Closed-loop systems that automate insulin delivery may improve glycemic outcomes in patients with type 1 diabetes.
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.
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.
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.).
Parental sleep quality may contribute to glycemic control in youth with type 1 diabetes. In this article we present sleep analysis from a multicenter, randomized trial of children ages 6-13 years ...with type 1 diabetes evaluating the Tandem Control-IQ (CIQ) hybrid closed-loop (HCL) system.
Pittsburgh Sleep Quality Index (PSQI) scores were assessed at baseline to identify parents as "poor" sleepers (PSQI >5). Glycemic and psycho-behavioral outcomes before and after CIQ use were analyzed in poor sleepers (n = 49) and their children.
Nocturnal time in range (P < 0.001) and time hyperglycemic (P < 0.001), Hypoglycemia Fear Survey for Parents score (P < 0.001), Problem Areas in Diabetes scale score (P < 0.001), PSQI score (P < 0.001), and Hypoglycemia Fear Survey for Children score (P = 0.025) significantly improved. Of poor sleepers, 27 became good sleepers (PSQI score <5).
Use of CIQ in youth with type 1 diabetes ages 6-13 years significantly improved sleep and psychosocial measures in parent poor sleepers, coinciding with improvements in child nocturnal glycemia, highlighting the relationship between HCL systems and parent sleep quality.
This study evaluated a new insulin delivery system designed to reduce insulin delivery when trends in continuous glucose monitoring (CGM) glucose concentrations predict future hypoglycemia.
...Individuals with type 1 diabetes (
= 103, age 6-72 years, mean HbA
7.3% 56 mmol/mol) participated in a 6-week randomized crossover trial to evaluate the efficacy and safety of a Tandem Diabetes Care t:slim X2 pump with Basal-IQ integrated with a Dexcom G5 sensor and a predictive low-glucose suspend algorithm (PLGS) compared with sensor-augmented pump (SAP) therapy. The primary outcome was CGM-measured time <70 mg/dL.
Both study periods were completed by 99% of participants; median CGM usage exceeded 90% in both arms. Median time <70 mg/dL was reduced from 3.6% at baseline to 2.6% during the 3-week period in the PLGS arm compared with 3.2% in the SAP arm (difference PLGS - SAP = -0.8%, 95% CI -1.1 to -0.5,
< 0.001). The corresponding mean values were 4.4%, 3.1%, and 4.5%, respectively, represent-ing a 31% reduction in the time <70 mg/dL with PLGS. There was no increase in mean glucose concentration (159 vs. 159 mg/dL,
= 0.40) or percentage of time spent >180 mg/dL (32% vs. 33%,
= 0.12). One severe hypoglycemic event occurred in the SAP arm and none in the PLGS arm. Mean pump suspension time was 104 min/day.
The Tandem Diabetes Care Basal-IQ PLGS system significantly reduced hypoglycemia without rebound hyperglycemia, indicating that the system can benefit adults and youth with type 1 diabetes in improving glycemic control.
Overnight hypoglycemia occurs frequently in individuals with type 1 diabetes and can result in loss of consciousness, seizure, or even death. We conducted an in-home randomized trial to determine ...whether nocturnal hypoglycemia could be safely reduced by temporarily suspending pump insulin delivery when hypoglycemia was predicted by an algorithm based on continuous glucose monitoring (CGM) glucose levels.
Following an initial run-in phase, a 42-night trial was conducted in 45 individuals aged 15-45 years with type 1 diabetes in which each night was assigned randomly to either having the predictive low-glucose suspend system active (intervention night) or inactive (control night). The primary outcome was the proportion of nights in which ≥1 CGM glucose values ≤60 mg/dL occurred.
Overnight hypoglycemia with at least one CGM value ≤60 mg/dL occurred on 196 of 942 (21%) intervention nights versus 322 of 970 (33%) control nights (odds ratio 0.52 95% CI 0.43-0.64; P < 0.001). Median hypoglycemia area under the curve was reduced by 81%, and hypoglycemia lasting >2 h was reduced by 74%. Overnight sensor glucose was >180 mg/dL during 57% of control nights and 59% of intervention nights (P = 0.17), while morning blood glucose was >180 mg/dL following 21% and 27% of nights, respectively (P < 0.001), and >250 mg/dL following 6% and 6%, respectively. Morning ketosis was present <1% of the time in each arm.
Use of a nocturnal low-glucose suspend system can substantially reduce overnight hypoglycemia without an increase in morning ketosis.
This study assessed the accuracy of a factory-calibrated 10-day real-time continuous glucose monitoring (CGM) system (G6), which includes an automated sensor applicator.
