Neural-Net Artificial Pancreas: A Randomized Crossover Trial of a First-in-Class Automated Insulin Delivery Algorithm.

BACKGROUND: Automated Insulin Delivery (AID) is now integral to the clinical practice of Type 1 diabetes (T1D). The objective of this pilot-feasibility study was to introduce a new regulatory and clinical paradigm - a Neural-Net Artificial Pancreas (NAP) - an encoding of an AID algorithm into a neural network that approximates its action, and assess NAP vs the original AID algorithm. METHODS: The UVA model-predictive control (UMPC) algorithm was encoded into a neural network, creating its NAP approximation. Seventeen AID users with T1D were recruited and 15 participated in two consecutive 20-hour hotel sessions, receiving in random order either NAP or UMPC. Their demographic characteristics were: ages 22-68 years old, duration of diabetes 7-58 years, gender 10/5 female/male, White Non-Hispanic/Black 13/2, and baseline HbA1c 5.4-8.1%. RESULTS: The time-in-range (TIR) difference between NAP and UMPC, adjusted for entry glucose level, was 1 percentage point, with absolute TIR values of 86% (NAP) and 87% (UMPC). The two algorithms achieved similar times <70 mg/dL of 2.0% vs 1.8% and coefficients of variation of 29.3% (NAP) vs 29.1 (UMPC)%. Under identical inputs, the average absolute insulin-recommendation difference was 0.031 units/hour. There were no serious adverse events on either controller. NAP had 6-fold lower computational demands than UMPC. CONCLUSION: In a randomized crossover study, a neural-network encoding of a complex model-predictive control algorithm demonstrated similar performance, at a fraction of the computational demands. Regulatory and clinical doors are therefore open for contemporary machine learning methods to enter the AID field.

Safety and Efficacy of Sustained Automated Insulin Delivery Compared With Sensor and Pump Therapy in Adults With Type 1 Diabetes at High Risk for Hypoglycemia: A Randomized Controlled Trial.

OBJECTIVE: Assess the safety and efficacy of automated insulin delivery (AID) in adults with type 1 diabetes (T1D) at high risk for hypoglycemia. RESEARCH DESIGN AND METHODS: Participants were 72 adults with T1D who used an insulin pump with Clarke Hypoglycemia Perception Awareness scale score >3 and/or had severe hypoglycemia during the previous 6 months confirmed by time below range (TBR; defined as sensor glucose [SG] reading <70 mg/dL) of at least 5% during 2 weeks of blinded continuous glucose monitoring (CGM). Parallel-arm, randomized trial (2:1) of AID (Tandem t:slim ×2 with Control-IQ technology) versus CGM and pump therapy for 12 weeks. The primary outcome was TBR change from baseline. Secondary outcomes included time in target range (TIR; 70-180 mg/dL), time above range (TAR), mean SG reading, and time with glucose level <54 mg/dL. An optional 12-week extension with AID was offered to all participants. RESULTS: Compared with the sensor and pump (S&P), AID resulted in significant reduction of TBR by -3.7% (95% CI -4.8, -2.6), P < 0.001; an 8.6% increase in TIR (95% CI 5.2, 12.1), P < 0.001; and a -5.3% decrease in TAR (95% CI -87.7, -1.8), P = 0.004. Mean SG reading remained similar in the AID and S&P groups. During the 12-week extension, the effects of AID were sustained in the AID group and reproduced in the S&P group. Two severe hypoglycemic episodes occurred using AID. CONCLUSIONS: In adults with T1D at high risk for hypoglycemia, AID reduced the risk for hypoglycemia more than twofold, as quantified by TBR, while improving TIR and reducing hyperglycemia. Hence, AID is strongly recommended for this specific population.

Consensus Recommendations for the Use of Automated Insulin Delivery Technologies in Clinical Practice.

