Glucose levels measured with continuous glucose monitoring in uncomplicated pregnancies.

INTRODUCTION: To characterize glucose levels during uncomplicated pregnancies, defined as pregnancy with a hemoglobin A1c <5.7% (<39 mmol/mol) in early pregnancy, and without a large-for-gestational-age birth, hypertensive disorders of pregnancy, or gestational diabetes mellitus (ie, abnormal oral glucose tolerance test). RESEARCH DESIGN AND METHODS: Two sites enrolled 937 pregnant individuals aged 18 years and older prior to reaching 17 gestational weeks; 413 had an uncomplicated pregnancy (mean±SD body mass index (BMI) of 25.3±5.0 kg/m2) and wore Dexcom G6 continuous glucose monitoring (CGM) devices throughout the observed gestational period. Mealtimes were voluntarily recorded. Glycemic levels during gestation were characterized using CGM-measured glycemic metrics. RESULTS: Participants wore CGM for a median of 123 days each. Glucose levels were nearly stable throughout all three trimesters in uncomplicated pregnancies. Overall mean±SD glucose during gestation was 98±7 mg/dL (5.4±0.4 mmol/L), median per cent time 63-120 mg/dL (3.5-6.7 mmol/L) was 86% (IQR: 82-89%), median per cent time <63 mg/dL (3.5 mmol/L) was 1.8%, median per cent time >120 mg/dL (6.7 mmol/L) was 11%, and median per cent time >140 mg/dL (7.8 mmol/L) was 2.5%. Mean post-prandial peak glucose was 126±22 mg/dL (7.0±1.2 mmol/L), and mean post-prandial glycemic excursion was 36±22 mg/dL (2.0±1.2 mmol/L). Higher mean glucose levels were low to moderately associated with pregnant individuals with higher BMIs (103±6 mg/dL (5.7±0.3 mmol/L) for BMI ≥30.0 kg/m2 vs 96±7 mg/dL (5.3±0.4 mmol/L) for BMI 18.5-<25 kg/m2, r=0.35). CONCLUSIONS: Mean glucose levels and time 63-120 mg/dL (3.5-6.7 mmol/L) remained nearly stable throughout pregnancy and values above 140 mg/dL (7.8 mmol/L) were rare. Mean glucose levels in pregnancy trend higher as BMI increases into the overweight/obesity range. The glycemic metrics reported during uncomplicated pregnancies represent treatment targets for pregnant individuals.

Continuous Glucose Monitoring Profiles in Pregnancies With and Without Gestational Diabetes Mellitus.

OBJECTIVE: To determine whether continuous glucose monitoring (CGM)-derived glycemic patterns can characterize pregnancies with gestational diabetes mellitus (GDM) as diagnosed by standard oral glucose tolerance test at 24-28 weeks' gestation compared with those without GDM. RESEARCH DESIGN AND METHODS: The analysis includes 768 individuals enrolled from two sites prior to 17 weeks' gestation between June 2020 and December 2021 in a prospective observational study. Participants wore blinded Dexcom G6 CGMs throughout gestation. Main outcome of interest was a diagnosis of GDM by oral glucose tolerance test (OGTT). Glycemic levels in participants with GDM versus without GDM were characterized using CGM-measured glycemic metrics. RESULTS: Participants with GDM (n = 58 [8%]) had higher mean glucose (109 ± 13 vs. 100 ± 8 mg/dL [6.0 ± 0.7 vs. 5.6 ± 0.4 mmol/L], P < 0.001), greater glucose SD (23 ± 4 vs. 19 ± 3 mg/dL [1.3 ± 0.2 vs. 1.1 ± 0.2 mmol/L], P < 0.001), less time in range 63-120 mg/dL (3.5-6.7 mmol/L) (70% ± 17% vs. 84% ± 8%, P < 0.001), greater percent time >120 mg/dL (>6.7 mmol/L) (median 23% vs. 12%, P < 0.001), and greater percent time >140 mg/dL (>7.8 mmol/L) (median 7.4% vs. 2.7%, P < 0.001) than those without GDM throughout gestation prior to OGTT. Median percent time >120 mg/dL (>6.7 mmol/L) and time >140 mg/dL (>7.8 mmol/L) were higher as early as 13-14 weeks of gestation (32% vs. 14%, P < 0.001, and 5.2% vs. 2.0%, P < 0.001, respectively) and persisted during the entire study period prior to OGTT. CONCLUSIONS: Prior to OGTT at 24-34 weeks' gestation, pregnant individuals who develop GDM have higher CGM-measured glucose levels and more hyperglycemia compared with those who do not develop GDM.

