Hybrid Closed-loop Therapy Research Articles

Do hybrid closed loop insulin pump systems improve glycemic control and reduce hospitalizations in poorly controlled type 1 diabetes?

Hybrid closed-loop (HCL) systems improve glycemic control in type 1 diabetes mellitus (T1D), but their effectiveness in young, poorly controlled populations is notestablished and requires study. A pre-post study was performed using electronic health records of patients 3-24 years with baseline HbA1c≥9 % prescribed HCL within the New York City Health+Hospitals System assessing HbA1c levels and hospitalizations before and after HCL initiation and factors associated with achieving HbA1c<9 % after HCLinitiation. Of 47 children and adolescents who met inclusion criteria, 4.68 % female, 95.72 % non-White, and 82.22 % covered by public insurance, with a baseline average HbA1c10.6 % (2.28 IQR). The most prevalent pump type wasOmnipod 5 (70.21 %). The HbA1c was significantly lowerinthe postperiod than baseline (HbA1c before=median 10.6 (IQR2.28), HbA1c after=median 9.33 (IQR 2.97), difference 1.00 (IQR 1.64), p<0.05) with a decrease in median diabetes-related hospitalizations (preperiod 1.00 (IQR 1.00), postperiod 0.00 (IQR 1.00), difference-1.00, IQR 2, p<0.05). Lower baseline HbA1c levels made reaching HbA1c<9 % more likely. Multivariable analysis showed thatthe odds of having HbA1c of <9 % was 2.1 times less likely for every one point increase in baseline HbA1c and 12.5 times less likely for those with a pump at (p<0.05). HCL therapy improved glycemic control and decreased diabetes-related hospitalizations in youth with poorly controlled T1DM. Higher baseline HbA1c levels predicted less success with HCL therapy so those who standto benefit most benefit least.

Use of continuous glucose monitoring and hybrid closed-loop therapy in pregnancy.

Continuous glucose monitoring (CGM) has led to a paradigm shift in the management of pregnant women with type 1 diabetes (T1D), with improved glycaemic control, less hypoglycaemia and fewer pregnancy complications. Data on CGM use in pregnant women with type 2 diabetes (T2D) are limited. A large randomized controlled trial (RCT) on CGM use in people with T2D in pregnancy is ongoing. Small studies on CGM use in women with gestational diabetes (GDM) have suggested improved glycaemic control and better qualification when insulin is needed. However, none of these studies was powered to evaluate pregnancy outcomes. Several large RCTs are ongoing in women with GDM. In addition to CGM, other technologies, such as advanced hybrid closed-loop (AHCL) systems have further improved glycaemic management in people with T1D. AHCL therapy adapts insulin delivery via a predictive algorithm integrated with CGM and an insulin pump. A large RCT with the AHCL CamAPS® FX demonstrated a 10% increase in time in range compared to standard insulin therapy in a pregnant population with T1D. Recently, an RCT of an AHCL system not approved for use in pregnancy (780G MiniMed) has also demonstrated additional benefits of AHCL therapy compared to standard insulin therapy, with improved time in range overnight, less hypoglycaemia and improved treatment satisfaction. More evidence is needed on the impact of AHCL therapy on maternal and neonatal outcomes and on which glycaemic targets with CGM should be used in pregnant women with T2D and GDM. We review the current evidence on the use of CGM and AHCL therapy in pregnancy.

Closed-Loop Therapy and Sleep in Young People Newly Diagnosed With T1D and Their Parents.

A diagnosis of type 1 diabetes in a young person can create vulnerability for sleep. Historically it has been rare for young people to be offered a closed-loop system soon after diagnosis meaning that studies examining sleep under these circumstances in comparison with standard treatment have not been possible. In this study, we examine sleep in young people (and their parents) who were provided with hybrid closed-loop therapy at diagnosis of type 1 diabetes versus those who receive standard treatment over a 2-year period. The sample comprised 97 participants (mean age = 12.0 years; SD = 1.7) from a multicenter, open-label, randomized, parallel trial, where young people were randomized to either hybrid closed-loop insulin delivery or standard care at diagnosis. Sleep was measured using actigraphy and the Pittsburgh Sleep Quality Index (PSQI) in the young people, and using the PSQI in parents. Sleep in young people using hybrid closed-loop insulin delivery did not differ significantly compared with those receiving standard care (although there were nonsignificant trends for better sleep in the closed-loop group for 4 of the 5 sleep actigraphy measures and PSQI). Similarly, there were nonsignificant differences for sleep between the groups at 24 months (with mixed direction of effects). This study assessed for the first time sleep in young people using a closed-loop system soon after diagnosis. Although sleep was not significantly different for young people using closed-loop insulin delivery as compared with those receiving standard care, the direction of effects of the nonsignificant results indicates a possible tendency for better sleep quality in the hybrid closed-loop insulin delivery group at the beginning of the treatment.