The significant and growing global prevalence of diabetes continues to challenge people with diabetes (PwD), healthcare providers, and payers. While maintaining near-normal glucose levels has been shown to prevent or delay the progression of the long-term complications of diabetes, a significant proportion of PwD are not attaining their glycemic goals. During the past 6 years, we have seen tremendous advances in automated insulin delivery (AID) technologies. Numerous randomized controlled trials and real-world studies have shown that the use of AID systems is safe and effective in helping PwD achieve their long-term glycemic goals while reducing hypoglycemia risk. Thus, AID systems have recently become an integral part of diabetes management. However, recommendations for using AID systems in clinical settings have been lacking. Such guided recommendations are critical for AID success and acceptance. All clinicians working with PwD need to become familiar with the available systems in order to eliminate disparities in diabetes quality of care. This report provides much-needed guidance for clinicians who are interested in utilizing AIDs and presents a comprehensive listing of the evidence payers should consider when determining eligibility criteria for AID insurance coverage.

Biobehavioral Changes Following Transition to Automated Insulin Delivery: A Large Real-life Database Analysis.

OBJECTIVE: To document glycemic and user-initiated bolus changes following transition from predictive low glucose suspend (PLGS) system to automated insulin delivery (AID) system during real-life use. RESEARCH DESIGN AND METHODS: We conducted analysis of 2,329,166 days (6,381 patient-years) of continuous glucose monitoring (CGM) and insulin therapy data for 19,354 individuals with type 1 Diabetes, during 1-month PLGS use (Basal-IQ technology) followed by 3-month AID use (Control-IQ technology). Baseline characteristics are as follows: 55.4% female, age (median/quartiles/range) 39/19-58/1-92 years, mean ± SD glucose management indicator (GMI) 7.5 ± 0.8. Primary outcome was time in target range (TIR) (70-180 mg/dL). Secondary outcomes included CGM-based glycemic control metrics and frequency of user-initiated boluses. RESULTS: Compared with PLGS, AID increased TIR on average from 58.4 to 70.5%. GMI and percent time above and below target range improved as well: from 7.5 to 7.1, 39.9 to 28.1%, and 1.66 to 1.46%, respectively; all P values <0.0001. Stratification of outcomes by age and baseline GMI revealed clinically significant differences. Glycemic improvements were most pronounced in those <18 years old (TIR improvement 14.0 percentage points) and those with baseline GMI >8.0 (TIR improvement 13.2 percentage points). User-initiated correction boluses decreased from 2.7 to 1.8 per day, while user-initiated meal boluses remained stable at 3.6 to 3.8 per day. CONCLUSIONS: Observed in real life of >19,000 individuals with type 1 diabetes, transitions from PLGS to AID resulted in improvement of all glycemic parameters, equivalent to improvements observed in randomized clinical trials, and reduced user-initiated boluses. However, glycemic and behavioral changes with AID use may differ greatly across different demographic and clinical groups.

External validation of a classifier of daily continuous glucose monitoring (CGM) profiles.

As continuous glucose monitoring (CGM) sensors generate ever increasing amounts of CGM data, the need for methods to simplify the storage and analysis of this data becomes increasingly important. Lobo et al. developed a classifier of daily CGM profiles as an initial step in addressing this need. The classifier has several important applications including, but not limited to, data compression, data encryption, and indexing of databases. While the classifier has already successfully classified 99.0% of the 42,595 daily CGM profiles in a Test Set, this work presents an external validation using an external validation set (EVal Set) derived from 8 publicly available data sets. The Test Set and the EVal Set differ in terms of (but not limited to) demographics, data collection time periods, and data collection geographies. The classifier successfully classified 98.2% of the 137,030 daily CGM profiles in the EVal Set. Furthermore, each of the 483 distinct groups of classified daily CGM profiles from the EVal Set retains the same clinical characteristics as the corresponding group from the Test Set, as desired. Finally, the set of unclassified daily CGM profiles from the EVal Set retains the same statistical characteristics as the set of unclassified daily CGM profiles from the Test Set, as desired. These results establish the robustness and generalizability of the classifier: the performance of the classifier is unchanged despite the marked differences between the Test Set and the EVal Set.