Multicenter Evaluation of Ultra-Rapid Lispro (URLi) Insulin with Control-IQ Technology in Adults, Adolescents and Children with Type 1 Diabetes.

OBJECTIVE: To evaluate the safety and explore the efficacy of use of ultra-rapid lispro (URLi, Lyumjev) insulin in the Tandem t:slim X2 insulin pump with Control-IQ 1.5 technology in children, teens and adults living with type 1 diabetes (T1D). METHODS: At 14 U.S. diabetes centers, youth and adults with T1D completed a 16-day lead-in period using lispro in a t:slim X2 insulin pump with Control-IQ 1.5 technology followed by a 13-week period in which URLi insulin was used in the pump. RESULTS: The trial included 179 individuals with type 1 diabetes (T1D) age 6 to 75 years. With URLi, 1.7% (3 participants) had a severe hypoglycemia event over 13 weeks attributed to override boluses or a missed meal. No DKA events occurred. Two participants stopped URLi use due to infusion site discomfort and one stopped after developing a rash. Mean time 70-180 mg/dL (TIR) increased from 65%±15% with lispro to 67%±13% with URLi (P=0.004). Mean insulin treatment satisfaction questionnaire (ITSQ) score improved from 75±13 at screening to 80±11 after 13 weeks of URLi use (mean difference = 6; 95% CI 4 to 8; P<0.001), with the greatest improvement reported for confidence avoiding symptoms of high blood sugar. Mean treatment related impact measure-diabetes (TRIM-D) score improved from 74±12 to 80±12 (P<0.001), and mean TRIM-Diabetes Device (TRIM-DD) score improved from 82±11 to 86±12 (P<0.001). CONCLUSIONS: URLi use in the Tandem t:slim X2 insulin pump with Control-IQ 1.5 technology was safe for adult and pediatric participants with type 1 diabetes, with quality of life benefits of URLi use perceived by the study participants.

Cost-Effectiveness of Closed-Loop Automated Insulin Delivery Using the Cambridge Hybrid Algorithm in Children and Adolescents with Type 1 Diabetes: Results from a Multicenter 6-Month Randomized Trial.

BACKGROUND/OBJECTIVE: The main objective of this study is to evaluate the incremental cost-effectiveness (ICER) of the Cambridge hybrid closed-loop automated insulin delivery (AID) algorithm versus usual care for children and adolescents with type 1 diabetes (T1D). METHODS: This multicenter, binational, parallel-controlled trial randomized 133 insulin pump using participants aged 6 to 18 years to either AID (n = 65) or usual care (n = 68) for 6 months. Both within-trial and lifetime cost-effectiveness were analyzed. Analysis focused on the treatment subgroup (n = 21) who received the much more reliable CamAPS FX hardware iteration and their contemporaneous control group (n = 24). Lifetime complications and costs were simulated via an updated Sheffield T1D policy model. RESULTS: Within-trial, both groups had indistinguishable and statistically unchanged health-related quality of life, and statistically similar hypoglycemia, severe hypoglycemia, and diabetic ketoacidosis (DKA) event rates. Total health care utilization was higher in the treatment group. Both the overall treatment group and CamAPS FX subgroup exhibited improved HbA1C (-0.32%, 95% CI: -0.59 to -0.04; P = .02, and -1.05%, 95% CI: -1.43 to -0.67; P < .001, respectively). Modeling projected increased expected lifespan of 5.36 years and discounted quality-adjusted life years (QALYs) of 1.16 (U.K. tariffs) and 1.52 (U.S. tariffs) in the CamAPS FX subgroup. Estimated ICERs for the subgroup were £19 324/QALY (United Kingdom) and -$3917/QALY (United States). For subgroup patients already using continuous glucose monitors (CGM), ICERs were £10 096/QALY (United Kingdom) and -$33 616/QALY (United States). Probabilistic sensitivity analysis generated mean ICERs of £19 342/QALY (95% CI: £15 903/QALY to £22 929/QALY) (United Kingdom) and -$28 283/QALY (95% CI: -$59 607/QALY to $1858/QALY) (United States). CONCLUSIONS: For children and adolescents with T1D on insulin pump therapy, AID using the Cambridge algorithm appears cost-effective below a £20 000/QALY threshold (United Kingdom) and cost saving (United States).

