Diabetes Mellitus, Type 2
Conditions
Keywords
Pregnancy
Brief summary
To determine whether use of detemir compared to neutral protamine hagedorn (NPH) decreases rates of composite neonatal outcome and maternal hypoglycemia events in women with Type 2 Diabetes Mellitus (T2DM).
Interventions
DRUGNeutral Protamine Hagedorn (NPH)
NPH will peak between 4-12 hours after injection with a duration of action around 14 hours
DRUGDetemir insulin
Detemir is characterized by a gentle rise and fall with a longer duration of action (18-20 hours)
Sponsors
The University of Texas Health Science Center, Houston
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Preexisting type 2 diabetes mellitus requiring medical treatment or * overt diabetes diagnosed prior to 20 weeks of gestation using either Hemoglobin A1c (HBA1C) ≥ 6.5 or fasting glucose ≥126 mg/dl or random blood glucose ≥ 200 mg/dl or two step method ( 50g glucose challenge test (GCT) \>135 mg/dl followed by 100 GCT with at least 2 values above thresholds: Fasting Blood Glucose (FBG) \>90, 1 hr \>180, 2 hr \> 155, 3 hr \> 140 mg/dl). * Gestational age ≤20 weeks * Willing to start insulin therapy or to continue insulin treatment during pregnancy * Singleton or twin pregnancy
Exclusion criteria
* Known allergy/prior adverse reaction to NPH/detemir * Patients \<18y * Known major fetal anomalies * Diabetic nephropathy (Creatinine (Cr)≥1.5) * Diabetic proliferative retinopathy * Patients with Type 1 diabetes or gestational diabetes
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Neonates With Composite Adverse Neonatal Outcome | From the time of delivery to the time of discharge (about 2-14 days) | Composite Adverse Neonatal Outcome includes 1 or more of any of the following: * Neonatal intensive care unit (NICU) admission or * Neonatal hypoglycemia (\<40 mg/dL in the first 24 hours of life and less than 50 mg/dL after) or requiring medical therapy or * Respiratory distress (need for at least 4 hours of respiratory support with supplemental oxygen, continuous positive airway pressure or ventilation at the first 24 hours of life or * Shoulder dystocia - defined as the need for any extra maneuvers, other than gentle downward traction of the fetal head in order to deliver the fetal body after the fetal head has been delivered or * Large for gestational age (LGA) -weight over 90th percentile of the expected value according to gestational age or * Macrosomia- Fetal weight above 4000g |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maternal Mean Post Prandial Glucose | perinatal to postpartum (32 weeks) | — |
| Number of Maternal Subjects Who Experienced Hypoglycemic Events (<60 mg/dL) During Pregnancy | perinatal to postpartum (32 weeks) | — |
| Change in Maternal Weight During Pregnancy | perinatal to postpartum (32 weeks) | — |
| Number of Maternal Subjects Who Had Hypertensive Disorder During Pregnancy | perinatal to postpartum (32 weeks) | Hypertensive disorder includes gestational hypertension, preeclampsia, or superimposed preeclampsia. |
| Number of Maternal Subjects Who Had Preeclampsia With Severe Features | perinatal to postpartum (32 weeks) | — |
| Number of Subjects Who Had Cesarean Delivery | at delivery | — |
| Maternal Mean Fasting Glucose | perinatal to postpartum (32 weeks) | — |
| Gestational Weeks at Delivery | at delivery | — |
| Number of Neonates Who Where Small for Gestational Age (SGA) | at delivery | Small for gestational age (SGA) means that a fetus or an infant is smaller or less developed than normal for the baby's sex and gestational age. Small for gestational age (SGA) is defined as a birth weight that is below the 10th percentile. |
| Neonatal Hospital Admission Days | From the time of delivery to the time of discharge (about 2-14 days) | — |
| # of Neonates Who Had 5-minute Apgar Score < 7 | 5 minutes after delivery | The Apgar score is determined by evaluating the newborn baby on each of five criteria (appearance, pulse, grimace, activity, respiration) on a scale from zero to two, then summing the five values obtained. The total score ranges from zero to 10. A higher score indicates a better outcome. |
| Number of Neonates Who Had Jaundice Requiring Therapy | From the time of delivery to the time of discharge (about 2-14 days) | — |
| Number of Subjects Who Had Operative Vaginal Delivery | at delivery | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Detemir Detemir insulin: Detemir is characterized by a gentle rise and fall with a longer duration of action (18-20 hours) | 57 |
| Neutral Protamine Hagedorn (NPH) Neutral Protamine Hagedorn (NPH): NPH will peak between 4-12 hours after injection with a duration of action around 14 hours | 51 |