Patient-Reported Outcomes in a Randomized Trial of Closed-Loop Control: The Pivotal International Diabetes Closed-Loop Trial.

Background: Closed-loop control (CLC) has been shown to improve glucose time in range and other glucose metrics; however, randomized trials >3 months comparing CLC with sensor-augmented pump (SAP) therapy are limited. We recently reported glucose control outcomes from the 6-month international Diabetes Closed-Loop (iDCL) trial; we now report patient-reported outcomes (PROs) in this iDCL trial. Methods: Participants were randomized 2:1 to CLC (N = 112) versus SAP (N = 56) and completed questionnaires, including Hypoglycemia Fear Survey, Diabetes Distress Scale (DDS), Hypoglycemia Awareness, Hypoglycemia Confidence, Hyperglycemia Avoidance, and Positive Expectancies of CLC (INSPIRE) at baseline, 3, and 6 months. CLC participants also completed Diabetes Technology Expectations and Acceptance and System Usability Scale (SUS). Results: The Hypoglycemia Fear Survey Behavior subscale improved significantly after 6 months of CLC compared with SAP. DDS did not differ except for powerless subscale scores, which worsened at 3 months in SAP. Whereas Hypoglycemia Awareness and Hyperglycemia Avoidance did not differ between groups, CLC participants showed a tendency toward improved confidence in managing hypoglycemia. The INSPIRE questionnaire showed favorable scores in the CLC group for teens and parents, with a similar trend for adults. At baseline and 6 months, CLC participants had high positive expectations for the device with Diabetes Technology Acceptance and SUS showing high benefit and low burden scores. Conclusion: CLC improved some PROs compared with SAP. Participants reported high benefit and low burden with CLC. Clinical Trial Identifier: NCT03563313.

One Year Real-World Use of the Control-IQ Advanced Hybrid Closed-Loop Technology.

Background: The t:slim X2™ insulin pump with Control-IQ® technology from Tandem Diabetes Care is an advanced hybrid closed-loop system that was first commercialized in the United States in January 2020. Longitudinal glycemic outcomes associated with real-world use of this system have yet to be reported. Methods: A retrospective analysis of Control-IQ technology users who uploaded data to Tandem's t:connect® web application as of February 11, 2021 was performed. Users age ≥6 years, with >2 weeks of continuous glucose monitoring (CGM) data pre- and >12 months post-Control-IQ technology initiation were included in the analysis. Results: In total 9451 users met the inclusion criteria, 83% had type 1 diabetes, and the rest had type 2 or other forms of diabetes. The mean age was 42.6 ± 20.8 years, and 52% were female. Median percent time in automation was 94.2% [interquartile range, IQR: 90.1%-96.4%] for the entire 12-month duration of observation, with no significant changes over time. Of these users, 9010 (96.8%) had ≥75% of their CGM data available, that is, sufficient data for reliable computation of CGM-based glycemic outcomes. At baseline, median percent time in range (70-180 mg/dL) was 63.6 (IQR: 49.9%-75.6%) and increased to 73.6% (IQR: 64.4%-81.8%) for the 12 months of Control-IQ technology use with no significant changes over time. Median percent time <70 mg/dL remained consistent at ∼1% (IQR: 0.5%-1.9%). Conclusion: In this real-world use analysis, Control-IQ technology retained, and to some extent exceeded, the results obtained in randomized controlled trials, showing glycemic improvements in a broad age range of people with different types of diabetes.

The Digital/Virtual Diabetes Clinic: The Future Is Now-Recommendations from an International Panel on Diabetes Digital Technologies Introduction.