Impact of impaired awareness of hypoglycemia on glucose decline during and after exercise in T1D: The T1DEXI Study.

OBJECTIVE: To assess whether impaired awareness of hypoglycemia (IAH) affects exercise-associated hypoglycemia in adults with type 1 diabetes (T1D). METHODS: We compared continuous glucose monitoring (CGM)-measured glucose during exercise and for 24-hours following exercise from 95 adults with T1D and IAH (Clarke score ≥4 or ≥1 severe hypoglycemic event within the past year) to 95 'Aware' adults (Clarke score ≤2 and no severe hypoglycemic event within the past year) matched on sex, age, insulin delivery modality, and HbA1c. A total of 4,236 exercise sessions, and 1,794 exercise days and 839 sedentary days, defined as 24-hours following exercise or a day without exercise, respectively, were available for analysis. RESULTS: Participants with IAH exhibited a non-significant trend towards greater decline in glucose during exercise compared to 'Aware' (-21 ± 44 vs. -19 ± 43 mg/dL [-1.17 ± 2.44 vs. -1.05 ± 2.39 mmol/L], adjusted group difference of -4.2 [95% CI: -8.4 to 0.05] mg/dL [-0.23 95% CI: -0.47 to 0.003 mmol/L], P = 0.051). Individuals with IAH had higher proportion of days with hypoglycemic events <70 mg/dL[3.89 mmol/L] (≥15 minutes <70 mg/dL[<3.89 mmol/L]) both on exercise days (51% vs. 43%, P = 0.006) and sedentary days (48% vs. 30%, P = 0.001). The increased odds of experiencing a hypoglycemic event <70 mg/dL[<3.89 mmol/L] for individuals with IAH compared to 'Aware' did not differ significantly between exercise and sedentary days (interaction P = 0.36). CONCLUSION: Individuals with IAH have a higher underlying risk of hypoglycemia than 'Aware' individuals. Exercise does not appear to differentially increase risk for hypoglycemia during the activity, or in the subsequent 24-hours for IAH compared to Aware individuals with T1D.

Associations between daily step count classifications and continuous glucose monitoring metrics in adults with type 1 diabetes: analysis of the Type 1 Diabetes Exercise Initiative (T1DEXI) cohort.

AIMS/HYPOTHESIS: Adults with type 1 diabetes should perform daily physical activity to help maintain health and fitness, but the influence of daily step counts on continuous glucose monitoring (CGM) metrics are unclear. This analysis used the Type 1 Diabetes Exercise Initiative (T1DEXI) dataset to investigate the effect of daily step count on CGM-based metrics. METHODS: In a 4 week free-living observational study of adults with type 1 diabetes, with available CGM and step count data, we categorised participants into three groups-below (<7000), meeting (7000-10,000) or exceeding (>10,000) the daily step count goal-to determine if step count category influenced CGM metrics, including per cent time in range (TIR: 3.9-10.0 mmol/l), time below range (TBR: <3.9 mmol/l) and time above range (TAR: >10.0 mmol/l). RESULTS: A total of 464 adults with type 1 diabetes (mean±SD age 37±14 years; HbA1c 48.8±8.1 mmol/mol [6.6±0.7%]; 73% female; 45% hybrid closed-loop system, 38% standard insulin pump, 17% multiple daily insulin injections) were included in the study. Between-participant analyses showed that individuals who exceeded the mean daily step count goal over the 4 week period had a similar TIR (75±14%) to those meeting (74±14%) or below (75±16%) the step count goal (p>0.05). In the within-participant comparisons, TIR was higher on days when the step count goal was exceeded or met (both 75±15%) than on days below the step count goal (73±16%; both p<0.001). The TBR was also higher when individuals exceeded the step count goals (3.1%±3.2%) than on days when they met or were below step count goals (difference in means -0.3% [p=0.006] and -0.4% [p=0.001], respectively). The total daily insulin dose was lower on days when step count goals were exceeded (0.52±0.18 U/kg; p<0.001) or were met (0.53±0.18 U/kg; p<0.001) than on days when step counts were below the current recommendation (0.55±0.18 U/kg). Step count had a larger effect on CGM-based metrics in participants with a baseline HbA1c ≥53 mmol/mol (≥7.0%). CONCLUSIONS/INTERPRETATION: Our results suggest that, compared with days with low step counts, days with higher step counts are associated with slight increases in both TIR and TBR, along with small reductions in total daily insulin requirements, in adults living with type 1 diabetes. DATA AVAILABILITY: The data that support the findings reported here are available on the Vivli Platform (ID: T1-DEXI; https://doi.org/10.25934/PR00008428 ).

Factors Affecting Reproducibility of Change in Glucose During Exercise: Results From the Type 1 Diabetes and EXercise Initiative.

AIMS: To evaluate factors affecting within-participant reproducibility in glycemic response to different forms of exercise. METHODS: Structured exercise sessions ~30 minutes in length from the Type 1 Diabetes Exercise Initiative (T1DEXI) study were used to assess within-participant glycemic variability during and after exercise. The effect of several pre-exercise factors on the within-participant glycemic variability was evaluated. RESULTS: Data from 476 adults with type 1 diabetes were analyzed. A participant's change in glucose during exercise was reproducible within 15 mg/dL of the participant's other exercise sessions only 32% of the time. Participants who exercised with lower and more consistent glucose level, insulin on board (IOB), and carbohydrate intake at exercise start had less variability in glycemic change during exercise. Participants with lower mean glucose (P < .001), lower glucose coefficient of variation (CV) (P < .001), and lower % time <70 mg/dL (P = .005) on sedentary days had less variable 24-hour post-exercise mean glucose. CONCLUSIONS: Reproducibility of change in glucose during exercise was low in this cohort of adults with T1D, but more consistency in pre-exercise glucose levels, IOB, and carbohydrates may increase this reproducibility. Mean glucose variability in the 24 hours after exercise is influenced more by the participant's overall glycemic control than other modifiable factors.

Use of the Community-Derived Open-Source Automated Insulin Delivery Loop System in Type 2 Diabetes.

Background: No published data are available on the use of the community-derived open-source Loop hybrid closed-loop controller ("Loop") by individuals with type 2 diabetes (T2D). Methods: Through social media postings, we invited individuals with T2D currently using the Loop system to join an observational study. Thirteen responded of whom seven were eligible for the study, were using the Loop algorithm, and provided data. Results: Mean (±standard deviation) age was 61 ± 13 years, and mean body mass index was 31 ± 5 kg/m2. All but one participant were using noninsulin glucose-lowering medications. Self-reported mean hemoglobin A1c decreased from 7.3% ± 1.1% before starting Loop to 6.0% ± 0.5% on Loop. Time in range 70-180 mg/dL increased from 84% to 93%. The amount of time in hypoglycemia was extremely low before and with Loop (time <54 mg/dL was 0.04% ± 0.06% vs. 0.09% ± 0.07%, respectively). No severe hypoglycemia or diabetic ketoacidosis events were reported while using Loop. Conclusion: These data, though limited, suggest that the Loop system is likely to be effective when used by individuals with T2D and should be evaluated in large-scale studies. Clinical Trial Registration numbers: NCT05951569.

Patient reported outcomes (PROs) and user experiences of young children with type 1 diabetes using t:slim X2 insulin pump with control-IQ technology.

OBJECTIVE: Examine patient-reported outcomes (PROs) after the use of t:slim X2 insulin pump with Control-IQ technology (CIQ) in young children with type 1 diabetes. METHODS: Children with type 1 diabetes, ages 2 to < 6 years (n = 102), were randomly assigned 2:1 to either CIQ or standard care (SC) with pump or multiple daily injections (MDI) plus continuous glucose monitoring (CGM) for 13 weeks. Both groups were offered to use CIQ for an additional 13 weeks after the randomized control trial's (RCT) completion. Guardians completed PRO questionnaires at baseline, 13-, and 26-weeks examining hypoglycemia concerns, quality of life, parenting stress, and sleep. At 26 weeks, 28 families participated in user-experience interviews. Repeated measures analyses compared PRO scores between systems used. RESULT: Comparing CIQ vs SC, responses on all 5 PRO surveys favored the CIQ group, showing that CIQ was superior to SC at 26 weeks (p values < 0.05). User-experience interviews indicated significant benefits in optimized glycemic control overall and nighttime control (28 of 28 families endorsed). All but 2/28 families noted substantial reduction in management burden resulting in less mental burden and all but 4 stated that they wanted their children to continue using CIQ. CONCLUSIONS: Families utilizing CIQ experienced glycemic benefits coupled with substantial benefits in PROs, documented in surveys and interviews. Families utilizing CIQ had reduced hypoglycemia concerns and parenting stress, and improved quality of life and sleep. These findings demonstrate the benefit of CIQ in young children with type 1 diabetes that goes beyond documented glycemic benefit.

Beneficial Effects of Control-IQ Automated Insulin Delivery in Basal-Bolus and Basal-Only Insulin Users With Type 2 Diabetes.

The t:slim X2 insulin pump with Control-IQ technology (Control-IQ) advanced hybrid closed-loop automated insulin delivery system was evaluated in this prospective single-arm trial. Thirty adults with type 2 diabetes using the Control-IQ system showed substantial glycemic improvement with no increase in hypoglycemia. Mean time in range (70-180 mg/dL) improved 15%, representing an increase of 3.6 hours/day, and mean glucose decreased by 22 mg/dL.

A Comparison of Continuous Glucose Monitoring-Measured Time-in-Range 70-180 mg/dL Versus Time-in-Tight-Range 70-140 mg/dL.

Objective: To evaluate the relationship between continuous glucose monitoring (CGM)-measured time-in-range 70-180 mg/dL (TIR) and time-in-tight-range 70-140 mg/dL (TITR). Methods: TIR and TITR were calculated from CGM data collected using blinded or unblinded Dexcom sensors from 9 studies with 912 participants with type 1 diabetes (T1D) and 2 studies with 184 participants with type 2 diabetes (T2D). The TIR-TITR relationship was assessed overall and stratified by coefficient of variation (CV) and by time below range <70 mg/dL (TBR). Results: The correlation between TIR and TITR was 0.94. TITR was higher for a given TIR for T2D compared with T1D. However, after adjusting for the differences in CV or TBR, both of which were higher with T1D than T2D, the differences were minimized. The TIR-TITR relationship was nonlinear, with a higher ratio of TITR:TIR observed as TIR increased ranging from 0.42 when TIR was 20% to 0.66 when TIR was 80%. Similarly, as TITR increased, the ratio of TIR:TITR decreased, varying from 2.6 with TITR of 10% to 1.3 for TITR of 70%. The TIR-TITR relationship varied according to CV and TBR, such that the higher the CV or higher the amount of TBR the greater was TITR for a given TIR. Conclusions: TIR and TITR are highly correlated, although the relationship is nonlinear. With knowledge of TIR, TITR can be estimated with reasonable precision.

Time in Range Is Associated with Incident Diabetic Retinopathy in Adults with Type 1 Diabetes: A Longitudinal Study.

Abstract Objective: To evaluate the association between continuous glucose monitoring (CGM)-based time in various ranges and the subsequent development of diabetic retinopathy (incident DR) in adults with type 1 diabetes. Methods: Between June 2018 and March 2022, adults with type 1 diabetes with incident DR or no retinopathy (control) were identified. CGM data were collected retrospectively for up to 7 years before the date of eye examination defining incident DR or control. Associations between incident DR and CGM metrics were evaluated using logistic regression models. Results: This analysis included 71 adults with incident DR (mean age 27 years, 52% females, and mean diabetes duration 15 years) and 92 adults without DR (mean age 38 years, 48% females, and mean diabetes duration 20 years). Adjusting for age, diabetes duration, and CGM type, each 0.5% increase in glycated hemoglobin (HbA1c), 10 mg/dL increase in mean glucose, 5% decrease in time in target range 70-180 mg/dL (TIR), 5% decrease in time in tight target range 70-140 mg/dL (TITR), and 5% increase in time above 180 mg/dL (TAR) were associated with 24%, 22%, 18%, 28%, and 20% increase in odds of incident DR, respectively. Spearman correlations of TIR, TITR, TAR, and mean glucose with each other were all ≥0.97. Conclusion: Similar to HbA1c, TIR, TITR, TAR, and mean glucose were associated with increased risk for incident DR in adults with type 1 diabetes. These CGM metrics are highly correlated indicating that they provide similar information on glycemic control and diabetic retinopathy risk.

Comprehensive Telehealth Model to Support Diabetes Self-Management.

Importance: As the number of patients with diabetes continues to increase in the United States, novel approaches to clinical care access should be considered to meet the care needs for this population, including support for diabetes-related technology. Objective: To evaluate a virtual clinic to facilitate comprehensive diabetes care, support continuous glucose monitoring (CGM) integration into diabetes self-management, and provide behavioral health support for diabetes-related issues. Design, Setting, and Participants: This cohort study was a prospective, single-arm, remote study involving adult participants with type 1 or type 2 diabetes who were referred through community resources. The study was conducted virtually from August 24, 2020, to May 26, 2022; analysis was conducted at the clinical coordinating center. Intervention: Training and education led by a Certified Diabetes Care and Education Specialist for CGM use through a virtual endocrinology clinic structure, which included endocrinologists and behavioral health team members. Main Outcomes and Measures: Main outcomes included CGM-measured mean glucose level, coefficient of variation, and time in range (TIR) of 70 to 180 mg/dL, time with values greater than 180 mg/dL or 250 mg/dL, and time with values less than 70 mg/dL or 54 mg/dL. Hemoglobin A1c was measured at baseline and at 12 and 24 weeks. Results: Among the 234 participants, 160 had type 1 diabetes and 74 had type 2 diabetes. The mean (SD) age was 47 (14) years, 123 (53%) were female, and median diabetes duration was 20 years. Median (IQR) CGM use over 6 months was 96% (91%-98%) for participants with type 1 diabetes and 94% (85%-97%) for those with type 2 diabetes. Mean (SD) hemoglobin A1c (HbA1c) in those with type 1 diabetes decreased from 7.8% (1.6%) at baseline to 7.1% (1.0%) at 3 months and 7.1% (1.0%) at 6 months (mean change from baseline to 6 months, -0.6%, 95% CI, -0.8% to -0.5%; P < .001), with an 11% mean TIR increase over 6 months (95% CI, 9% to 14%; P < .001). Mean HbA1c in participants with type 2 diabetes decreased from 8.1% (1.7%) at baseline to 7.1% (1.0%) at 3 months and 7.1% (0.9%) at 6 months (mean change from baseline to 6 months, -1.0%; 95% CI, -1.4% to -0.7%; P < .001), with an 18% TIR increase over 6 months (95% CI, 13% to 24%; P < .001). In participants with type 1 diabetes, mean percentage of time with values less than 70 mg/dL and less than 54 mg/dL decreased over 6 months by 0.8% (95% CI, -1.2% to -0.4%; P = .001) and by 0.3% (95% CI, -0.5% to -0.2%, P < .001), respectively. In the type 2 diabetes group, hypoglycemia was rare (mean [SD] percentage of time <70 mg/dL, 0.5% [0.6%]; and <54 mg/dL, 0.07% [0.14%], over 6 months). Conclusions and Relevance: Results from this cohort study demonstrated clinical benefits associated with implementation of a comprehensive care model that included diabetes education. This model of care has potential to reach a large portion of patients with diabetes, facilitate diabetes technology adoption, and improve glucose control.

Testing the Real-World Accuracy of the Dexcom G6 Pro CGM During the Insulin-Only Bionic Pancreas Pivotal Trial.

Continuous glucose monitors (CGMs) have transformed the way people with type 1 diabetes can self-monitor glucose levels. Past studies have evaluated the accuracy of CGMs in clinic-based studies, but few have analyzed their accuracy in real-world settings. The Insulin-Only Bionic Pancreas Trial provided the opportunity to assess real-world accuracy of the blinded Dexcom G6 Pro sensor over the first 48-60 h of wear using a blood glucose meter (BGM) as a comparator for 1073 CGM-BGM pairs across 53 participants. The mean absolute relative difference (MARD) was 11.0% over a median period of 50 h (range 47-79 h). The MARD was 13.6% in the first 12 h, 10.5% in hours 12-24, and 10.1% after the first 24 h. These results are comparable with accuracy shown previously with laboratory-based measurements and provide real-world evidence of Dexcom G6 Pro accuracy, which improved after the first 12 h and then remained stable thereafter. Clinical Trial Registry: clinicaltrials.gov; NCT04200313.

Automated Insulin Delivery with Remote Real-Time Continuous Glucose Monitoring for Hospitalized Patients with Diabetes: A Multicenter, Single-Arm, Feasibility Trial.

Introduction: Multiple daily injection insulin therapy frequently fails to meet hospital glycemic goals and is prone to hypoglycemia. Automated insulin delivery (AID) with remote glucose monitoring offers a solution to these shortcomings. Research Design and Methods: In a single-arm multicenter pilot trial, we tested the feasibility, safety, and effectiveness of the Omnipod 5 AID System with real-time continuous glucose monitoring (CGM) for up to 10 days in hospitalized patients with insulin-requiring diabetes on nonintensive care unit medical-surgical units. Primary endpoints included the proportion of time in automated mode and percent time-in-range (TIR 70-180 mg/dL) among participants with >48 h of CGM data. Safety endpoints included incidence of severe hypoglycemia and diabetes-related ketoacidosis (DKA). Additional glycemic endpoints, CGM accuracy, and patient satisfaction were also explored. Results: Twenty-two participants were enrolled; 18 used the system for a total of 96 days (mean 5.3 ± 3.1 days per patient), and 16 had sufficient CGM data required for analysis. Median percent time in automated mode was 95% (interquartile range 92%-98%) for the 18 system users, and the 16 participants with >48 h of CGM data achieved an overall TIR of 68% ± 16%, with 0.17% ± 0.3% time <70 mg/dL and 0.06% ± 0.2% time <54 mg/dL. Sensor mean glucose was 167 ± 21 mg/dL. There were no DKA or severe hypoglycemic events. All participants reported satisfaction with the system at study end. Conclusions: The use of AID with a disposable tubeless patch-pump along with remote real-time CGM is feasible in the hospital setting. These results warrant further investigation in randomized trials.

Low-Dose 0.01% Atropine Eye Drops vs Placebo for Myopia Control: A Randomized Clinical Trial.

Importance: Controlling myopia progression is of interest worldwide. Low-dose atropine eye drops have slowed progression in children in East Asia. Objective: To compare atropine, 0.01%, eye drops with placebo for slowing myopia progression in US children. Design, Setting, and Participants: This was a randomized placebo-controlled, double-masked, clinical trial conducted from June 2018 to September 2022. Children aged 5 to 12 years were recruited from 12 community- and institution-based practices in the US. Participating children had low to moderate bilateral myopia (-1.00 diopters [D] to -6.00 D spherical equivalent refractive error [SER]). Intervention: Eligible children were randomly assigned 2:1 to 1 eye drop of atropine, 0.01%, nightly or 1 drop of placebo. Treatment was for 24 months followed by 6 months of observation. Main Outcome and Measures: Automated cycloplegic refraction was performed by masked examiners. The primary outcome was change in SER (mean of both eyes) from baseline to 24 months (receiving treatment); other outcomes included change in SER from baseline to 30 months (not receiving treatment) and change in axial length at both time points. Differences were calculated as atropine minus placebo. Results: A total of 187 children (mean [SD] age, 10.1 [1.8] years; age range, 5.1-12.9 years; 101 female [54%]; 34 Black [18%], 20 East Asian [11%], 30 Hispanic or Latino [16%], 11 multiracial [6%], 6 West/South Asian [3%], 86 White [46%]) were included in the study. A total of 125 children (67%) received atropine, 0.01%, and 62 children (33%) received placebo. Follow-up was completed at 24 months by 119 of 125 children (95%) in the atropine group and 58 of 62 children (94%) in the placebo group. At 30 months, follow-up was completed by 118 of 125 children (94%) in the atropine group and 57 of 62 children (92%) in the placebo group. At the 24-month primary outcome visit, the adjusted mean (95% CI) change in SER from baseline was -0.82 (-0.96 to -0.68) D and -0.80 (-0.98 to -0.62) D in the atropine and placebo groups, respectively (adjusted difference = -0.02 D; 95% CI, -0.19 to +0.15 D; P = .83). At 30 months (6 months not receiving treatment), the adjusted difference in mean SER change from baseline was -0.04 D (95% CI, -0.25 to +0.17 D). Adjusted mean (95% CI) changes in axial length from baseline to 24 months were 0.44 (0.39-0.50) mm and 0.45 (0.37-0.52) mm in the atropine and placebo groups, respectively (adjusted difference = -0.002 mm; 95% CI, -0.106 to 0.102 mm). Adjusted difference in mean axial elongation from baseline to 30 months was +0.009 mm (95% CI, -0.115 to 0.134 mm). Conclusions and Relevance: In this randomized clinical trial of school-aged children in the US with low to moderate myopia, atropine, 0.01%, eye drops administered nightly when compared with placebo did not slow myopia progression or axial elongation. These results do not support use of atropine, 0.01%, eye drops to slow myopia progression or axial elongation in US children. Trial Registration: ClinicalTrials.gov Identifier: NCT03334253.

