Longitudinal Observation of Insulin Use and Glucose Sensor Metrics in Pregnant Women with Type 1 Diabetes Using Continuous Glucose Monitors and Insulin Pumps: The LOIS-P Study

O’Malley, Grenye; Özaslan, Başak; Levy, Carol J.; Castorino, Kristin; Desjardins, Donna; Levister, Camilla; McCrady-Spitzer, Shelly K.; Church, Mei Mei; Kaur, Ravinder; Reid, Corey; Kremers, Walter K.; Doyle, Francis J.; Trinidad, Mari Charisse; Rosenn, Barak; Pinsker, Jordan E.; Kudva, Yogish C.; Dassau, Eyal

doi:10.1089/dia.2021.0112

Cited by 22 publications

(8 citation statements)

References 29 publications

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“…Future individual patient data meta-analyses using data from AIDAPT and four ongoing studies of closed-loop (NCT0452097, NCT03774186, NCT04902378, NCT04492566) are planned to examine the effects on rarer pregnancy outcomes such as severe hypoglycaemia and diabetic ketoacidosis events. This may also be able to examine differences between different hybrid closed-loop systems, including commercially available systems and pregnancy-specific automated insulin delivery [ 10 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

AiDAPT: automated insulin delivery amongst pregnant women with type 1 diabetes: a multicentre randomized controlled trial – study protocol

Lee

Hartnell

Barnard‐Kelly

et al. 2022

BMC Pregnancy Childbirth

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Background Pregnant women with type 1 diabetes strive for tight glucose targets (3.5-7.8 mmol/L) to minimise the risks of obstetric and neonatal complications. Despite using diabetes technologies including continuous glucose monitoring (CGM), insulin pumps and contemporary insulin analogues, most women struggle to achieve and maintain the recommended pregnancy glucose targets. This study aims to evaluate whether the use of automated closed-loop insulin delivery improves antenatal glucose levels in pregnant women with type 1 diabetes. Methods/design A multicentre, open label, randomized, controlled trial of pregnant women with type 1 diabetes and a HbA1c of ≥48 mmol/mol (6.5%) at pregnancy confirmation and ≤ 86 mmol/mol (10%) at randomization. Participants who provide written informed consent before 13 weeks 6 days gestation will be entered into a run-in phase to collect 96 h (24 h overnight) of CGM glucose values. Eligible participants will be randomized on a 1:1 basis to CGM (Dexcom G6) with usual insulin delivery (control) or closed-loop (intervention). The closed-loop system includes a model predictive control algorithm (CamAPS FX application), hosted on an android smartphone that communicates wirelessly with the insulin pump (Dana Diabecare RS) and CGM transmitter. Research visits and device training will be provided virtually or face-to-face in conjunction with 4-weekly antenatal clinic visits where possible. Randomization will stratify for clinic site. One hundred twenty-four participants will be recruited. This takes into account 10% attrition and 10% who experience miscarriage or pregnancy loss. Analyses will be performed according to intention to treat. The primary analysis will evaluate the change in the time spent in the target glucose range (3.5-7.8 mmol/l) between the intervention and control group from 16 weeks gestation until delivery. Secondary outcomes include overnight time in target, time above target (> 7.8 mmol/l), standard CGM metrics, HbA1c and psychosocial functioning and health economic measures. Safety outcomes include the number and severity of ketoacidosis, severe hypoglycaemia and adverse device events. Discussion This will be the largest randomized controlled trial to evaluate the impact of closed-loop insulin delivery during type 1 diabetes pregnancy. Trial registration ISRCTN 56898625 Registration Date: 10 April, 2018.