Advanced Hybrid Closed-Loop Therapy Compared With Standard Insulin Therapy Intrapartum and Early Postpartum in Women With Type 1 Diabetes: A Secondary Observational Analysis From the CRISTAL Randomized Controlled Trial.

To determine efficacy and safety of intrapartum and early postpartum advanced hybrid closed-loop (AHCL) therapy compared with standard insulin therapy in pregnant women with type 1 diabetes (T1D). CRISTAL was a double-arm, open-label, randomized controlled trial performed in Belgium and the Netherlands that assigned 95 pregnant participants with T1D 1:1 to a MiniMed 780G AHCL system (n = 46) or standard insulin therapy (n = 49). This prespecified, secondary observational analysis focused on differences in glycemic control and safety outcomes between participants from the original AHCL group who continued AHCL intrapartum (n = 27) and/or early postpartum (n = 37, until hospital discharge) and those from the original standard insulin therapy group using standard insulin therapy intrapartum (n = 45) and/or early postpartum (n = 34). Of the 43 and 46 participants in the AHCL and standard insulin therapy groups, respectively, completing the trial, 27 (62.8%) in the AHCL group continued AHCL and 45 in the standard insulin therapy group (97.8%) continued standard insulin therapy intrapartum. Compared with standard insulin therapy, intrapartum AHCL was associated with more time in range 3.5-7.8 mmol/L (71.5 ± 17.7% vs. 63.1 ± 17.0%, P = 0.030) and numerically lower time above range >7.8 mmol/L (27.3 ± 17.4% vs. 35.3 ± 17.5%, P = 0.054), without increases in time below range <3.5 mmol/L (1.1 ± 2.4% vs. 1.5 ± 2.3%, P = 0.146). Early postpartum, 37 (86.0%) participants randomized to AHCL continued AHCL, with a median increase in insulin-to-carbohydrate ratios of 67% (interquartile range -14 to 126). Similar tight glycemic control (3.9-10.0 mmol/L: 86.8 ± 6.7% vs. 83.8 ± 8.1%, P = 0.124) was observed with AHCL versus standard insulin therapy. No severe hypoglycemia or diabetic ketoacidosis was reported in either group. AHCL is effective in maintaining tight glycemic control intrapartum and early postpartum and can be safely continued during periods of rapidly changing insulin requirements.

Outcomes from hybrid closed-loop therapy in children and young people with type 1 diabetes at leeds children's hospital

Outcomes from hybrid closed-loop therapy in children and young people with type 1 diabetes at leeds children's hospital

Advanced hybrid closed-loop therapy in adults with type 1 diabetes: outcomes in a real-world setting

Advanced hybrid closed-loop therapy in adults with type 1 diabetes: outcomes in a real-world setting

Hybrid Closed Loop in Adults With Type 1 Diabetes and Severely Impaired Hypoglycemia Awareness.

Benefits of hybrid closed-loop (HCL) systems in a high-risk group with type 1 diabetes and impaired awareness of hypoglycemia (IAH) have not been well-explored. Adults with Edmonton HYPO scores ≥1047 were randomized to 26-weeks HCL (MiniMed™ 670G) vs standard therapy (multiple daily injections or insulin pump) without continuous glucose monitoring (CGM) (control). Primary outcome was percentage CGM time-in-range (TIR; 70-180 mg/dL) at 23 to 26 weeks post-randomization. Major secondary endpoints included magnitude of change in counter-regulatory hormones and autonomic symptom responses to hypoglycemia at 26-weeks post-randomization. A post hoc analysis evaluated glycemia risk index (GRI) comparing HCL with control groups at 26 weeks post-randomization. Nine participants (median [interquartile range (IQR)] age 51 [41, 59] years; 44% male; enrolment HYPO score 1183 [1058, 1308]; Clarke score 6 [6, 6]; n = 5 [HCL]; n = 4 [control]) completed the study. Time-in-range was higher using HCL vs control (70% [68, 74%] vs 48% [44, 50%], P = .014). Time <70 mg/dL did not differ (HCL 3.8% [2.7, 3.9] vs control 6.5% [4.3, 8.6], P = .14) although hypoglycemia episode duration was shorter (30 vs 50 minutes, P < .001) with HCL. Glycemia risk index was lower with HCL vs control (38.1 [30.0, 39.2] vs 70.8 [58.5, 72.4], P = .014). Following 6 months of HCL use, greater dopamine (24.0 [12.3, 27.6] vs -18.5 [-36.5, -4.8], P = .014), and growth hormone (6.3 [4.6, 16.8] vs 0.5 [-0.8, 3.0], P = .050) responses to hypoglycemia were observed. Six months of HCL use in high-risk adults with severe IAH increased glucose TIR and improved GRI without increased hypoglycemia, and partially restored counter-regulatory responses. ACTRN12617000520336.