| Total | 108 |
Baseline characteristics
| Characteristic | Detemir | Neutral Protamine Hagedorn (NPH) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 57 Participants | 51 Participants | 108 Participants |
| Age, Continuous | 32.1 years STANDARD_DEVIATION 6.2 | 32.5 years STANDARD_DEVIATION 6 | 32.3 years STANDARD_DEVIATION 6.1 |
| Number of maternal participants who had private insurance for prenatal care | 22 Participants | 18 Participants | 40 Participants |
| Number of maternal participants who smoked during pregnancy | 2 Participants | 0 Participants | 2 Participants |
| Number of maternal participants who used alcohol during pregnancy | 2 Participants | 0 Participants | 2 Participants |
| Number of maternal participants who used aspirin during pregnancy | 27 Participants | 29 Participants | 56 Participants |
| Number of maternal participants who used rapid- or short-acting insulin | 38 Participants | 41 Participants | 79 Participants |
| Number of maternal participants who used substances during pregnancy | 3 Participants | 1 Participants | 4 Participants |
| Number of maternal participants who were nulliparous | 5 Participants | 7 Participants | 12 Participants |
| Number of maternal participants with body mass index (BMI) greater than 30 | 51 Participants | 38 Participants | 89 Participants |
| Number of maternal participants with chronic hypertension | 12 Participants | 17 Participants | 29 Participants |
| Number of maternal participants with depression or anxiety | 7 Participants | 9 Participants | 16 Participants |
| Number of maternal participants with diabetes mellitus diagnosed before pregnancy | 44 Participants | 42 Participants | 86 Participants |
| Number of maternal participants with HbA1c level greater than 6.5% | 37 Participants | 34 Participants | 71 Participants |
| Number of maternal participants with thyroid disease | 2 Participants | 4 Participants | 6 Participants |
| Race/Ethnicity, Customized Asian | 4 Participants | 0 Participants | 4 Participants |
| Race/Ethnicity, Customized Hispanic | 36 Participants | 31 Participants | 67 Participants |
| Race/Ethnicity, Customized Non-Hispanic Black | 14 Participants | 14 Participants | 28 Participants |
| Race/Ethnicity, Customized Non-Hispanic White | 3 Participants | 6 Participants | 9 Participants |
| Region of Enrollment United States | 57 Participants | 51 Participants | 108 Participants |
| Sex: Female, Male Female | 57 Participants | 51 Participants | 108 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 4 / 57 | 1 / 51 |
| other Total, other adverse events | 0 / 53 | 0 / 50 |
| serious Total, serious adverse events | 16 / 57 | 10 / 51 |
Outcome results
Primary
Number of Neonates With Composite Adverse Neonatal Outcome
Composite Adverse Neonatal Outcome includes 1 or more of any of the following: * Neonatal intensive care unit (NICU) admission or * Neonatal hypoglycemia (\<40 mg/dL in the first 24 hours of life and less than 50 mg/dL after) or requiring medical therapy or * Respiratory distress (need for at least 4 hours of respiratory support with supplemental oxygen, continuous positive airway pressure or ventilation at the first 24 hours of life or * Shoulder dystocia - defined as the need for any extra maneuvers, other than gentle downward traction of the fetal head in order to deliver the fetal body after the fetal head has been delivered or * Large for gestational age (LGA) -weight over 90th percentile of the expected value according to gestational age or * Macrosomia- Fetal weight above 4000g
Time frame: From the time of delivery to the time of discharge (about 2-14 days)
Population: All participants had singleton pregnancies (that is, there were no twins).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Detemir | Number of Neonates With Composite Adverse Neonatal Outcome | 31 Participants |
| Neutral Protamine Hagedorn (NPH) | Number of Neonates With Composite Adverse Neonatal Outcome | 35 Participants |
Secondary
Change in Maternal Weight During Pregnancy
Time frame: perinatal to postpartum (32 weeks)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Detemir | Change in Maternal Weight During Pregnancy | 7.00 kilograms (kg) |
| Neutral Protamine Hagedorn (NPH) | Change in Maternal Weight During Pregnancy | 9.00 kilograms (kg) |
Secondary
Gestational Weeks at Delivery
Time frame: at delivery
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Detemir | Gestational Weeks at Delivery | 37.10 weeks |
| Neutral Protamine Hagedorn (NPH) | Gestational Weeks at Delivery | 37.00 weeks |
Secondary
Maternal Mean Fasting Glucose
Time frame: perinatal to postpartum (32 weeks)
Population: Data were not collected for this outcome measure.