The increasing prevalence of diabetes, combined with a growing global shortage of health care professionals (HCP), necessitates the need to develop new approaches to diabetes care delivery to expand access to care, lessen the burden on people with diabetes, improve efficiencies, and reduce the unsustainable financial liability on health systems and payers. Use of digital diabetes technologies and telehealth protocols within a digital/virtual diabetes clinic has the potential to address these challenges. However, several issues must be resolved to move forward. In February 2020, organizers of the Advanced Technologies & Treatments for Diabetes Annual Conference convened an international panel of HCP, researchers, patient advocates, and industry representatives to review the status of digital diabetes technologies, characterize deficits in current technologies, and identify issues for consideration. Since that meeting, the importance of using telehealth and digital diabetes technologies has been demonstrated amid the global coronavirus disease (COVID-19) pandemic. This article summarizes the panel's discussion of the opportunities, obstacles, and requisites for advancing the use of these technologies as a standard of care for the management of diabetes.

Evening and overnight closed-loop control versus 24/7 continuous closed-loop control for type 1 diabetes: a randomised crossover trial.

Background: Automated closed-loop control (CLC), known as the "artificial pancreas" is emerging as a treatment option for Type 1 Diabetes (T1D), generally superior to sensor-augmented insulin pump (SAP) treatment. It is postulated that evening-night (E-N) CLC may account for most of the benefits of 24-7 CLC; however, a direct comparison has not been done. Methods: In this trial (NCT02679287), adults with T1D were randomised 1:1 to two groups, which followed different sequences of four 8-week sessions, resulting in two crossover designs comparing SAP vs E-N CLC and E-N CLC vs 24-7 CLC, respectively. Eligibility: T1D for at least 1 year, using an insulin pump for at least six months, ages 18 years or older. Primary hypothesis: E-N CLC compared to SAP will decrease percent time <70mg/dL (3.9mmol/L) measured by continuous glucose monitoring (CGM) without deterioration in HbA1c. Secondary Hypotheses: 24-7 CLC compared to SAP will increase CGM-measured time in target range (TIR, 70-180mg/dL; 3.9-10mmol/L) and will reduce glucose variability during the day. Findings: Ninety-three participants were randomised and 80 were included in the analysis, ages 18-69 years; HbA1c levels 5.4-10.6%; 66% female. Compared to SAP, E-N CLC reduced overall time <70mg/dL from 4.0% to 2.2% () resulting in an absolute difference of 1.8% (95%CI: 1.2-2.4%), p<0.0001. This was accompanied by overall reduction in HbA1c from 7.4% at baseline to 7.1% at the end of study, resulting in an absolute difference of 0.3% (95% CI: 0.1-0.4%), p<0.0001. There were 5 severe hypoglycaemia adverse events attributed to user-directed boluses without malfunction of the investigational device, and no diabetic ketoacidosis events. Interpretation: In type 1 diabetes, evening-night closed-loop control was superior to sensor-augmented pump therapy, achieving most of the glycaemic benefits of 24-7 closed-loop.

Glycemic Outcomes of Use of CLC Versus PLGS in Type 1 Diabetes: A Randomized Controlled Trial.

OBJECTIVE: Limited information is available about glycemic outcomes with a closed-loop control (CLC) system compared with a predictive low-glucose suspend (PLGS) system. RESEARCH DESIGN AND METHODS: After 6 months of use of a CLC system in a randomized trial, 109 participants with type 1 diabetes (age range, 14-72 years; mean HbA1c, 7.1% [54 mmol/mol]) were randomly assigned to CLC (N = 54, Control-IQ) or PLGS (N = 55, Basal-IQ) groups for 3 months. The primary outcome was continuous glucose monitor (CGM)-measured time in range (TIR) for 70-180 mg/dL. Baseline CGM metrics were computed from the last 3 months of the preceding study. RESULTS: All 109 participants completed the study. Mean ± SD TIR was 71.1 ± 11.2% at baseline and 67.6 ± 12.6% using intention-to-treat analysis (69.1 ± 12.2% using per-protocol analysis excluding periods of study-wide suspension of device use) over 13 weeks on CLC vs. 70.0 ± 13.6% and 60.4 ± 17.1% on PLGS (difference = 5.9%; 95% CI 3.6%, 8.3%; P < 0.001). Time >180 mg/dL was lower in the CLC group than PLGS group (difference = -6.0%; 95% CI -8.4%, -3.7%; P < 0.001) while time <54 mg/dL was similar (0.04%; 95% CI -0.05%, 0.13%; P = 0.41). HbA1c after 13 weeks was lower on CLC than PLGS (7.2% [55 mmol/mol] vs. 7.5% [56 mmol/mol], difference -0.34% [-3.7 mmol/mol]; 95% CI -0.57% [-6.2 mmol/mol], -0.11% [1.2 mmol/mol]; P = 0.0035). CONCLUSIONS: Following 6 months of CLC, switching to PLGS reduced TIR and increased HbA1c toward their pre-CLC values, while hypoglycemia remained similarly reduced with both CLC and PLGS.