Psychosocial Impact of the Insulin-Only iLet Bionic Pancreas for Adults, Youth, and Caregivers of Youth with Type 1 Diabetes.

Objective: To evaluate the psychosocial impact and user experience for the insulin-only configuration of iLet bionic pancreas (BP) in persons 6-83 years years of age with type 1 diabetes. Research Design and Methods: In this multicenter, randomized controlled, 13-week trial, 275 adults (221 randomly assigned to the BP group and 54 to the standard of care [SC] group) and 165 youth and their caregivers (112 randomly assigned to the BP group and 53 to the SC group) completed psychosocial questionnaires at baseline, mid-study, and the end of the trial. Results: In all age groups, most participants would recommend using the BP, including those with previous experience using automated insulin delivery devices. Similarly, the vast majority of participants reported a high level of perceived benefits and a low number of perceived burdens. Adult participants reported significant decreases in the fear of hypoglycemia and in diabetes-specific emotional distress, as well as improvements in their perceived well-being. Conclusion: Findings demonstrate acceptability, reduced burden, and positive psychosocial outcomes for adults. Children and teenagers also report high acceptability and reduced burden, but less clear improvements in psychosocial outcomes. Clinical Trial Registration Number: NCT04200313.

The Type 1 Diabetes and EXercise Initiative: Predicting Hypoglycemia Risk During Exercise for Participants with Type 1 Diabetes Using Repeated Measures Random Forest.

Objective: Exercise is known to increase the risk for hypoglycemia in type 1 diabetes (T1D) but predicting when it may occur remains a major challenge. The objective of this study was to develop a hypoglycemia prediction model based on a large real-world study of exercise in T1D. Research Design and Methods: Structured study-specified exercise (aerobic, interval, and resistance training videos) and free-living exercise sessions from the T1D Exercise Initiative study were used to build a model for predicting hypoglycemia, a continuous glucose monitoring value <70 mg/dL, during exercise. Repeated measures random forest (RMRF) and repeated measures logistic regression (RMLR) models were constructed to predict hypoglycemia using predictors at the start of exercise and baseline characteristics. Models were evaluated with area under the receiver operating characteristic curve (AUC) and balanced accuracy. Results: RMRF and RMLR had similar AUC (0.833 vs. 0.825, respectively) and both models had a balanced accuracy of 77%. The probability of hypoglycemia was higher for exercise sessions with lower pre-exercise glucose levels, negative pre-exercise glucose rates of change, greater percent time <70 mg/dL in the 24 h before exercise, and greater pre-exercise bolus insulin-on-board (IOB). Free-living aerobic exercises, walking/hiking, and physical labor had the highest probability of hypoglycemia, while structured exercises had the lowest probability of hypoglycemia. Conclusions: RMRF and RMLR accurately predict hypoglycemia during exercise and identify factors that increase the risk of hypoglycemia. Lower glucose, decreasing levels of glucose before exercise, and greater pre-exercise IOB largely predict hypoglycemia risk in adults with T1D.