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Section: Discussionmentioning

confidence: 99%

AiDAPT: automated insulin delivery amongst pregnant women with type 1 diabetes: a multicentre randomized controlled trial – study protocol

Lee

Hartnell

Barnard‐Kelly

et al. 2022

BMC Pregnancy Childbirth

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“…In this scenario, we test the controller performance in a setting similar to the end of pregnancy by introducing a 67% decrease in the parameters k p 3 and V mx to induce insulin resistance ( 34 ). The treatment parameters are adjusted in accordance with the existing literature that show that the basal profile increases by 50% ( 35 , 36 ), while the prescribed CR is decreased by 50% ( 37 ) and CF is decreased by 33% ( 38 ) relative to the treatment parameters in early pregnancy. In this setup, we run simulations under the following conditions:…”

Section: Methodsmentioning

confidence: 99%

Zone-MPC Automated Insulin Delivery Algorithm Tuned for Pregnancy Complicated by Type 1 Diabetes

et al. 2022

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Type 1 diabetes (T1D) increases the risk for pregnancy complications. Increased time in the pregnancy glucose target range (63-140 mg/dL as suggested by clinical guidelines) is associated with improved pregnancy outcomes that underscores the need for tight glycemic control. While closed-loop control is highly effective in regulating blood glucose levels in individuals with T1D, its use during pregnancy requires adjustments to meet the tight glycemic control and changing insulin requirements with advancing gestation. In this paper, we tailor a zone model predictive controller (zone-MPC), an optimization-based control strategy that uses model predictions, for use during pregnancy and verify its robustness in-silico through a broad range of scenarios. We customize the existing zone-MPC to satisfy pregnancy-specific glucose control objectives by having (i) lower target glycemic zones (i.e., 80-110 mg/dL daytime and 80-100 mg/dL overnight), (ii) more assertive correction bolus for hyperglycemia, and (iii) a control strategy that results in more aggressive postprandial insulin delivery to keep glucose within the target zone. The emphasis is on leveraging the flexible design of zone-MPC to obtain a controller that satisfies glycemic outcomes recommended for pregnancy based on clinical insight. To verify this pregnancy-specific zone-MPC design, we use the UVA/Padova simulator and conduct in-silico experiments on 10 subjects over 13 scenarios ranging from scenarios with ideal metabolic and treatment parameters for pregnancy to extreme scenarios with such parameters that are highly deviant from the ideal. All scenarios had three meals per day and each meal had 40 grams of carbohydrates. Across 13 scenarios, pregnancy-specific zone-MPC led to a 10.3 ± 5.3% increase in the time in pregnancy target range (baseline zone-MPC: 70.6 ± 15.0%, pregnancy-specific zone-MPC: 80.8 ± 11.3%, p < 0.001) and a 10.7 ± 4.8% reduction in the time above the target range (baseline zone-MPC: 29.0 ± 15.4%, pregnancy-specific zone-MPC: 18.3 ± 12.0, p < 0.001). There was no significant difference in the time below range between the controllers (baseline zone-MPC: 0.5 ± 1.2%, pregnancy-specific zone-MPC: 3.5 ± 1.9%, p = 0.1). The extensive simulation results show improved performance in the pregnancy target range with pregnancy-specific zone MPC, suggest robustness of the zone-MPC in tight glucose control scenarios, and emphasize the need for customized glucose control systems for pregnancy.

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“…Their experiences are similar to those reported in subsequent studies of CGM use performed in Europe and the USA. 14,18 Furthermore, problems encountered by CGM users were common. Over 80% of CONCEPTT trial participants reported frustrations including irritations with frequent CGM alarms, connectivity issues and sensor accuracy.…”

Section: Fundingmentioning

confidence: 99%

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

Lee,

Collett,

Bergford

et al. 2024

Efficacy Mech Eval

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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 (> 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 < 0.001). Results were consistent in secondary outcomes, with less time above range (−10.2%, 95% confidence interval −13.8 to −6.6%; p < 0.001), higher overnight time in range (12.3%, 95% confidence interval 8.3 to 16.2%; p < 0.001) and lower glycated haemoglobin A1c (−0.31%, 95% confidence interval −0.50 to −0.12%; p < 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.

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Longitudinal Observation of Insulin Use and Glucose Sensor Metrics in Pregnant Women with Type 1 Diabetes Using Continuous Glucose Monitors and Insulin Pumps: The LOIS-P Study

Cited by 22 publications

References 29 publications

AiDAPT: automated insulin delivery amongst pregnant women with type 1 diabetes: a multicentre randomized controlled trial – study protocol

AiDAPT: automated insulin delivery amongst pregnant women with type 1 diabetes: a multicentre randomized controlled trial – study protocol

Zone-MPC Automated Insulin Delivery Algorithm Tuned for Pregnancy Complicated by Type 1 Diabetes

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

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