Efficacy of the hybrid closedloop insulin delivery system in children and adolescents with type 1 diabetes: a meta-analysis with trial sequential analysis.

The aim of this study was to assess the efficacy and safety of hybrid closed-loop (HCL) systems for insulin delivery in children and adolescents with type 1 diabetes (T1D). We searched Embase, PubMed, and Cochrane Library for randomized controlled trials (RCTs) published until March 2023 comparing the HCL therapy with control therapies for children and adolescents with T1D. We computed weighted mean differences (WMDs) for continuous outcomes and risk ratios (RRs) with 95% confidence intervals (CIs) for binary endpoints. Four RCTs and 501 patients were included, of whom 323 were randomized to HCL therapy. Compared with control therapies, HCL significantly improved the period during which glucose level was 70-180 mg/dL (WMD 10.89%, 95% CI 8.22-13.56%) and the number of participants with glycated hemoglobin (HbA1c) level < 7% (RR 2.61, 95% CI 1.29-5.28). Also, HCL significantly reduced the time during which glucoselevel was > 180 mg/dL (WMD-10.46%, 95% CI-13.99 to-6.93%) and the mean levels of glucose (WMD-16.67 mg/dL, 95% CI-22.25 to-11.09 mg/dL) and HbA1c (WMD-0.50%, 95% CI-0.68 to-0.31). There were no significant differences between therapies regarding time during which glucose level was < 70 mg/dL or <54 mg/dL or number of episodes of ketoacidosis, hyperglycemia, and hypoglycemia. In this meta-analysis, HCL compared with control therapies was associated with improved time in range and HbA1c control in children and adolescents with T1D and a similar profile of side effects. These findings support the efficacy of HCL in the treatment of T1D in this population.

Automated closed-loop insulin delivery for the management of type 1 diabetes during pregnancy: the AiDAPT RCT