A Review of Continuous Glucose Monitoring-Based Composite Metrics for Glycemic Control.

We performed a literature review of composite metrics for describing the quality of glycemic control, as measured by continuous glucose monitors (CGMs). Nine composite metrics that describe CGM data were identified. They are described in detail along with their advantages and disadvantages. The primary benefit to using composite metrics in clinical practice is to be able to quickly evaluate a patient's glycemic control in the form of a single number that accounts for multiple dimensions of glycemic control. Very little data exist about (1) how to select the optimal components of composite metrics for CGM; (2) how to best score individual components of composite metrics; and (3) how to correlate composite metric scores with empiric outcomes. Nevertheless, composite metrics are an attractive type of scoring system to present clinicians with a single number that accounts for many dimensions of their patients' glycemia. If a busy health care professional is looking for a single-number summary statistic to describe glucose levels monitored by a CGM, then a composite metric has many attractive features.

Six-Month Randomized, Multicenter Trial of Closed-Loop Control in Type 1 Diabetes.

BACKGROUND: Closed-loop systems that automate insulin delivery may improve glycemic outcomes in patients with type 1 diabetes. METHODS: In this 6-month randomized, multicenter trial, patients with type 1 diabetes were assigned in a 2:1 ratio to receive treatment with a closed-loop system (closed-loop group) or a sensor-augmented pump (control group). The primary outcome was the percentage of time that the blood glucose level was within the target range of 70 to 180 mg per deciliter (3.9 to 10.0 mmol per liter), as measured by continuous glucose monitoring. RESULTS: A total of 168 patients underwent randomization; 112 were assigned to the closed-loop group, and 56 were assigned to the control group. The age range of the patients was 14 to 71 years, and the glycated hemoglobin level ranged from 5.4 to 10.6%. All 168 patients completed the trial. The mean (±SD) percentage of time that the glucose level was within the target range increased in the closed-loop group from 61±17% at baseline to 71±12% during the 6 months and remained unchanged at 59±14% in the control group (mean adjusted difference, 11 percentage points; 95% confidence interval [CI], 9 to 14; P<0.001). The results with regard to the main secondary outcomes (percentage of time that the glucose level was >180 mg per deciliter, mean glucose level, glycated hemoglobin level, and percentage of time that the glucose level was <70 mg per deciliter or <54 mg per deciliter [3.0 mmol per liter]) all met the prespecified hierarchical criterion for significance, favoring the closed-loop system. The mean difference (closed loop minus control) in the percentage of time that the blood glucose level was lower than 70 mg per deciliter was -0.88 percentage points (95% CI, -1.19 to -0.57; P<0.001). The mean adjusted difference in glycated hemoglobin level after 6 months was -0.33 percentage points (95% CI, -0.53 to -0.13; P = 0.001). In the closed-loop group, the median percentage of time that the system was in closed-loop mode was 90% over 6 months. No serious hypoglycemic events occurred in either group; one episode of diabetic ketoacidosis occurred in the closed-loop group. CONCLUSIONS: In this 6-month trial involving patients with type 1 diabetes, the use of a closed-loop system was associated with a greater percentage of time spent in a target glycemic range than the use of a sensor-augmented insulin pump. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases; iDCL ClinicalTrials.gov number, NCT03563313.).

