clinical evaluation of this technology has progressed to large randomized, controlled outpatient studies and recent commercial approval of AID systems for children and adults. However, several challenges remain in improving these systems for different subpopulations (e.g., young children, athletes, pregnant women, seniors and those with hypoglycemia unawareness). In this review, we highlight the requirements and challenges in AID design for selected subpopulations, and discuss current advances from recent clinical studies.

Longitudinal Observation of Insulin Use and Glucose Sensor Metrics in Pregnant Women with Type 1 Diabetes Using Continuous Glucose Monitors and Insulin Pumps: The LOIS-P Study.

Background: Suboptimal glycemic control is associated with maternal and neonatal morbidity and mortality in pregnancy complicated by type 1 diabetes (T1D). Prospective analysis of continuous glucose monitoring (CGM) metrics, insulin pump settings, and insulin delivery can better characterize the changes in glycemic levels and insulin use throughout pregnancy with T1D. Materials and Methods: Prescribed parameters, insulin delivery, carbohydrate intake, and CGM data for 25 pregnant women with T1D from three U.S. sites were collected. Participants enrolled before 17 weeks gestation and used personal insulin pumps and study CGM. Mean daily total, basal, and bolus insulin doses (units/kg), CGM time in range (TIR: 63-140 mg/dL), and pump-entered carbohydrates were analyzed for every 2-week gestational interval. Linear mixed-effects regression models were used to evaluate changes across gestational ages compared to 12-14 weeks. Results: Basal insulin was higher during weeks 6-12 and 24-40. Daily bolus and total insulin were higher during weeks 20-40. Pump parameters were adjusted to intensify insulin therapy from 22 weeks onward. Average TIR across pregnancy was 59% ± 14%. Between 18 and 30 weeks, TIR was significantly lower, and time above range was significantly higher compared to the reference biweek. Time below target was lower between 22 and 34 weeks. Seven participants achieved >70% recommended TIR for pregnancy. Participants with maternal complications or infant neonatal intensive care unit admissions had lower TIR. Conclusion: While insulin dosing changed significantly with advancing gestation, most participants did not achieve >70% TIR. Customized anticipatory pump setting adjustments and automated systems aimed toward the designated TIR are needed to improve outcomes for this population. NCT03761615.

Anticipation of Historical Exercise Patterns by a Novel Artificial Pancreas System Reduces Hypoglycemia During and After Moderate-Intensity Physical Activity in People with Type 1 Diabetes.

Objective: Physical activity is a major challenge to glycemic control for people with type 1 diabetes. Moderate-intensity exercise often leads to steep decreases in blood glucose and hypoglycemia that closed-loop control systems have so far failed to protect against, despite improving glycemic control overall. Research Design and Methods: Fifteen adults with type 1 diabetes (42 ± 13.5 years old; hemoglobin A1c 6.6% ± 1.0%; 10F/5M) participated in a randomized crossover clinical trial comparing two hybrid closed-loop (HCL) systems, a state-of-the-art hybrid model predictive controller and a modified system designed to anticipate and detect unannounced exercise (APEX), during two 32-h supervised admissions with 45 min of planned moderate activity, following 4 weeks of data collection. Primary outcome was the number of hypoglycemic episodes during exercise. Continuous glucose monitor (CGM)-based metrics and hypoglycemia are also reported across the entire admissions. Results: The APEX system reduced hypoglycemic episodes overall (9 vs. 33; P = 0.02), during exercise (5 vs. 13; P = 0.04), and in the 4 h following (2 vs. 11; P = 0.02). Overall CGM median percent time <70 mg/dL decreased as well (0.3% vs. 1.6%; P = 0.004). This protection was obtained with no significant increase in time >180 mg/dL (18.5% vs. 16.6%, P = 0.15). Overnight control was notable for both systems with no hypoglycemia, median percent in time 70-180 mg/dL at 100% and median percent time 70-140 mg/dL at ∼96% for both. Conclusions: A new closed-loop system capable of anticipating and detecting exercise was proven to be safe and feasible and outperformed a state-of-the-art HCL, reducing participants' exposure to hypoglycemia during and after moderate-intensity physical activity. ClinicalTrials.gov NCT03859401.