Background There are over 2000 pregnancies annually in women with type 1 diabetes in the UK. Despite recent improvements in diabetes technology, most women cannot achieve and maintain the recommended pregnancy glucose targets. Thus, one in two babies experience complications requiring neonatal care unit admission. Recent studies demonstrate that hybrid closed-loop therapy, in which algorithms adjust insulin delivery according to continuous glucose measurements, is effective for managing type 1 diabetes outside of pregnancy, but efficacy during pregnancy is unclear. Objective To examine the clinical efficacy of hybrid closed-loop compared to standard insulin therapy in pregnant women with type 1 diabetes. Design A multicentre, parallel-group, open-label, randomised, controlled trial in pregnant women with type 1 diabetes. Setting Nine antenatal diabetes clinics in England, Scotland and Northern Ireland. Participants Pregnant women with type 1 diabetes and above-target glucose levels, defined as glycated haemoglobin A1c of ≥ 48 mmol/mol (6.5%) in early pregnancy. Interventions A hybrid closed-loop system compared to standard insulin delivery (via insulin pump or multiple daily injections) with continuous glucose monitoring. Outcome measures The primary outcome is the difference between the intervention and control groups in percentage time spent in the pregnancy glucose target range (3.5–7.8 mmol/l) as measured by continuous glucose monitoring from 16 weeks’ gestation until delivery. Secondary outcomes include overnight time in range, time above range (&gt; 7.8 mmol/l), glycated haemoglobin A1c, safety outcomes (diabetic ketoacidosis, severe hypoglycaemia, adverse device events), psychosocial functioning obstetric and neonatal outcomes. Results The percentage of time that maternal glucose levels were within target range was higher with closed-loop than standard insulin therapy: 68.2 ± 10.5 in closed-loop and 55.6 ± 12.5 in the control group (mean‑adjusted difference 10.5 percentage points, 95% confidence interval 7.0 to 14.0; p &lt; 0.001). Results were consistent in secondary outcomes, with less time above range (−10.2%, 95% confidence interval −13.8 to −6.6%; p &lt; 0.001), higher overnight time in range (12.3%, 95% confidence interval 8.3 to 16.2%; p &lt; 0.001) and lower glycated haemoglobin A1c (−0.31%, 95% confidence interval −0.50 to −0.12%; p &lt; 0.002) all favouring closed-loop. The treatment effect was apparent from early pregnancy and consistent across clinical sites, maternal glycated haemoglobin A1c categories and previous insulin regimen. Maternal glucose improvements were achieved with 3.7 kg less gestational weight gain and without additional hypoglycaemia or total daily insulin dose. There were no unanticipated safety problems (six vs. five severe hypoglycaemia cases, one diabetic ketoacidosis per group) and seven device-related adverse events associated with closed-loop. There were no between-group differences in patient-reported outcomes. There was one shoulder dystocia in the closed-loop group and four serious birth injuries, including one neonatal death in the standard care group. Limitations Our results cannot be extrapolated to closed-loop systems with higher glucose targets, and our sample size did not provide definitive data on maternal and neonatal outcomes. Conclusions Hybrid closed-loop therapy significantly improved maternal glycaemia during type 1 diabetes pregnancy. Our results support National Institute for Health and Care Excellence guideline recommendations that hybrid closed-loop therapy should be offered to all pregnant women with type 1 diabetes. Future work Future trials should examine the effectiveness of hybrid closed-loop started before pregnancy, or as soon as possible after pregnancy confirmation. Trial registration This trial is registered as ISRCTN56898625. Funding This award was funded by the National Institute of Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 16/35/01) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 7. See the NIHR Funding and Awards website for further award information. Dexcom supplied the continuous glucose monitoring systems used by AiDAPT intervention- and control-arm participants at reduced cost.

Randomized Trial of Assisted Hybrid Closed-Loop Therapy Versus Sensor-Augmented Pump Therapy in Pregnancy.

Objective: Examine gestational safety, glycemic and health outcomes, of a hybrid closed-loop (HCL) system without pregnancy-specific glucose targets. Research Design: This was a pilot feasibility investigator-initiated, two-site, single-blind, randomized controlled trial of sensor-augmented pump therapy (SAPT) versus HCL therapy in type 1 diabetes pregnancies. Participants were enrolled in the first trimester and randomized at 14-18 weeks of gestation and used SAPT or HCL until 4-6 weeks postpartum. We compared continuous glucose monitoring (CGM) metrics, severe hypoglycemia (SH), diabetic ketoacidosis (DKA), adverse skin reactions, and pregnancy outcomes between groups. Results: Baseline characteristics were similar between groups (n = 11 HCL and n = 12 SAPT). There was no SH or DKA episode after randomization. Time spent <54 mg/dL did not differ between groups. Time spent <63 mg/dL decreased in both groups, significantly in the HCL group (3.5% [1.3% standard error] second trimester and 2.8% [1.3%] third trimester vs. 7.9% [1.3%] run-in phase, P < 0.05 for both). Mean sensor glucose was lower with SAPT compared to HCL therapy in the third trimester (119 [4] mg/dL SAPT vs. 132 [4] mg/dL HCL, P < 0.05). Third trimester time-in-range (TIR; 63-140 mg/dL) increased with SAPT (68.2% [3.1%] vs. 64.3% [3.1%] run-in phase, P < 0.05). Gestational health outcomes did not differ between groups. The HCL group used assistive techniques, such as fake carbohydrate boluses and exiting HCL overnight. Conclusions: CGM within group differences were seen for time <63 mg/dL favoring HCL therapy and TIR favoring SAPT (third trimester vs. baseline). Safety and adverse pregnancy outcomes were similar between groups.

Clinical Outcomes with MiniMedTM 780G Advanced Hybrid Closed-Loop Therapy in 2- to 6-Year-Old Children with Type 1 Diabetes.

