Real Time Continuous Glucose Monitoring System in T2DM With Pregnacy

Study Overview
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Brief Summary
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The prevalence of type 2 diabetes mellitus (T2DM) in women of childbearing age is increasing rapidly, and low glucose compliance leads to an increased risk of adverse pregnancy outcomes for mothers and infants during pregnancy in women with T2DM. Real-time continuous glucose monitoring (CGM) is an important tool for glucose monitoring and patient education, as it can continuously record blood glucose throughout the day and provide real-time feedback on high and low blood glucose levels. This is a multicenter, open-label, randomized controlled clinical study to investigate the efficacy, safety, and maternal and infant pregnancy outcomes of using real-time CGM monitoring compared with conventional self-monitoring of blood glucose (SMBG) on the basis of multidisciplinary management in pregnant women with T2DM. One hundred and twenty pregnant women with T2DM in early pregnancy who were enrolled in intensive insulin therapy were randomly divided into the real-time CGM group and the conventional SMBG group. The real-time CGM intervention group wore real-time CGM for more than 50% of the pregnancy in addition to regular SMBG; the control group only performed regular SMBG. Both groups wore Medtronic iPro 2 for 3 days in early, mid and late pregnancy, and the time in the target range of blood glucose (TIR) was recorded in a blinded manner. Primary outcome: differences in TIR between the two groups of pregnant women in early, mid, and late pregnancy. Secondary outcomes included differences in glycated hemoglobin, hypoglycemia, insulin dose before delivery, pregnancy weight gain, and maternal and infant pregnancy outcomes.

Official Title
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Effect of Real Time Continuous Glucose Monitoring System on Management of Women With Type 2 Diabetes Mellitus During Pregnancy in a Multidisciplinary Comprehensive System

Conditions
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Type2diabetes, Pregnancy Related, Continuous Glucose Monitoring, Time in Range, Pregnancy Outcome