Zone-MPC Automated Insulin Delivery Algorithm Tuned for Pregnancy Complicated by Type 1 Diabetes.

Type 1 diabetes (T1D) increases the risk for pregnancy complications. Increased time in the pregnancy glucose target range (63-140 mg/dL as suggested by clinical guidelines) is associated with improved pregnancy outcomes that underscores the need for tight glycemic control. While closed-loop control is highly effective in regulating blood glucose levels in individuals with T1D, its use during pregnancy requires adjustments to meet the tight glycemic control and changing insulin requirements with advancing gestation. In this paper, we tailor a zone model predictive controller (zone-MPC), an optimization-based control strategy that uses model predictions, for use during pregnancy and verify its robustness in-silico through a broad range of scenarios. We customize the existing zone-MPC to satisfy pregnancy-specific glucose control objectives by having (i) lower target glycemic zones (i.e., 80-110 mg/dL daytime and 80-100 mg/dL overnight), (ii) more assertive correction bolus for hyperglycemia, and (iii) a control strategy that results in more aggressive postprandial insulin delivery to keep glucose within the target zone. The emphasis is on leveraging the flexible design of zone-MPC to obtain a controller that satisfies glycemic outcomes recommended for pregnancy based on clinical insight. To verify this pregnancy-specific zone-MPC design, we use the UVA/Padova simulator and conduct in-silico experiments on 10 subjects over 13 scenarios ranging from scenarios with ideal metabolic and treatment parameters for pregnancy to extreme scenarios with such parameters that are highly deviant from the ideal. All scenarios had three meals per day and each meal had 40 grams of carbohydrates. Across 13 scenarios, pregnancy-specific zone-MPC led to a 10.3 ± 5.3% increase in the time in pregnancy target range (baseline zone-MPC: 70.6 ± 15.0%, pregnancy-specific zone-MPC: 80.8 ± 11.3%, p < 0.001) and a 10.7 ± 4.8% reduction in the time above the target range (baseline zone-MPC: 29.0 ± 15.4%, pregnancy-specific zone-MPC: 18.3 ± 12.0, p < 0.001). There was no significant difference in the time below range between the controllers (baseline zone-MPC: 0.5 ± 1.2%, pregnancy-specific zone-MPC: 3.5 ± 1.9%, p = 0.1). The extensive simulation results show improved performance in the pregnancy target range with pregnancy-specific zone MPC, suggest robustness of the zone-MPC in tight glucose control scenarios, and emphasize the need for customized glucose control systems for pregnancy.

Automatically accounting for physical activity in insulin dosing for type 1 diabetes.

BACKGROUND AND OBJECTIVE: Type 1 diabetes is a disease characterized by lifelong insulin administration to compensate for the autoimmune destruction of insulin-producing pancreatic beta-cells. Optimal insulin dosing presents a challenge for individuals with type 1 diabetes, as the amount of insulin needed for optimal blood glucose control depends on each subject's varying needs. In this context, physical activity represents one of the main factors altering insulin requirements and complicating treatment decisions. This work aims to develop and test in simulation a data-driven method to automatically incorporate physical activity into daily treatment decisions to optimize mealtime glycemic control in individuals with type 1 diabetes. METHODS: We leveraged glucose, insulin, meal and physical activity data collected from twenty-three individuals to develop a method that (i) tracks and quantifies the accumulated glycemic impact from daily physical activity in real-time, (ii) extracts an individualized routine physical activity profile, and (iii) adjusts insulin doses according to the prolonged changes in insulin needs due to deviations in daily physical activity in a personalized manner. We used the data replay simulation framework developed at the University of Virginia to "re-simulate" the clinical data and estimate the performances of the new decision support system for physical activity informed insulin dosing against standard insulin dosing. The paired t-test is used to compare the performances of dosing methods with p < 0.05 as the significance threshold. RESULTS: Simulation results show that, compared with standard dosing, the proposed physical-activity informed insulin dosing could result in significantly less time spent in hypoglycemia (15.3± 8% vs. 11.1± 4%, p = 0.007) and higher time spent in the target glycemic range (66.1± 11.7% vs. 69.6± 12.2%, p < 0.01) and no significant difference in the time spent above the target range(26.6± 1.4 vs. 27.4± 0.1, p = 0.5). CONCLUSIONS: Integrating daily physical activity, as measured by the step count, into insulin dose calculations has the potential to improve blood glucose control in daily life with type 1 diabetes.