Advanced hybrid closed-loop (AHCL) therapy with the Medtronic MiniMed™ 780G system improves glycemia; however, the clinical outcomes in younger children remain less established. This pilot study aimed to explore the continuous glucose monitoring (CGM) metrics in very young children on AHCL. Children between 2 and 7 years of age and on insulin pump therapy were recruited. A 2-week phase in manual mode was followed by a 6-week AHCL phase. CGM metrics were analyzed to review glycemic outcomes. Out of 11 participants enrolled [mean (standard deviation [SD]) age 5.3 (0.8) years], 10 completed the study. Time in closed loop was 96.7 (3.9)%. In AHCL, participants had a mean (SD) time in range of 72.6 (7.4)% and spent 3.0 (1.74)% and 0.63 (0.46)% in time <70 and <54 mg/dL, respectively. AHCL is a feasible option for management of young children with type 1 diabetes.

Diabetic Ketoacidosis at Onset of Type 1 Diabetes and Glycemic Outcomes with Closed-Loop Insulin Delivery.

The presence of diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes (T1D) is associated with higher glycated hemoglobin levels over time. We evaluated whether hybrid-closed loop (HCL) therapy from onset of T1D could prevent the adverse impact of DKA at diagnosis on long-term glycemic outcomes. This was a posthoc analysis from 51 adolescents using HCL from diagnosis of T1D as part of the CLOuD trial (NCT02871089). We compared glycemic and insulin metrics between adolescents with (n = 17) and without (n = 34) DKA at diagnosis. Participants with and without DKA at diagnosis had similar time in target glucose range 3.9-10.0 mmol/L (70-180 mg/dL), time below range (<3.9 mmol/L, <70 mg/dL) and HbA1c at 6, 12, and 24 months. While insulin requirements at 6 months were higher in those with DKA at diagnosis, this was not statistically significant after adjusting for bodyweight. Residual C-peptide secretion was similar between groups. We conclude that HCL therapy may mitigate against the negative glycemic effects of DKA at T1D diagnosis.

Real-World Evidence of Off-Label Use of Commercially Automated Insulin Delivery Systems Compared to Multiple Daily Insulin Injections in Pregnancies Complicated by Type 1 Diabetes.

Aims: To compare glycemic control and maternal-fetal outcomes of women with type 1 diabetes (T1D) using hybrid closed loop (HCL) versus multiple daily insulin injections (MDI) plus continuous glucose monitoring. Methods: Multicenter prospective cohort study of pregnant women with T1D in Spain. We evaluated HbA1c and time spent within (TIR), below (TBR), and above (TAR) the pregnancy-specific glucose range of 3.5-7.8 mmol/L. Adjusted models were performed for adverse pregnancy outcomes, including baseline maternal characteristics and center. Results: One hundred twelve women were included (HCL n = 59). Women in the HCL group had a longer duration of diabetes and higher rates of prepregnancy care. There was no between-group difference in HbA1c in any trimester. However, in the second trimester, MDI users had a greater decrease in HbA1c (-6.12 ± 9.06 vs. -2.16 ± 7.42 mmol/mol, P = 0.031). No difference in TIR (3.5-7.8 mmol/L) and TAR was observed between HCL and MDI users, but with a higher total insulin dose in the second trimester [+0.13 IU/kg·day)]. HCL therapy was associated with increased maternal weight gain during pregnancy (βadjusted = 3.20 kg, 95% confidence interval [CI] 0.90-5.50). Regarding neonatal outcomes, newborns of HCL users were more likely to have higher birthweight (βadjusted = 279.0 g, 95% CI 39.5-518.5) and macrosomia (ORadjusted = 3.18, 95% CI 1.05-9.67) compared to MDI users. These associations disappeared when maternal weight gain or third trimester HbA1c was included in the models. Conclusions: In a real-world setting, HCL users gained more weight during pregnancy and had larger newborns than MDI users, while achieving similar glycemic control in terms of HbA1c and TIR.

Postprandial Glucose Excursions with Ultra-Rapid Insulin Analogs in Hybrid Closed-Loop Therapy for Adults with Type 1 Diabetes.