Hybrid Closed-Loop Control Is Safe and Effective for People with Type 1 Diabetes Who Are at Moderate to High Risk for Hypoglycemia.

Background: Typically, closed-loop control (CLC) studies excluded patients with significant hypoglycemia. We evaluated the effectiveness of hybrid CLC (HCLC) versus sensor-augmented pump (SAP) in reducing hypoglycemia in this high-risk population. Methods: Forty-four subjects with type 1 diabetes, 25 women, 37 ± 2 years old, HbA1c 7.4% ± 0.2% (57 ± 1.5 mmol/mol), diabetes duration 19 ± 2 years, on insulin pump, were enrolled at the University of Virginia (N = 33) and Stanford University (N = 11). Eligibility: increased risk of hypoglycemia confirmed by 1 week of blinded continuous glucose monitor (CGM); randomized to 4 weeks of home use of either HCLC or SAP. Primary/secondary outcomes: risk for hypoglycemia measured by the low blood glucose index (LBGI)/CGM-based time in ranges. Results: Values reported: mean ± standard deviation. From baseline to the final week of study: LBGI decreased more on HCLC (2.51 ± 1.17 to 1.28 ± 0.5) than on SAP (2.1 ± 1.05 to 1.79 ± 0.98), P < 0.001; percent time below 70 mg/dL (3.9 mmol/L) decreased on HCLC (7.2% ± 5.3% to 2.0% ± 1.4%) but not on SAP (5.8% ± 4.7% to 4.8% ± 4.5%), P = 0.001; percent time within the target range 70-180 mg/dL (3.9-10 mmol/L) increased on HCLC (67.8% ± 13.5% to 78.2% ± 10%) but decreased on SAP (65.6% ± 12.9% to 59.6% ± 16.5%), P < 0.001; percent time above 180 mg/dL (10 mmol/L) decreased on HCLC (25.1% ± 15.3% to 19.8% ± 10.1%) but increased on SAP (28.6% ± 14.6% to 35.6% ± 17.6%), P = 0.009. Mean glucose did not change significantly on HCLC (144.9 ± 27.9 to 143.8 ± 14.4 mg/dL [8.1 ± 1.6 to 8.0 ± 0.8 mmol/L]) or SAP (152.5 ± 24.3 to 162.4 ± 28.2 [8.5 ± 1.4 to 9.0 ± 1.6]), P = ns. Conclusions: Compared with SAP therapy, HCLC reduced the risk and frequency of hypoglycemia, while improving time in target range and reducing hyperglycemia in people at moderate to high risk of hypoglycemia.

Closed loop control in adolescents and children during winter sports: Use of the Tandem Control-IQ AP system.

OBJECTIVE: Artificial pancreas (AP) systems have been shown to improve glycemic control throughout the day and night in adults, adolescents, and children. However, AP testing remains limited during intense and prolonged exercise in adolescents and children. We present the performance of the Tandem Control-IQ AP system in adolescents and children during a winter ski camp study, where high altitude, low temperature, prolonged intense activity, and stress challenged glycemic control. METHODS: In a randomized controlled trial, 24 adolescents (ages 13-18 years) and 24 school-aged children (6-12 years) with Type 1 diabetes (T1D) participated in a 48 hours ski camp (∼5 hours skiing/day) at three sites: Wintergreen, VA; Kirkwood, and Breckenridge, CO. Study participants were randomized 1:1 at each site. The control group used remote monitored sensor-augmented pump (RM-SAP), and the experimental group used the t: slim X2 with Control-IQ Technology AP system. All subjects were remotely monitored 24 hours per day by study staff. RESULTS: The Control-IQ system improved percent time within range (70-180 mg/dL) over the entire camp duration: 66.4 ± 16.4 vs 53.9 ± 24.8%; P = .01 in both children and adolescents. The AP system was associated with a significantly lower average glucose based on continuous glucose monitor data: 161 ± 29.9 vs 176.8 ± 36.5 mg/dL; P = .023. There were no differences between groups for hypoglycemia exposure or carbohydrate interventions. There were no adverse events. CONCLUSIONS: The use of the Control-IQ AP improved glycemic control and safely reduced exposure to hyperglycemia relative to RM-SAP in pediatric patients with T1D during prolonged intensive winter sport activities.