Impact of Daily Physical Activity as Measured by Commonly Available Wearables on Mealtime Glucose Control in Type 1 Diabetes.

Objective: In contrast with exercise, or structured physical activity (PA), glycemic disturbances due to daily unstructured PA in patients with type 1 diabetes (T1D) is largely underresearched, with limited information on treatment recommendations. We present results from retrospective analysis of data collected under patients' free-living conditions that illuminate the association between PA, as measured by an off-the-shelf activity tracker, and postprandial blood glucose control. Research Design and Methods: Data from 37 patients with T1D during two clinical studies with identical data collection protocols were analyzed retrospectively: 4 weeks of continuous glucose monitoring, carbohydrate intake, insulin injections, and PA (assessed through wearable activity tracker) were collected in free-living conditions. Five-hour glucose area under curves (GAUCs) following the last-bolused meal of every day were computed to assess postprandial glucose excursions, and their relation with corresponding antecedent PA was analyzed using linear mixed-effects regression models, accounting for meal, insulin, and current glycemic state. Results: Datasets yielded 845 days of data from 37 subjects (22.8 ± 11.6 days/subject); postmeal GAUC was negatively associated with total daily PA measured by step count (P = 0.025), and total time spent performing higher than light-intensity PA (P = 0.042). Patients with higher median total daily PA exhibited lower average postprandial GAUC (P < 0.01). Additional analyses indicated that daily PA likely presents an immediate and delayed impact on glucose control. Conclusion: Daily PA assessed by commonly available sensors is significantly associated with glycemic exposure after an evening meal, indicating that quantitative assessment of PA may be useful in mealtime treatment decisions.

Continuous Glucose Monitors and Activity Trackers to Inform Insulin Dosing in Type 1 Diabetes: The University of Virginia Contribution.

Objective: Suboptimal insulin dosing in type 1 diabetes (T1D) is frequently associated with time-varying insulin requirements driven by various psycho-behavioral and physiological factors influencing insulin sensitivity (IS). Among these, physical activity has been widely recognized as a trigger of altered IS both during and following the exercise effort, but limited indication is available for the management of structured and (even more) unstructured activity in T1D. In this work, we present two methods to inform insulin dosing with biosignals from wearable sensors to improve glycemic control in individuals with T1D. Research Design and Methods: Continuous glucose monitors (CGM) and activity trackers are leveraged by the methods. The first method uses CGM records to estimate IS in real time and adjust the insulin dose according to a person's insulin needs; the second method uses step count data to inform the bolus calculation with the residual glucose-lowering effects of recently performed (structured or unstructured) physical activity. The methods were tested in silico within the University of Virginia/Padova T1D Simulator. A standard bolus calculator and the proposed "smart" systems were deployed in the control of one meal in presence of increased/decreased IS (Study 1) and following a 1-hour exercise bout (Study 2). Postprandial glycemic control was assessed in terms of time spent in different glycemic ranges and low/high blood glucose indices (LBGI/HBGI), and compared between the dosing strategies. Results: In Study 1, the CGM-informed system allowed to reduce exposure to hypoglycemia in presence of increased IS (percent time < 70 mg/dL: 6.1% versus 9.9%; LBGI: 1.9 versus 3.2) and exposure to hyperglycemia in presence of decreased IS (percent time > 180 mg/dL: 14.6% versus 18.3%; HBGI: 3.0 versus 3.9), tending toward optimal control. In Study 2, the step count-informed system allowed to reduce hypoglycemia (percent time < 70 mg/dL: 3.9% versus 13.4%; LBGI: 1.7 versus 3.2) at the cost of a minor increase in exposure to hyperglycemia (percent time > 180 mg/dL: 11.9% versus 7.5%; HBGI: 2.4 versus 1.5). Conclusions: We presented and validated in silico two methods for the smart dosing of prandial insulin in T1D. If seen within an ensemble, the two algorithms provide alternatives to individuals with T1D for improving insulin dosing accommodating a large variety of treatment options. Future work will be devoted to test the safety and efficacy of the methods in free-living conditions.