Objective: To evaluate postprandial glucose control when applying (1) faster-acting insulin aspart (Fiasp) compared to insulin aspart and (2) ultra-rapid insulin lispro (Lyumjev) compared to insulin lispro using the CamAPS FX hybrid closed-loop algorithm. Research Design and Methods: We undertook a secondary analysis of postprandial glucose excursions from two double-blind, randomized, crossover hybrid closed-loop studies contrasting Fiasp to standard insulin aspart, and Lyumjev to standard insulin lispro. Endpoints included incremental area under curve (iAUC)-2h, iAUC-4h, 4 h postprandial time in target range, time above range, and time below range. It was approved by independent research ethics committees. Results: Two trials with 8 weeks of data from 51 adults with type 1 diabetes were analyzed and 7137 eligible meals were included. During Lyumjev compared with insulin lispro, iAUC-2h and iAUC-4h were significantly decreased following breakfast (mean difference 92 mmol/L per 2 h (95% confidence interval [CI]: 56 to 127); P < 0.001 and 151 mmol/L per 4 h (95% CI: 74 to 229); P < 0.001, respectively) and the evening meal (P < 0.001 and P = 0.011, respectively). Mean time in target range (3.9-10.0 mmol/L) for 4 h postprandially significantly increased during Lyumjev with a mean difference of 6.7 percentage points (95% CI: 3.3 to 10) and 5.7 percentage points (95% CI: 1.4 to 9.9) for breakfast and evening meal, respectively. In contrast, there were no significant differences in iAUC-2h, iAUC-4h, and the other measures of postprandial glucose control between insulin aspart and Fiasp during breakfast, lunch, and evening meal (P > 0.05). Conclusion: The use of Lyumjev with CamAPS FX closed-loop system improved postprandial glucose excursions compared with insulin lispro, while the use of Fiasp did not provide any advantage compared with insulin aspart. Clinical Trial Registration numbers: NCT04055480, NCT05257460.

Guidelines of the Polish Society of Pediatric Endocrinology and Diabetology and Pediatric Section of Diabetes Poland on insulin therapy using hybrid closed-loop systems in children and adolescents with diabetes in Poland.

Currently, hybrid closed loop (HCL) systems represent the most advantageous therapeutic option for people with diabetes requiring intensive insulin therapy. They make it possible to achieve optimal metabolic control of the disease in any age group while improving the quality of life of children and adolescents with diabetes and their families. Therefore, we present recommendations for the use of HCL systems in children and adolescents focusing on systems currently available in Poland. These systems should be the first choice in terms of method of insulin therapy in the paediatric population. They can be implemented at any stage of diabetes management. These recommendations are based on scientific evidence and experts' experience. They include principles for the initiation, optimisation, and ongoing management of HCL therapy, as well as the required HCL-related education.

Hybrid closed-loop therapy: the calm before the storm

Hybrid closed-loop therapy: the calm before the storm

Automated Insulin Delivery in Women with Pregnancy Complicated by Type 1 Diabetes

BackgroundHybrid closed-loop insulin therapy has shown promise for management of type 1 diabetes during pregnancy; however, its efficacy is unclear.MethodsIn this multicenter, controlled trial, we randomly assigned pregnant women with type 1 diabetes and a glycated hemoglobin level of at least 6.5% at nine sites in the United Kingdom to receive standard insulin therapy or hybrid closed-loop therapy, with both groups using continuous glucose monitoring. The primary outcome was the percentage of time in the pregnancy-specific target glucose range (63 to 140 mg per deciliter [3.5 to 7.8 mmol per liter]) as measured by continuous glucose monitoring from 16 weeks’ gestation until delivery. Analyses were performed according to the intention-to-treat principle. Key secondary outcomes were the percentage of time spent in a hyperglycemic state (glucose level >140 mg per deciliter), overnight time in the target range, the glycated hemoglobin level, and safety events.ResultsA total of 124 participants with a mean (±SD) age of 31.1±5.3 years and a mean baseline glycated hemoglobin level of 7.7±1.2% underwent randomization. The mean percentage of time that the maternal glucose level was in the target range was 68.2±10.5% in the closed-loop group and 55.6±12.5% in the standard-care group (mean adjusted difference, 10.5 percentage points; 95% confidence interval [CI], 7.0 to 14.0; P<0.001). Results for the secondary outcomes were consistent with those of the primary outcome; participants in the closed-loop group spent less time in a hyperglycemic state than those in the standard-care group (difference, −10.2 percentage points; 95% CI, −13.8 to −6.6); had more overnight time in the target range (difference, 12.3 percentage points; 95% CI, 8.3 to 16.2), and had lower glycated hemoglobin levels (difference, −0.31 percentage points; 95% CI, −0.50 to −0.12). Little time was spent in a hypoglycemic state. No unanticipated safety problems associated with the use of closed-loop therapy during pregnancy occurred (6 instances of severe hypoglycemia, vs. 5 in the standard-care group; 1 instance of diabetic ketoacidosis in each group; and 12 device-related adverse events in the closed-loop group, 7 related to closed-loop therapy).ConclusionsHybrid closed-loop therapy significantly improved maternal glycemic control during pregnancy complicated by type 1 diabetes. (Funded by the Efficacy and Mechanism Evaluation Program; AiDAPT ISRCTN Registry number, ISRCTN56898625.)

