OBJECTIVE
To identify and define clinically meaningful type 1 diabetes outcomes beyond hemoglobin A1c (HbA1c) based upon a review of the evidence, consensus from clinical experts, and input from ...researchers, people with type 1 diabetes, and industry. Priority outcomes include hypoglycemia, hyperglycemia, time in range, diabetic ketoacidosis (DKA), and patient-reported outcomes (PROs). While priority outcomes for type 1 and type 2 diabetes may overlap, type 1 diabetes was the focus of this work.
RESEARCH AND METHODS
A Steering Committee—comprising representatives from the American Association of Clinical Endocrinologists, the American Association of Diabetes Educators, the American Diabetes Association, the Endocrine Society, JDRF International, The Leona M. and Harry B. Helmsley Charitable Trust, the Pediatric Endocrine Society, and the T1D Exchange—was the decision-making body for the Type 1 Diabetes Outcomes Program. Their work was informed by input from researchers, industry, and people with diabetes through Advisory Committees representing each stakeholder group. Stakeholder surveys were used to identify priority outcomes. The outcomes prioritized in the surveys were hypoglycemia, hyperglycemia, time in range, DKA, and PROs. To develop consensus on the definitions of these outcomes, the Steering Committee relied on published evidence, their clinical expertise, and feedback from the Advisory Committees.
RESULTS
The Steering Committee developed definitions for hypoglycemia, hyperglycemia, time in range, and DKA in type 1 diabetes. The definitions reflect their assessment of the outcome’s short- and long-term clinical impact on people with type 1 diabetes. Knowledge gaps to be addressed by future research were identified. The Steering Committee discussed PROs and concluded that further type 1 diabetes–specific development is needed.
CONCLUSIONS
The Steering Committee recommends use of the defined clinically meaningful outcomes beyond HbA1c in the research, development, and evaluation of type 1 diabetes therapies.
A closed-loop system (also called an artificial pancreas) may improve glycemic outcomes in children with type 1 diabetes. In this 16-week trial, the glucose level was in the target range for a ...greater percentage of time with a closed-loop system than with a sensor-augmented insulin pump.
The American Diabetes Association published the position statement for the care of children and adoloscents with type 1 diabetes. Innovations have transformed the landscape and management of type 1 ...diabetes. However, strategies to prevent or delay type 1 diabetes in youth remain elusive and meanwhile the number of affected children continues to grow.
The MiniMed 670G System is the first commercial hybrid closed-loop (HCL) system for management of type 1 diabetes. Using data from adolescent and young adult participants, we compared insulin ...delivery patterns and time-in-range metrics in HCL (Auto Mode) and open loop (OL). System alerts, usage profiles, and operational parameters were examined to provide suggestions for optimal clinical use of the system.
Data from 31 adolescent and young adult participants (14-26 years old) at three clinical sites in the 670G pivotal trial were analyzed. Participants had a 2-week run-in period in OL, followed by a 3-month in-home study phase with HCL functionality enabled. Data were compared between baseline OL and HCL use after 1 week, 1 month, 2 months, and 3 months.
Carbohydrate-to-insulin (C-to-I) ratios were more aggressive for all meals with HCL compared with baseline OL. Total daily insulin dose and basal-to-bolus ratio did not change during the trial. Time in range increased 14% with use of Auto Mode after 3 months (
< 0.001), and HbA
decreased 0.75%. Auto Mode exits were primarily due to sensor/insulin delivery alerts and hyperglycemia. The percentage of time in Auto Mode gradually declined from 87%, with a final use rate of 72% (-15%).
In transitioning young patients to the 670G system, providers should anticipate immediate C-to-I ratio adjustments while also assessing active insulin time. Users should anticipate occasional Auto Mode exits, which can be reduced by following system instructions and reliably bolusing for meals. Unique 670G system functionality requires ongoing clinical guidance and education from providers.
Management of type 1 diabetes is challenging. We compared outcomes using a commercially available hybrid closed-loop system versus a new investigational system with features potentially useful for ...adolescents and young adults with type 1 diabetes.
In this multinational, randomised, crossover trial (Fuzzy Logic Automated Insulin Regulation FLAIR), individuals aged 14–29 years old, with a clinical diagnosis of type 1 diabetes with a duration of at least 1 year, using either an insulin pump or multiple daily insulin injections, and glycated haemoglobin (HbA1c) levels of 7·0–11·0% (53–97 mmol/mol) were recruited from seven academic-based endocrinology practices, four in the USA, and one each in Germany, Israel, and Slovenia. After a run-in period to teach participants how to use the study pump and continuous glucose monitor, participants were randomly assigned (1:1) using a computer-generated sequence, with a permuted block design (block sizes of two and four), stratified by baseline HbA1c and use of a personal MiniMed 670G system (Medtronic) at enrolment, to either use of a MiniMed 670G hybrid closed-loop system (670G) or the investigational advanced hybrid closed-loop system (Medtronic) for the first 12-week period, and then participants were crossed over with no washout period, to the other group for use for another 12 weeks. Masking was not possible due to the nature of the systems used. The coprimary outcomes, measured with continuous glucose monitoring, were proportion of time that glucose levels were above 180 mg/dL (>10·0 mmol/L) during 0600 h to 2359 h (ie, daytime), tested for superiority, and proportion of time that glucose levels were below 54 mg/dL (<3·0 mmol/L) calculated over a full 24-h period, tested for non-inferiority (non-inferiority margin 2%). Analysis was by intention to treat. Safety was assessed in all participants randomly assigned to treatment. This trial is registered with ClinicalTrials.gov, NCT03040414, and is now complete.