The International Diabetes Closed-Loop Study: Testing Artificial Pancreas Component Interoperability.

BACKGROUND: Use of artificial pancreas (AP) requires seamless interaction of device components, such as continuous glucose monitor (CGM), insulin pump, and control algorithm. Mobile AP configurations also include a smartphone as computational hub and gateway to cloud applications (e.g., remote monitoring and data review and analysis). This International Diabetes Closed-Loop study was designed to demonstrate and evaluate the operation of the inControl AP using different CGMs and pump modalities without changes to the user interface, user experience, and underlying controller. METHODS: Forty-three patients with type 1 diabetes (T1D) were enrolled at 10 clinical centers (7 United States, 3 Europe) and 41 were included in the analyses (39% female, >95% non-Hispanic white, median T1D duration 16 years, median HbA1c 7.4%). Two CGMs and two insulin pumps were tested by different study participants/sites using the same system hub (a smartphone) during 2 weeks of in-home use. RESULTS: The major difference between the system components was the stability of their wireless connections with the smartphone. The two sensors achieved similar rates of connectivity as measured by percentage time in closed loop (75% and 75%); however, the two pumps had markedly different closed-loop adherence (66% vs. 87%). When connected, all system configurations achieved similar glycemic outcomes on AP control (73% [mean] time in range: 70-180 mg/dL, and 1.7% [median] time <70 mg/dL). CONCLUSIONS: CGMs and insulin pumps can be interchangeable in the same Mobile AP system, as long as these devices achieve certain levels of reliability and wireless connection stability.

Continuous Glucose Monitoring and Insulin Informed Advisory System with Automated Titration and Dosing of Insulin Reduces Glucose Variability in Type 1 Diabetes Mellitus.

BACKGROUND: Glucose variability (GV) remains a key limiting factor in the success of diabetes management. While new technologies, for example, accurate continuous glucose monitoring (CGM) and connected insulin delivery devices, are now available, current treatment standards fail to leverage the wealth of information generated. Expert systems, from automated insulin delivery to advisory systems, are a key missing element to richer, more personalized, glucose management in diabetes. METHODS: Twenty four subjects with type 1 diabetes mellitus (T1DM), 15 women, 37 ± 11 years of age, hemoglobin A1c 7.2% ± 1%, total daily insulin (TDI) 46.7 ± 22.3 U, using either an insulin pump or multiple daily injections with carbohydrate counting, completed two randomized crossover 48-h visits at the University of Virginia, wearing Dexcom G4 CGM, and using either usual care or the UVA decision support system (DSS). DSS consisted of a combination of automated insulin titration, bolus calculation, and CHO treatment advice. During each admission, participants were exposed to a variety of meal sizes and contents and two 45-min bouts of exercise. GV and glucose control were assessed using CGM. RESULTS: The use of DSS significantly reduced GV (coefficient of variation: 0.36 ± 08. vs. 0.33 ± 0.06, P = 0.045) while maintaining glycemic control (average CGM: 155.2 ± 27.1 mg/dL vs. 155.2 ± 23.2 mg/dL), by reducing hypoglycemia exposure (%<70 mg/dL: 3.8% ± 4.6% vs. 1.8% ± 2%, P = 0.018), with nonsignificant trends toward reduction of significant hyperglycemia overnight (%>250 mg/dL: 5.3% ± 9.5% vs. 1.9% ± 4.6%) and at mealtime (11.3% ± 14.8% vs. 5.8% ± 9.1%). CONCLUSIONS: A CGM/insulin informed advisory system proved to be safe and feasible in a cohort of 24 T1DM subjects. Use of the system may result in reduced GV and improved protection against hypoglycemia.