Hybrid Closed Loop Therapy in Adults With Type 1 Diabetes and Above-Target HbA1c: A Real-World Observational Study.

We explored longitudinal changes associated with switching to hybrid closed loop (HCL) insulin delivery systems in adults with type 1 diabetes and elevated HbA1c levels despite the use of intermittently scanned continuous glucose monitoring (isCGM) and insulin pump therapy. We undertook a pragmatic, preplanned observational study of participants included in the National Health Service England closed loop pilot. Adults using isCGM and insulin pump across 31 diabetes centers in England with an HbA1c ≥8.5% who were willing to commence HCL therapy were included. Outcomes included change in HbA1c, sensor glucometrics, diabetes distress score, Gold score (hypoglycemia awareness), acute event rates, and user opinion of HCL. In total, 570 HCL users were included (median age 40 [IQR 29-50] years, 67% female, and 85% White). Mean baseline HbA1c was 9.4 ± 0.9% (78.9 ± 9.1 mmol/mol) with a median follow-up of 5.1 (IQR 3.9-6.6) months. Of 520 users continuing HCL at follow-up, mean adjusted HbA1c reduced by 1.7% (95% CI 1.5, 1.8; P < 0.0001) (18.1 mmol/mol [95% CI 16.6, 19.6]; P < 0.0001). Time in range (70-180 mg/dL) increased from 34.2 to 61.9% (P < 0.001). Individuals with HbA1c of ≤58 mmol/mol rose from 0 to 39.4% (P < 0.0001), and those achieving ≥70% glucose time in range and <4% time below range increased from 0.8 to 28.2% (P < 0.0001). Almost all participants rated HCL therapy as having a positive impact on quality of life (94.7% [540 of 570]). Use of HCL is associated with improvements in HbA1c, time in range, hypoglycemia, and diabetes-related distress and quality of life in people with type 1 diabetes in the real world.

108-LB: Randomized Trial of Automated Insulin Delivery in Pregnant Women with Type 1 Diabetes

Objective: To examine the clinical efficacy of automated insulin delivery (AID) during type 1 diabetes (T1D) pregnancy. Methods and Outcomes: We randomized pregnant women with T1D from nine UK clinical sites to hybrid closed-loop (CamAPS FX) or standard insulin therapy with continuous glucose monitoring. The primary outcome was the between-group difference in percentage time in the pregnancy-specific target glucose range (63-140mg/dl) from 16-weeks’ gestation until delivery. Analyses were performed according to intention-to-treat principles. Key secondary outcomes included overnight time-in-range (TIR), time spent hyperglycaemic (time-above-range, TAR &amp;gt;140mg/dl), HbA1c and safety events. Results: 124 participants (aged 31.1 ± 5.3yrs, HbA1c 7.7 ± 1.2%, T1D duration 2-31yrs, weight 49.0-138.0kg, total daily insulin doses 0.3-1.4units/kg) were randomized. The percentage of time that maternal glucose levels were within target was higher during AID than standard insulin therapy; mean between-group treatment difference 10%; 95% CI 7 to 10%; p &amp;lt; 0.001. Participants randomized to AID had larger reductions in hyperglycemia (AID vs control -11%; 95% CI -14 to - 7%; p&amp;lt;0.001), higher overnight time-in-range; (13%; 95% CI 9 to 17%; p&amp;lt;0.001), and lower HbA1c (-0.34%; 95%CI -0.52 to -0.15%; p&amp;lt;0.001), without additional insulin, weight gain or hypoglycemia. The treatment effect was apparent from early pregnancy, consistent across clinical sites, maternal HbA1c categories and previous insulin pump or injections. A significantly higher percent of AID participants reached CGM targets (TIR &amp;gt;70%: 46% vs 10%; p&amp;lt;0.001 and TAR &amp;lt;25%: 37% vs 11%; p=0.007 [AID vs. control]). One neonatal death that was unrelated to standard insulin therapy occurred. Conclusions: AID significantly improved maternal glycemia throughout T1D pregnancy. Our results support proposed NICE guideline recommendations that hybrid closed-loop therapy should be offered to all pregnant women with T1D. Disclosure H. R. Murphy: Advisory Panel; Medtronic, Research Support; Dexcom, Inc. L. Shepstone: None. M. E. Wilinska: Consultant; CamDiab Ltd. S. Bergford: None. J. Sibayan: None. C. Kollman: Research Support; Insulet Corporation, Dexcom, Inc., Tandem Diabetes Care, Inc. R. Beck: Consultant; Eli Lilly and Company, Novo Nordisk, Diasome, Insulet Corporation, Research Support; Tandem Diabetes Care, Inc., Beta Bionics, Inc., Dexcom, Inc., Bigfoot Biomedical, Inc., Medtronic, Ascensia Diabetes Care, Roche Diabetes Care, Eli Lilly and Company, Novo Nordisk. R. Hovorka: Advisory Panel; Ypsomed AG, Consultant; Abbott Diabetes, B. Braun, Speaker's Bureau; Eli Lilly and Company, Stock/Shareholder; CamDiab Ltd. T. T. M. Lee: None. C. Collett: None. S. Hartnell: Advisory Panel; Dexcom, Inc., Medtronic, Consultant; CamDiab Ltd., Other Relationship; AskDiabetes Ltd, Speaker's Bureau; Abbott Diabetes, Ypsomed AG. E. M. Scott: Research Support; Abbott Diabetes, Speaker's Bureau; Abbott Diabetes. R. S. Lindsay: None. K. F. Hunt: None. D. R. Mccance: None. M. Hammond: None. Funding National Institute for Health Research (16/35/01); JDRF (22-2013-266, 2-RSC-2019-828-M-N); Diabetes Research and Wellness Foundation (SECF/21 to T.T.M.L.)