Secondary
Maternal Mean Post Prandial Glucose
Time frame: perinatal to postpartum (32 weeks)
Population: Data were not collected for this outcome measure.
Secondary
Neonatal Hospital Admission Days
Time frame: From the time of delivery to the time of discharge (about 2-14 days)
Population: All participants had singleton pregnancies (that is, there were no twins).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Detemir | Neonatal Hospital Admission Days | 4.0 days |
| Neutral Protamine Hagedorn (NPH) | Neonatal Hospital Admission Days | 4.1 days |
Secondary
Number of Maternal Subjects Who Experienced Hypoglycemic Events (<60 mg/dL) During Pregnancy
Time frame: perinatal to postpartum (32 weeks)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Detemir | Number of Maternal Subjects Who Experienced Hypoglycemic Events (<60 mg/dL) During Pregnancy | 8 Participants |
| Neutral Protamine Hagedorn (NPH) | Number of Maternal Subjects Who Experienced Hypoglycemic Events (<60 mg/dL) During Pregnancy | 16 Participants |
Secondary
Number of Maternal Subjects Who Had Hypertensive Disorder During Pregnancy
Hypertensive disorder includes gestational hypertension, preeclampsia, or superimposed preeclampsia.
Time frame: perinatal to postpartum (32 weeks)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Detemir | Number of Maternal Subjects Who Had Hypertensive Disorder During Pregnancy | 22 Participants |
| Neutral Protamine Hagedorn (NPH) | Number of Maternal Subjects Who Had Hypertensive Disorder During Pregnancy | 27 Participants |
Secondary
Number of Maternal Subjects Who Had Preeclampsia With Severe Features
Time frame: perinatal to postpartum (32 weeks)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Detemir | Number of Maternal Subjects Who Had Preeclampsia With Severe Features | 12 Participants |
| Neutral Protamine Hagedorn (NPH) | Number of Maternal Subjects Who Had Preeclampsia With Severe Features | 16 Participants |
Secondary
Number of Neonates Who Had Jaundice Requiring Therapy
Time frame: From the time of delivery to the time of discharge (about 2-14 days)
Population: All participants had singleton pregnancies (that is, there were no twins).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Detemir | Number of Neonates Who Had Jaundice Requiring Therapy | 15 Participants |
| Neutral Protamine Hagedorn (NPH) | Number of Neonates Who Had Jaundice Requiring Therapy | 11 Participants |
Secondary
Number of Neonates Who Where Small for Gestational Age (SGA)
Small for gestational age (SGA) means that a fetus or an infant is smaller or less developed than normal for the baby's sex and gestational age. Small for gestational age (SGA) is defined as a birth weight that is below the 10th percentile.
Time frame: at delivery
Population: All participants had singleton pregnancies (that is, there were no twins).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Detemir | Number of Neonates Who Where Small for Gestational Age (SGA) | 4 Participants |
| Neutral Protamine Hagedorn (NPH) | Number of Neonates Who Where Small for Gestational Age (SGA) | 6 Participants |
Secondary
Number of Subjects Who Had Cesarean Delivery
Time frame: at delivery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Detemir | Number of Subjects Who Had Cesarean Delivery | 32 Participants |
| