Continuous Glucose Monitoring in Women With Type 1 Diabetes in Pregnancy Trial

In women with diabetes, hyperglycemia is associated with increased rates of numerous
maternal and fetal adverse outcomes. Mothers are at increased risk of preeclampsia,
polyhydramnios, and caesarean sections. Infants of mothers with diabetes have increased
rates of congenital anomalies, premature delivery, macrosomia, stillbirth and NICU
admissions. Macrosomia itself is associated with numerous adverse fetal outcomes including
shoulder dystocia, birth injury, neonatal hypoglycemia, hyperbilirubinemia, respiratory
distress syndrome and NICU admissions, asphyxia and death. Postprandial blood sugars in
particular have been associated with increased macrosomia rates.

Numerous studies have shown that pregnancy outcomes can be reduced with improved glycemic
control. In particular, pre-pregnancy care has been shown to assist women improve glucose
control during the crucial period of organogenesis, and is associated with reduced rates of
adverse pregnancy outcome including major congenital malformation, stillbirth and neonatal
death.

Technological advances aimed at reducing glycemic excursions and improving glucose control
in patients with diabetes include the continuous glucose monitoring (CGM) system. We
hypothesize that real-time CGM will assist women with type 1 diabetes to improve their
glycemic control before and during pregnancy.

Inclusion Criteria:

- Clinical diagnosis of type 1 diabetes and using daily insulin therapy for at least
one year

- Age 18-40 years

- Insulin regimen involves either the use of an insulin pump or multiple daily
injections of insulin (at least 3 shots per day). Subjects using premixed fixed doses
of insulin at the time of enrolment will not be eligible. Insulin regimen must be
stable for at least 4 weeks (i.e. on multiple insulin injections or on insulin pump)
prior to randomization.

- No expectation that subject will be moving out of the area of the clinical center
during the next year, unless the move will be to an area served by another study
center

- Informed Consent Form signed by the subject

In addition, specific eligibility criteria apply to the respective groups:

Pre-pregnancy Group:

- Patients who are planning pregnancy and wish to optimise glycemic control before
conception

Pregnancy Group:

- Pregnancy gestation ≤13 weeks, 6 days at time of randomization

- Live singleton fetus

- Dating ultrasound (US) done to confirm gestational age, viability and rule out
multiples. Gestational age will be based on the last menstrual period (LMP) provided
there is a ≤5 day discrepancy with US dates in the first trimester and ≤10 day
discrepancy with US dates in the second trimester. If the dates from LMP are outside
these limits, the US dates will be used as the best estimate of gestational age.

Exclusion Criteria:

- Type 2 diabetes

- Gestational diabetes

- Previous participation in the study

- Estimated GFR <60 ml/min/1.73

- The presence of a significant medical disorder or use of a medication such as oral
glucocorticoids that in the judgment of the investigator will affect the wearing of
the sensors or the completion of any aspect of the protocol.

If the investigator is uncertain whether the patient would be eligible; i.e. if the
medical disorder would constitute an exclusion, the Steering Committee will be asked to
make the decision.

- Inpatient psychiatric treatment in the past 6 months

- Subjects using premixed fixed doses of insulin at the time of enrolment

In addition, specific exclusion criteria apply to the respective groups:

Pre-pregnancy Group:

- HbA1c <7.0% or >10.0%

Pregnancy Group:

- HbA1c <6.5% or >10.0%

- Known current higher order pregnancies (twins, triplets, etc.) These women will be
excluded as they have a higher rate of adverse outcomes and could lead to
inequalities if they are unequally distributed between the groups.

- Known potentially major fetal anomaly (as per EUROCAT criteria).