273-OR: Hybrid Closed-Loop Therapy vs. Other Modalities of Therapy during Ramadan Intermittent Fasting in Adults and Adolescents with Type 1 Diabetes

Introduction: Most people with type 1 diabetes (PwT1D) are considered high risk to fast during the month of Ramadan. Yet, many of them attempt to fast and abstain from eating and drinking from dawn to dusk. Here, we evaluate the association between the sociodemographic indicators, modality of T1D treatment, and number of days when fasting is broken due to diabetes among PwT1D. Methods: We surveyed 294 PwT1D who attempted to fast during Ramadan 2022, were seen at our Endocrine clinics during the month preceding Ramadan, and who agreed to share their health information and fasting experience. Participants were categorized into 5 groups based on their treatment modality: a) Pump + CGM [Hybrid closed loop (HCL)] (n=62); b) Pump + CGM [Conventional open loop] (n=37); c) Pump + Self-monitoring of blood glucose (SMBG) (n=8); d) Multiple daily injections (MDI) + CGM (n=155); e) MDI + SMBG (n=32). Predictors for fasting most days of Ramadan (i.e. breaking fast ≤ 2 days) were analyzed using uni- and multi-variable logistic regression. Results: Private health insurance rates were highest among pump users (82%, 63%, and 41% for HCL, Pump + SMBG, and conventional open loop, respectively); whereas, MDI users had the lowest insurance rates (25% and 21% for MDI + SMBG and MDI + CGM, respectively). The median numbers of days when fasting was broken due to diabetes were 2, 5, 3, 3.5, and 2.5 days among the HCL, conventional open loop, MDI + CGM, Pump + SMBG, and MDI + SMBG groups, respectively (p=.047). Users of HCL therapy were two times as likely to complete fasting most days of Ramadan (i.e. breaking fast ≤2 days) compared to MDI + CGM users [odds ratio (95% CI): 2.37 (1.14, 4.90)] after adjusting for age, sex, educational level, employment status, insurance status, and diabetes duration. Conclusion: Among the common treatment modalities of T1D, the use of HCL pump therapy is associated with the highest rates of fasting most days of Ramadan after adjusting for potential confounders. Disclosure M.Al-sofiani: Consultant; Eli Lilly and Company, Speaker's Bureau; Sanofi, Medtronic, Vitalair. S.Alharthi: None. S.Albunyan: Employee; ProMedEx, Medtronic. N.Alzaman: None. D.C.Klonoff: Consultant; EOFlow Co., Ltd., Fractyl Health, Inc., Integrity, Lifecare, Inc., Rockley Photonics, Thirdwayv Inc. A.M.Alguwaihes: Consultant; Eli Lilly and Company, Research Support; AstraZeneca, Novo Nordisk, Speaker's Bureau; Novo Nordisk, Sanofi.