Safety and efficacy of automated insulin delivery systems for pregnant patients with T1DM

July 16, 2021

Pregnancy in women with type 1 diabetes mellitus (T1DM) is associated with adverse maternal, fetal and neonatal outcomes. Adverse maternal outcomes include gestational hypertension, preeclampsia, eclampsia, preterm delivery and cesarean delivery. Adverse fetal and neonatal outcomes have included early pregnancy loss, stillbirth, congenital anomalies, fetal growth and fluid abnormalities, neonatal hypoglycemia, and neonatal intensive care unit admission.

Similar to the nonpregnant T1DM patient, a pregnant patient with T1DM experiences high glucose variability, including frequent hypoglycemia and hyperglycemia. Glycemic control during pregnancy in patients with T1DM continues to be suboptimal with significant time spent in hypoglycemia and hyperglycemic ranges.

For the nonpregnant patient with T1DM, management and treatment options have improved significantly since 2017, especially with the approval of automated insulin delivery systems. In addition, there are now several options available for continuous glucose monitoring. Unfortunately, testing and use of these technological advances, including continuous glucose monitoring devices and automated insulin delivery systems, have continued to be very limited for patients with T1DM during pregnancy.

Yogish C. Kudva, M.B.B.S., Endocrinology, Diabetes, Metabolism, and Nutrition, at Mayo Clinic in Rochester, Minnesota, says: "Testing of technologic advances including continuous glucose monitoring devices and automated insulin delivery systems during pregnancy has been limited in patients with T1DM. More recently, continuous glucose monitoring has been tested in a randomized, controlled trial and shown to be efficacious for some endpoints. However, no continuous glucose monitoring system is currently approved for use in pregnancy in the U.S. Automated insulin delivery system use during pregnancy has been tested, especially in the United Kingdom, with results published in Diabetes Care in 2018. Such testing in the U.S. has been limited to a single study, Pregnancy Intervention With a Closed-Loop System (PICLS) Study (PICLS), which involves an automated insulin delivery algorithm approved only in the nonpregnant state.

Safety and efficacy study at Mayo Clinic

Recently, Mayo Clinic's campus in Rochester, Minnesota, was selected as one of three clinical sites to perform studies of automated insulin delivery system use by pregnant people with T1DM in a supervised environment for 48 hours. Each clinical site has a multidisciplinary research team led by an endocrinologist working closely with the high-risk obstetrician.

Mari Charisse (Charisse) Trinidad, M.D., Obstetrics and Gynecology, at Mayo Clinic in Minnesota, says, "The automated insulin delivery system was developed by engineers at Harvard School of Engineering and specifically designed to address the unique glucose control requirements of pregnancy. This consortium is now approved to test the automated insulin delivery system at home — for consenting patients — after an initial 48-hour supervised environment study.

"The continuous glucose monitoring device will be worn on the patient's arm throughout the pregnancy. Initially, however, patients will need to test their glucose using a glucometer both before and two hours after each meal and at bedtime daily. Data from the continuous glucose monitor will be compared to self-monitoring of blood glucose data for accuracy, and when current standards are met, patients can proceed to use the continuous glucose monitor during the pregnancy for further automated insulin delivery."

The automated insulin delivery system consists of a Tandem insulin pump and an automated insulin delivery algorithm that is loaded on a Google phone. Glucose control also will be closely monitored by the research team.

Dr. Kudva notes: "The current study is a safety and efficacy study. Patients will be recruited between 14 to 32 weeks of pregnancy. Recruited patients can use the system for the rest of the pregnancy. Safety outcomes will be gathered for both mother and baby. In addition, efficacy outcomes will include glucose control metrics that are specific for pregnancy. Time in target during continuous glucose monitoring (CGM) will be measured; percentage time below 63 mg/dL, time in target 63 to 140 mg/dL, time >140 mg/dL, time >180 mg/dL and time > 250 mg/dL will be reported separately. In addition, percentage of time for which CGM is available and percentage of time for active closed loop will be reported."

Preliminary data suggests time in target increased from 60% during the run-in phase to 80% during the 48 hours of the study. Results from this research study were presented at the annual scientific sessions of the American Diabetes Association, June 25-27, 2021.

The current study aims to enroll 10 patients across three clinical sites. Enrollment is expected to be complete by December 2021; the study is expected to be complete by May 2022. Interested patients can contact the Mayo Clinic research team at 507-255-5916 for more information about the study and enrollment.

For more information

Stewart ZA, et al. Day-and-night closed-loop insulin delivery in a broad population of pregnant women with type 1 diabetes: A randomized controlled crossover trial. Diabetes Care. 2018;41:1391.

Pregnancy Intervention With a Closed-Loop System (PICLS) Study (PICLS).