Intervention / Treatment
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* Device: Real-time Continuous Glucose Monitoring System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A clear history of type 2 diabetes, or a history of type 2 diabetes diagnosed in early pregnancy Singleton gestation at 4-12 weeks, with substandard glycemic control (i.e., fasting glucose > 5.3 mmol/L, and or 1 hour postprandial glucose > 7.8 mmol/L, and or 2 hours postprandial glucose > 6.7 mmol/L) after lifestyle intervention ± basal insulin therapy, as assessed by the endocrinology department. Patients who need insulin regimen with basal plus meal or insulin pump regimen. Patients are willing and committed to establish and follow up in the obstetrics and gynecology departments of Peking University Third Hospital, Haidian District Hospital and Yanqing District Hospital during pregnancy, and are willing to provide information on obstetric examination and perinatal medical records if they are transferred to the hospital for special reasons for follow-up or delivery. Voluntarily participate in the study, examine and follow up according to this project and sign informed consent. Able to pass the screening period Adherence evaluation Exclusion Criteria: Patients with type 1 diabetes, specific type of diabetes or gestational diabetes Pregnancy with severe comorbidities or diabetic complications for which obstetrics does not recommend continuation of pregnancy, including but not limited to the following: proliferative retinopathy, chronic kidney disease (eGFR less than 60 mL/min/1.73± massive proteinuria), known coronary and cerebrovascular disease, autoimmune system disease and receiving exogenous glucocorticoids or immunosuppressive therapy. Patients who have been hospitalized for psychiatric treatment within 6 months prior to enrollment or are still on psychiatric medications. Patients who have received other interventional studies.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention group<br>The intervention group will wear real-time CGM (120 cases) to monitor blood glucose and is required to use real-time-CGM more than 50% of the time every 4 weeks, the more the better. | Device: Real-time Continuous Glucose Monitoring System<br>* The intervention group wore real-time CGM (120 cases) to monitor blood glucose, and was required to use real-time-CGM more than 50% of the time every 4 weeks, the more the better.<br>|
| No Intervention: Control group<br>The control group will be followed up with traditional SMBG (120 cases) monitoring. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The difference of Time in Range (TIR) | The iPro2 device was used to calculate TIR(the control range of blood glucose during pregnancy was 3.5-7.8mmol/L), and the average value of TIR obtained from two measurements was used as the main outcome index. | 24-28 weeks (second trimester), 34-38 weeks (2 weeks before delivery) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time Above Range(TAR） | The data were recorded via iPro2(the time above control range of blood glucose during pregnancy) | 24-28 weeks (second trimester), 34-38 weeks (2 weeks before delivery) | 
| Time Below Range(TBR) | The data were recorded via iPro2 (the time below control range of blood glucose during pregnancy) | 24-28 weeks (second trimester), 34-38 weeks (2 weeks before delivery) | 
| Mean Amplitude Of Glycemic Excursion(MAGE) | The data were recorded via iPro2. | 24-28 weeks (second trimester), 34-38 weeks (2 weeks before delivery) | 
| Coefficient of Variation (CV) | The data were recorded via iPro2. | 24-28 weeks (second trimester), 34-38 weeks (2 weeks before delivery) | 
| Standard difference (SD) | The data were recorded via iPro2. | 24-28 weeks (second trimester), 34-38 weeks (2 weeks before delivery) | 
| Mean absolute relative difference (MARD) | The data were recorded via iPro2. | 24-28 weeks (second trimester), 34-38 weeks (2 weeks before delivery) | 
| Interquartile range(IQR) | The data were recorded via iPro2. | 24-28 weeks (second trimester), 34-38 weeks (2 weeks before delivery) | 
| Interdencile range (IDR) | The data were recorded via iPro2. | 24-28 weeks (second trimester), 34-38 weeks (2 weeks before delivery) | 
| Patient-reported severe hypoglycemic events | Number of patient-reported severe hypoglycemic events (hypoglycemic events requiring assistance) from enrollment to 42 weeks of gestation. | From enrollment to 42 weeks gestation | 
| Patient-reported severe hypoglycemic events | (a) Number of patient-reported severe hypoglycemic events (hypoglycemic events requiring assistance) from enrollment to 42 weeks of gestation; (b) Number of mild hypoglycemic (<3.5 mmol/l) and moderate hypoglycemic (<2.8 mmol/L) events detected by patient self-monitoring from enrollment to 42 weeks of gestation (c) Area under the curve for mild hypoglycemia (<3.5 mmol/l) and moderate hypoglycemia (<2.8 mmol/L) at 24, 28 and 34 weeks of gestation as indicated by the ambulatory glucose monitoring device; (d) Area under the curve for mild hypoglycemia (<3.5 mmol/l) and moderate hypoglycemia (<2.8 mmol/L) at night (23:00-7:00) as indicated by the ambulatory glucose monitoring device at 24, 28 and 34 weeks of gestation. | From enrollment to 42 weeks gestation | 
| Number of moderate hypoglycemic events | Number of moderate hypoglycemic (<2.8 mmol/L) events detected by patient self-monitoring from enrollment to 42 weeks of gestation; Area under the curve for moderate hypoglycemia (<2.8 mmol/L) at 24, 28 and 34 weeks of gestation as indicated by the ambulatory glucose monitoring device; (d) Area under the curve for moderate hypoglycemia (<2.8 mmol/L) at night (23:00-7:00) as indicated by the ambulatory glucose monitoring device at 24, 28 and 34 weeks of gestation. | From enrollment to 42 weeks gestation | 
| Number of mild hypoglycemic events | Number of mild hypoglycemic (<3.5 mmol/l) events detected by patient self-monitoring from enrollment to 42 weeks of gestation (c) Area under the curve for mild hypoglycemia (<3.5 mmol/l) at 24, 28 and 34 weeks of gestation as indicated by the ambulatory glucose monitoring device; (d) Area under the curve for mild hypoglycemia (<3.5 mmol/l) at night (23:00-7:00) as indicated by the ambulatory glucose monitoring device at 24, 28 and 34 weeks of gestation. | From enrollment to 42 weeks gestation | 
| Total insulin | the whole day dose of insulin | At 4 weeks after enrollment, 24, 28, 34 weeks gestation and 6 weeks postpartum. | 
| Maternal weight gain | The absolute value of maternal weight gain during pregnancy | From enrollment to 42 weeks gestation | 
| Glycosylated hemoglobin | Glycosylated hemoglobin during delivery | During delivery | 
| Glycosylated albumin | Glycosylated albumin during delivery | During delivery | 
| Number of Patients with Adverse pregancy outcome | Includign gestational hypertension, preeclampsia/eclampsia, Cesarean section rate, puerperal infection. | 6 weeks postpartum. | 
| Number of Pregnancy loss | Including abortion (less than 28 weeks gestation), stillbirth and neonatal death. | From enrollment to 6 weeks postpartum. | 
| Apgar score | Apgar score at birth, range from 0-10, evaluated activity, pulse, grimace, appearance, respiration. Score 8 to 10 is classified as no asphyxia, 4 to 7 is mild asphyxia, 0 to 3 is severe asphyxia | During delivery | 
| Number of neonatal hypoglycemia | Intravenous glucose infusion is required. | 6 weeks postpartum. | 
| The length of a newborn is treated in the neonatal intensive care unit (NICU) | The length of a newborn is treated in the neonatal intensive care unit (NICU) | 6 weeks postpartum. | 
| Gestational age at birth | The incidence of preterm delivery (28-37 weeks gestation at birth), full-term delivery (37-42 weeks gestation at birth), and overdue delivery (more than 42 weeks gestation at birth). | During delivery | 
| Number of macrosomia or fetal growth restriction | Macrosomia (birth weight greater than 4000 g) or fetal growth restriction (birth weight less than 2500) | During delivery | 
| Number of newborns with neonatal birth injury, shoulder dystocia, neonatal jaundice, neonatal respiratory distress syndrome (RDS) | Including neonatal birth injury, shoulder dystocia, neonatal jaundice, neonatal respiratory distress syndrome (RDS). | From birth to discharge. |