Automated Insulin Delivery in Women with Pregnancy Complicated by Type 1 Diabetes. AiDAPT triaN Engl J Med Oct 5
Hybrid closed-loop insulin therapy has shown promise for management of type 1 diabetes during pregnancy; however, its efficacy is unclear.
In 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 ac-ording to the intention-to-treat principle. Key secondary outcomes were the per-centage 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
A 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)
Hybrid closed-loop therapy significantly improved maternal glycemic control during pregnancy complicated by type 1 diabetes.
Editorial in summary
In addition, major barriers exist to implementing use of a closed-loop system or continuous glucose monitoring, including biases related to socioeconomic status, ethnicity, and implicit racial bias.
Clearly, closed-loop systems have changed the landscape of diabetes care in nonpregnant populations. Although more studies are needed, the AiDAPT trial provides hope that this landscape may also be altered for the better for pregnant persons with type 1 diabetes.
From the article
However, despite advancements in insulin therapy, continuous glucose monitoring, and high motivation among pregnant persons to manage their diabetes, most pregnant persons with diabetes do not have glucose levels in the pregnancy-specific glucose target range of 63 to 140 mg per deciliter (3.5 to 7.8 mmol per liter), which is lower than the target range of 70 to 180 mg per deciliter (3.9 to 10.0 mmol per liter) for nonpreg-nant persons.
The use of hybrid closed-loop therapy is associated with improved glucose control in non-pregnant adults and in children, but whether the more stringent glucose targets required for optimal pregnancy outcomes can be achieved with this therapy is unknown.
The CamAPS FX is a hybrid closed-loop system that enables automatically adjusted insulin delivery from an insulin pump according to real-time glucose-sensor measurements. This system was approved for use during pregnancy in the United Kingdom on the basis of results from two feasibility stud-ies.
Subsequently, the system was updated, leading to two key changes: first, glucose measurements from continuous glucose monitors can now be used to inform user-initiated pre-meal boluses of insulin; second, additional features allow the user to intensify or relax closed-loop insulin delivery and to specify personalized glucose targets, which the user can adjust dur-ing pregnancy.
We tested whether hybrid closed-loop therapy initiated before 16 weeks’ gestation would improve maternal glucose levels during pregnancy complicated by type 1 diabetes.
We found that the percentage of time that glucose levels were within the pregnancy-specific target range of 63 to 140 mg per deciliter from 16 weeks’ gestation until delivery was 10.5 percents points higher, an additional 2.5 hours per day, among participants assigned to closed-loop therapy than among those assigned to continuous glucose monitoring alongside their usual insulin-delivery method.
The time-in-range benefits were achieved by a reduction in maternal hyperglycemia and an increase in nocturnal time in the target range. Improvements in glucose outcomes were consistent across baseline maternal age, glycated hemoglobin levels, clinical sites, and pretrial insulin-delivery method. Furthermore, there was no increase in gestational weight gain or maternal insulin doses with closed-loop therapy.
The incidence of hypoglycemia was low at baseline, and apart from a lower incidence of nighttime hypoglycemia events in the closed-loop group than in the standard-care group, did not differ between groups.
Among patients receiving closed-loop therapy, an increase of 5 percentage points in the time in the target range was apparent by the end of the first trimester, which suggests that the benefits occurred soon after initiation of closed-loop therapy (which occurred at approxi-mately 12 weeks’ gestation); this time frame is crucially important for women and clinicians considering therapeutic changes during early pregnancy.
The trial was conducted during the Covid-19 pandemic, which particularly affected pregnant persons, and necessitated rapid implementation of virtual training and visits. Nonetheless, use of the closed-loop system was high (>95%) through-out pregnancy and without apparent safety prob-lems, including among participants who were new to insulin-pump therapy.
Participants who continued standard care had more clinic visits and more unscheduled contacts, which suggests that beyond initial training, use of the closed-loop system did not require additional input from health care professionals.
Recent trials have shown the benefits of closed-loop therapy in persons with newly diagnosed type 1 diabetes and young children, and these results extend the evidence to pregnant women.
Alongside the participants’ motivation to minimize pregnancy complications, closed-loop therapy facilitated attainment of glucose levels in the pregnancy-specific target range 70% of the time.
Given the rapid increase in the time in the target range observed within 1 week after initiation of therapy in this trial, and within 1 day in a recent trial,we speculate that further benefits may be obtained from starting closed-loop therapy before pregnancy or as soon as possible after pregnancy is confirmed.
Participants were offered the option to continue closed-loop therapy during the inpatient admission for labor and delivery (results not reported here).
The participants in the current trial gained an additional 10 percentage points of time in the target range above the 10 percentage-point increment seen with continuous glucose monitor-ing and standard insulin therapy during preg-nancy. Previous studies have shown that every increase of 5 percentage points of the time in the target range is associated with improved obstetrical and neonatal outcomes.
Our trial was not powered for pregnancy outcomes, but we infer that this additional 10 percentage points of time in the pregnancy-specific target range would be expected to have additional health benefits for pregnant persons and their babies.
Strengths of our trial include its randomized, controlled design; the generalizability of our population, which included participants who had not previously received insulin-pump therapy; a large percentage of participants who initiated therapy during the first trimester; and a flexible trial protocol that facilitated virtual or in-person visits.
We observed no increase in clinical contacts, which is often observed in trials of investigational devices.
This trial had certain limitations. The sample size did not provide definitive data on maternal and neonatal health outcomes. Most of the participants (93%) were white, participants were excluded if they did not have a glycated hemoglobin level of 10% or less by the time of randomization, and 56% of the participants had an undergraduate or equivalent education.
First-trimester data were limited because participants underwent randomization at a median of 11 weeks’ gestation. We did not record the use of the CamAPS Boost and Ease-Off features of the closed-loop system, and data cannot be extrapolated to systems with higher glucose-level targets.In this trial, closed-loop therapy was effective during pregnancy complicated by type 1 diabetes, accounting for the marked gestational changes in insulin doses in trial participants, and pro-vided a clinical advantage beyond that achieved with continuous glucose monitoring and insu-lin-pump therapy.
These results support the in Pregnancy recommendations, proposed in the guideline from the National Institute for Health Care Excellence (NICE), that hybrid closed-loop therapy should be offered to all pregnant persons with type 1 diabetes.
På amerikanska diabetesmötet ADA presenterades studien i juni så som en stor highlight i form av e-poster. Helen B Murphy presenterade dessa data. ”Start automatic insulin pump therapy as early as possible in patients with pregnant women with T1DM.”
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