Citations

Objective: To assess the efficacy and safety of closed-loop control (CLC) insulin delivery system in adolescents and young adults with type 1 diabetes. Research Design and Methods: Prespecified subanalysis of outcomes in adolescents and young adults aged 14–24 years old with type 1 diabetes in a previously published 6-month multicenter randomized trial. Participants were randomly assigned 2:1 to CLC (Tandem Control-IQ) or sensor augmented pump (SAP, various pumps+Dexcom G6 CGM) and followed for 6 months. Results: Mean age of the 63 participants was 17 years, median type 1 diabetes duration was 7 years, and mean baseline HbA1c was 8.1%. All 63 completed the trial. Time in range (TIR) increased by 13% with CLC versus decreasing by 1% with SAP (adjusted treatment group difference = +13% [+3.1 h/day]; 95% confidence interval [CI] 9–16, P < 0.001), which largely reflected a reduction in time >180 mg/dL (adjusted difference −12% [−2.9 h/day], P < 0.001). Time <70 mg/dL decreased by 1.6% with CLC versus 0.3% with SAP (adjusted difference −0.7% [−10 min/day], 95% CI −1.0% to −0.2%, P = 0.002). CLC use averaged 89% of the time for 6 months. The mean adjusted difference in HbA1c after 6 months was 0.30% in CLC versus SAP (95% CI −0.67 to +0.08, P = 0.13). There was one diabetic ketoacidosis episode in the CLC group. Conclusions: CLC use for 6 months was substantial and associated with improved TIR and reduced hypoglycemia in adolescents and young adults with type 1 diabetes. Thus, CLC has the potential to improve glycemic outcomes in this challenging age group. The clinical trial was registered with ClinicalTrials.gov (NCT03563313).

Background: Data are limited on the need for and benefits of pump setting optimization with automated insulin delivery. We examined clinical management of a closed-loop control (CLC) system and its relationship to glycemic outcomes. Materials and Methods: We analyzed personal parameter adjustments in 168 participants in a 6-month multicenter trial of CLC with Control-IQ versus sensor-augmented pump (SAP) therapy. Preset parameters (BR = basal rates, CF = correction factors, CR = carbohydrate ratios) were optimized at randomization, 2 and 13 weeks, for safety issues, participant concerns, or initiation by participants' usual diabetes care team. Time in range (TIR 70–180 mg/dL) was compared in the week before and after parameter changes. Results: In 607 encounters for parameter changes, there were fewer adjustments for CLC than SAP (3.4 vs. 4.1/participant). Adjustments involved BR (CLC 69%, SAP 80%), CR (CLC 68%, SAP 50%), CF (CLC 44%, SAP 41%), and overnight parameters (CLC 62%, SAP 75%). TIR before and after adjustments was 71.2% and 71.3% for CLC and 61.0% and 62.9% for SAP. The highest baseline HbA 1c CLC subgroup had the largest TIR improvement (51.2% vs. 57.7%). When a CR was made more aggressive in the CLC group, postprandial time >180 mg/dL was 43.1% before the change and 36.0% after the change. The median postprandial time <70 mg/dL before making CR less aggressive was 1.8%, and after the change was 0.7%. Conclusions: No difference in TIR was detected with parameter changes overall, but they may have an effect in higher HbA 1c subgroups or following user-directed boluses, suggesting that changes may matter more in suboptimal control or during discrete periods of the day. Clinical Trials Registration number: NCT03563313.

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 &lt; 0.001). Time &gt;180 mg/dL was lower in the CLC group than PLGS group (difference = −6.0%; 95% CI −8.4%, −3.7%; P &lt; 0.001) while time &lt;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.

OBJECTIVE Assess the efficacy of inControl AP, a mobile closed-loop control (CLC) system. RESEARCH DESIGN AND METHODS This protocol, NCT02985866, is a 3-month parallel-group, multicenter, randomized unblinded trial designed to compare mobile CLC with sensor-augmented pump (SAP) therapy. Eligibility criteria were type 1 diabetes for at least 1 year, use of insulin pumps for at least 6 months, age ≥14 years, and baseline HbA1c &lt;10.5% (91 mmol/mol). The study was designed to assess two coprimary outcomes: superiority of CLC over SAP in continuous glucose monitor (CGM)–measured time below 3.9 mmol/L and noninferiority in CGM-measured time above 10 mmol/L. RESULTS Between November 2017 and May 2018, 127 participants were randomly assigned 1:1 to CLC (n = 65) versus SAP (n = 62); 125 participants completed the study. CGM time below 3.9 mmol/L was 5.0% at baseline and 2.4% during follow-up in the CLC group vs. 4.7% and 4.0%, respectively, in the SAP group (mean difference −1.7% [95% CI −2.4, −1.0]; P &lt; 0.0001 for superiority). CGM time above 10 mmol/L was 40% at baseline and 34% during follow-up in the CLC group vs. 43% and 39%, respectively, in the SAP group (mean difference −3.0% [95% CI −6.1, 0.1]; P &lt; 0.0001 for noninferiority). One severe hypoglycemic event occurred in the CLC group, which was unrelated to the study device. CONCLUSIONS In meeting its coprimary end points, superiority of CLC over SAP in CGM-measured time below 3.9 mmol/L and noninferiority in CGM-measured time above 10 mmol/L, the study has demonstrated that mobile CLC is feasible and could offer certain usability advantages over embedded systems, provided the connectivity between system components is stable.

Summary Objectives To evaluate obesity and overweight in children with congenital adrenal hyperplasia ( CAH ) and associations with glucocorticoids, fludrocortisone and disease control. Adjusting body mass index‐for‐height‐age ( BMI HA ) percentile is proposed to correct misclassification of obese/overweight status in CAH children with advanced bone age and tall‐for‐age stature. Design Longitudinal. Patients One hundred and ninety‐four children with CAH seen from 1970 to 2013: 124 salt wasting ( SW ); 70 simple virilizing ( SV ); 102 females. Measurements Body mass index (BMI) end‐points were overweight (85–94 percentile) and obese (≥95 percentile). Results Approximately 50% of the children had at least one BMI measurement ≥95 percentile and about 70% had at least one ≥85 percentile. Using BMI HA percentiles, obesity incidence decreased slightly in SW children (47–43%) and markedly in SV children (50–33%); however, overweight status was not reduced. Only 6% of SW and 1% of SV children were persistently obese (≥3 clinic visits) when BMI HA was applied, whereas overweight status persisted in 35% of SW and 33% of SV children. Most obesity or overweight when using BMI HA occurred before age 10 and there was no association with hydrocortisone (HC) or fludrocortisone dosing. Adiposity rebound for SW children occurred by 3·3 years and in SV females by age 3·8 years, over a year earlier than the adiposity rebound for healthy children. Conclusion Children with CAH are at higher risk for early onset obesity and overweight with or without using BMI HA but rates of persistent obesity were lower than previously reported. Careful HC dosing during early childhood is needed to prevent increased weight gain and an early adiposity rebound.