Between June 3 and Aug 22, 2019, 113 individuals were enrolled into the trial. Mean age was 19 years (SD 4) and 70 (62%) of 113 participants were female. Mean proportion of time with daytime glucose levels above 180 mg/dL (>10·0 mmol/L) was 42% (SD 13) at baseline, 37% (9) during use of the 670G system, and 34% (9) during use of the advanced hybrid closed-loop system (mean difference advanced hybrid closed-loop system minus 670G system −3·00% 95% CI −3·97 to −2·04; p<0·0001). Mean 24-h proportion of time with glucose levels below 54 mg/dL (<3·0 mmol/L) was 0·46% (SD 0·42) at baseline, 0·50% (0·35) during use of the 670G system, and 0·46% (0·33) during use of the advanced hybrid closed-loop system (mean difference advanced hybrid closed-loop system minus 670G system −0·06% 95% CI −0·11 to −0·02; p<0·0001 for non-inferiority). One severe hypoglycaemic event occurred in the advanced hybrid closed-loop system group, determined to be unrelated to study treatment, and none occurred in the 670G group.
Hyperglycaemia was reduced without increasing hypoglycaemia in adolescents and young adults with type 1 diabetes using the investigational advanced hybrid closed-loop system compared with the commercially available MiniMed 670G system. Testing an advanced hybrid closed-loop system in populations that are underserved due to socioeconomic factors and testing during pregnancy and in individuals with impaired awareness of hypoglycaemia would advance the effective use of this technology
National Institute of Diabetes and Digestive and Kidney Diseases.
OBJECTIVE:--The most promising β-cell replacement therapy for children with type 1 diabetes is a closed-loop artificial pancreas incorporating continuous glucose sensors and insulin pumps. The ...Medtronic MiniMed external physiological insulin delivery (ePID) system combines an external pump and sensor with a variable insulin infusion rate algorithm designed to emulate the physiological characteristics of the β-cell. However, delays in insulin absorption associated with the subcutaneous route of delivery inevitably lead to large postprandial glucose excursions. RESEARCH DESIGN AND METHODS--We studied the feasibility of the Medtronic ePID system in youth with type 1 diabetes and hypothesized that small manual premeal "priming" boluses would reduce postprandial excursions during closed-loop control. Seventeen adolescents (aged 15.9 ± 1.6 years; A1C 7.1 ± 0.8%) underwent 34 h of closed-loop control; 8 with full closed-loop (FCL) control and 9 with hybrid closed-loop (HCL) control (premeal priming bolus). RESULTS:--Mean glucose levels were 135 ± 45 mg/dl in the HCL group versus 141 ± 55 mg/dl in the FCL group (P = 0.09); daytime glucose levels averaged 149 ± 47 mg/dl in the HCL group versus 159 ± 59 mg/dl in the FCL group (P = 0.03). Peak postprandial glucose levels averaged 194 ± 47 mg/dl in the HCL group versus 226 ± 51 mg/dl in the FCL group (P = 0.04). Nighttime control was similar in both groups (111 ± 27 vs. 112 ± 28 mg/dl). CONCLUSIONS:--Closed-loop glucose control using an external sensor and insulin pump provides a means to achieve near-normal glucose concentrations in youth with type 1 diabetes during the overnight period. The addition of small manual priming bolus doses of insulin, given 15 min before meals, improves postprandial glycemic excursions.
Measurement of glycated hemoglobin (HbA
) has been the traditional method for assessing glycemic control. However, it does not reflect intra- and interday glycemic excursions that may lead to acute ...events (such as hypoglycemia) or postprandial hyperglycemia, which have been linked to both microvascular and macrovascular complications. Continuous glucose monitoring (CGM), either from real-time use (rtCGM) or intermittently viewed (iCGM), addresses many of the limitations inherent in HbA
testing and self-monitoring of blood glucose. Although both provide the means to move beyond the HbA
measurement as the sole marker of glycemic control, standardized metrics for analyzing CGM data are lacking. Moreover, clear criteria for matching people with diabetes to the most appropriate glucose monitoring methodologies, as well as standardized advice about how best to use the new information they provide, have yet to be established. In February 2017, the Advanced Technologies & Treatments for Diabetes (ATTD) Congress convened an international panel of physicians, researchers, and individuals with diabetes who are expert in CGM technologies to address these issues. This article summarizes the ATTD consensus recommendations and represents the current understanding of how CGM results can affect outcomes.
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