In Silico Analysis of an Exercise-Safe Artificial Pancreas With Multistage Model Predictive Control and Insulin Safety System.

BACKGROUND: Maintaining glycemic equilibrium can be challenging for people living with type 1 diabetes (T1D) as many factors (eg, length, type, duration, insulin on board, stress, and training) will impact the metabolic changes triggered by physical activity potentially leading to both hypoglycemia and hyperglycemia. Therefore, and despite the noted health benefits, many individuals with T1D do not exercise as much as their healthy peers. While technology advances have improved glucose control during and immediately after exercise, it remains one of the key limitations of artificial pancreas (AP) systems, largely because stopping insulin at the onset of exercise may not be enough to prevent impending, exercise-induced hypoglycemia. METHODS: A hybrid AP algorithm with subject-specific exercise behavior recognition and anticipatory action is designed to prevent hypoglycemic events during and after moderate-intensity exercise. Our approach relies on a number of key innovations, namely, an activity informed premeal bolus calculator, personalized exercise pattern recognition, and a multistage model predictive control (MS-MPC) strategy that can transition between reactive and anticipatory modes. This AP design was evaluated on 100 in silico subjects from the most up-to-date FDA-accepted UVA/Padova metabolic simulator, emulating an outpatient clinical trial setting. Results with a baseline controller, a regular MPC (rMPC), are also included for comparison purposes. RESULTS: In silico experiments reveal that the proposed MS-MPC strategy markedly reduces the number of exercise-related hypoglycemic events (8 vs 68). CONCLUSION: An anticipatory mode for insulin administration of a monohormonal AP controller reduces the occurrence of hypoglycemia during moderate-intensity exercise.

Body Mass Index Effect on Differing Responses to Psychological Stress in Blood Glucose Dynamics in Patients With Type 1 Diabetes.

OBJECTIVE: The objective was to investigate the relationship of body mass index (BMI) to differing glycemic responses to psychological stress in patients with type 1 diabetes. METHODS: Continuous blood glucose monitor (CGM) data were collected for 1 week from a total of 37 patients with BMI ranging from 21.5-39.4 kg/m2 (mean = 28.2 ± 4.9). Patients reported daily stress levels (5-point Likert-type scale, 0 = none, 4 = extreme), physical activity, carbohydrate intake, insulin boluses and basal rates. Daily reported carbohydrates, total insulin bolus, and average blood glucose (BG from CGM) were compared among patients based on their BMI levels on days with different stress levels. In addition, daily averages of a model-based "effectiveness index" (quantifying the combined impact of insulin and carbohydrate on glucose levels) were defined and compared across stress levels to capture meal and insulin independent glycemic changes. RESULTS: Analyses showed that patient BMI likely moderated stress related glycemic changes. Linear mixed effect model results were significant for the stress-BMI interaction on both behavioral and behavior-independent glycemic changes. Across participants, under stress, an increase was observed in daily carbohydrate intake and effectiveness index at higher BMI. There was no significant interactive effect on daily insulin or average BG. CONCLUSION: Findings suggest that (1) stress has both behavioral and nonbehavioral glycemic effects on T1D patients and (2) the direction and magnitude of these effects are potentially influenced by level of stress and patient BMI. Possibly responsible for these observed effects are T1D/BMI related alterations in endocrine response.