Seventy-six participants with ...insulin-treated diabetes were enrolled at four U.S. sites as part of a larger study of G6 system performance. In-clinic visits for frequent comparative blood glucose measurements using a reference instrument (YSI) were conducted on days 1, 4-5, 7, and/or 10 of system use. Accuracy evaluation included the proportion of CGM values that were within ±20% of YSI reference value for glucose levels >100 mg/dL and ±20 mg/dL for YSI glucose levels ≤100 mg/dL (%20/20), the analogous %15/15 and %30/30, and the mean absolute relative difference (MARD) between temporally matched CGM and YSI values. Participants calibrated the systems once daily. Raw sensor data were reprocessed using assigned sensor codes and a factory-calibration algorithm.
Reprocessed data from 62 participants (25 adults and 37 children and adolescents of ages 6-17 years; 3532 YSI-CGM pairs) were analyzed. The G6 system's overall %20/20 was 93.9% (adults, 92.5%; children and adolescents, 96.2%), its %15/15 was 83.3% (adults, 78.3%; children and adolescents, 91.1%), and its MARD was 9.0% (adults, 9.8%; children and adolescents, 7.7%). Overall day-1 %20/20 accuracy was 92.2%, %15/15 was 81.5%, and MARD was 9.3%. Accuracy was maintained across 10 days of use and various glucose concentration ranges in both adults and children and adolescents.
The G6 system utilizing an automated sensor applicator provides accurate glucose readings in adults and children and adolescents throughout the 10-day sensor life.
Frequent use of continuous glucose monitoring (CGM) systems is associated with improved glycemic outcomes in persons with diabetes, but the need for calibrations and sensor insertions are often ...barriers to adoption. In this study, we evaluated the performance of G6, a sixth-generation, factory-calibrated CGM system specified for 10-day wear.
The study enrolled participants of ages 6 years and up with type 1 diabetes or insulin-treated type 2 diabetes at 11 sites in the United States. Participation involved one sensor wear period of up to 10 days. Adults wore the system on the abdomen; youth of ages 6-17 years could choose to wear it on the abdomen or upper buttocks. Clinic sessions for frequent comparison with reference blood glucose measurements took place on days 1, 4-5, 7, and/or 10. Participants of ages 13 years and up underwent purposeful supervised glucose manipulation during in-clinic sessions. During the study, participants calibrated the systems once daily. However, analysis was performed on glucose values that were derived from reprocessed raw sensor data, independently of self-monitored blood glucose values used for calibration. Reprocessing used assigned sensor codes and a factory-calibration algorithm. Performance evaluation included the proportion of CGM values that were within ±20% of reference glucose values >100 mg/dL or within ±20 mg/dL of reference glucose values ≤100 mg/dL (%20/20), the analogous %15/15, and the mean absolute relative difference (MARD, expressed as a percentage) between temporally matched CGM and reference values.
Data from 262 study participants (21,569 matched CGM reference pairs) were analyzed. The overall %15/15, %20/20, and MARD were 82.4%, 92.3%, and 10.0%, respectively. Matched pairs from 134 adults and 128 youth of ages 6-17 years were similar with respect to %20/20 (92.4% and 91.9%) and MARD (9.9% and 10.1%). Overall %20/20 values on days 1 and 10 of sensor wear were 88.6% and 90.6%, respectively. The system's "Urgent Low Soon" (predictive of hypoglycemia within 20 min) hypoglycemia alert was correctly provided 84% of the time within 30 min before impending biochemical hypoglycemia (<70 mg/dL). The 10-day sensor survival rate was 87%.
The new factory-calibrated G6 real-time CGM system provides accurate readings for 10 days and removes several clinical barriers to broader CGM adoption.
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.
To evaluate if presence of cardiovascular (CV) risk factors and their clustering as metabolic syndrome (MetS) is associated with increased arterial stiffness and accelerated progression over time ...among youth with type 1 diabetes.
Longitudinal study of 298 youth with type 1 diabetes (age 14.5 years; 46.3% female; duration 4.8 years), with two research visits conducted 5 years apart. CV factors included: waist circumference, blood pressure (BP), fasting lipids (HDL cholesterol, LDL cholesterol LDL-c, triglycerides), albumin/creatinine ratio, and HbA1c. MetS was based on Adult Treatment Panel III criteria modified for youth. Pulse wave velocity (PWV) in the carotid-femoral segment was measured by tonometry. Mixed models were used to assess the rate of progression in PWV and the association between CV factors and PWV over time.
PWV increased significantly over time (0.145 m/s/year; P < 0.0001). MetS (P = 0.0035), large waist (P < 0.0001), and elevated BP (P = 0.0003) at baseline were each associated with worse PWV over time. These baseline factors, however, did not significantly influence the rate of progression. Increases in waist circumference (P < 0.0001), LDL-c levels (P = 0.0156), and declining glucose control (HbA1c; P = 0.0419) were independently associated with higher PWV over time.
Presence, clustering, and worsening of CV risk factors are associated with increased arterial stiffness over time in youth with type 1 diabetes. Whether improvement in CV risk factors early in life will slow the progression of arterial stiffness and reduce the burden of CV disease in this population requires further study.
Adolescents and young adults with type 1 diabetes exhibit the worst glycemic control among individuals with type 1 diabetes across the lifespan. Although continuous glucose monitoring (CGM) has been ...shown to improve glycemic control in adults, its benefit in adolescents and young adults has not been demonstrated.
To determine the effect of CGM on glycemic control in adolescents and young adults with type 1 diabetes.
Randomized clinical trial conducted between January 2018 and May 2019 at 14 endocrinology practices in the US including 153 individuals aged 14 to 24 years with type 1 diabetes and screening hemoglobin A1c (HbA1c) of 7.5% to 10.9%.
Participants were randomized 1:1 to undergo CGM (CGM group; n = 74) or usual care using a blood glucose meter for glucose monitoring (blood glucose monitoring BGM group; n = 79).
The primary outcome was change in HbA1c from baseline to 26 weeks. There were 20 secondary outcomes, including additional HbA1c outcomes, CGM glucose metrics, and patient-reported outcomes with adjustment for multiple comparisons to control for the false discovery rate.
Among the 153 participants (mean SD age, 17 3 years; 76 50% were female; mean SD diabetes duration, 9 5 years), 142 (93%) completed the study. In the CGM group, 68% of participants used CGM at least 5 days per week in month 6. Mean HbA1c was 8.9% at baseline and 8.5% at 26 weeks in the CGM group and 8.9% at both baseline and 26 weeks in the BGM group (adjusted between-group difference, -0.37% 95% CI, -0.66% to -0.08%; P = .01). Of 20 prespecified secondary outcomes, there were statistically significant differences in 3 of 7 binary HbA1c outcomes, 8 of 9 CGM metrics, and 1 of 4 patient-reported outcomes. The most commonly reported adverse events in the CGM and BGM groups were severe hypoglycemia (3 participants with an event in the CGM group and 2 in the BGM group), hyperglycemia/ketosis (1 participant with an event in CGM group and 4 in the BGM group), and diabetic ketoacidosis (3 participants with an event in the CGM group and 1 in the BGM group).
Among adolescents and young adults with type 1 diabetes, continuous glucose monitoring compared with standard blood glucose monitoring resulted in a small but statistically significant improvement in glycemic control over 26 weeks. Further research is needed to understand the clinical importance of the findings.
ClinicalTrials.gov Identifier: NCT03263494.
To describe predictors of hybrid closed loop (HCL) discontinuation and perceived barriers to use in youth with type 1 diabetes.
Youth with type 1 diabetes (eligible age 2-25 y; recruited age 8-25 y) ...who initiated the Minimed 670G HCL system were followed prospectively for 6 mo in an observational study.
Demographic, glycemic (time-in-range, HbA1c), and psychosocial variables Hypoglycemia Fear Survey (HFS); Problem Areas in Diabetes (PAID) were collected for all participants. Participants who discontinued HCL (<10% HCL use at clinical visit) completed a questionnaire on perceived barriers to HCL use.
Ninety-two youth (15.7 ± 3.6 y, HbA1c 8.8 ± 1.3%, 50% female) initiated HCL, and 28 (30%) discontinued HCL, with the majority (64%) discontinuing between 3 and 6 mo after HCL start. Baseline HbA1c predicted discontinuation (P = .026) with the odds of discontinuing 2.7 times higher (95% CI: 1.123, 6.283) for each 1% increase in baseline HbA1c. Youth who discontinued HCL rated difficulty with calibrations, number of alarms, and too much time needed to make the system work as the most problematic aspects of HCL. Qualitatively derived themes included technological difficulties (error alerts, not working correctly), too much work (calibrations, fingersticks), alarms, disappointment in glycemic control, and expense (cited by parents).
Youth with higher HbA1c are at greater risk for discontinuing HCL than youth with lower HbA1c, and should be the target of new interventions to support device use. The primary reasons for discontinuing HCL relate to the workload required to use HCL.
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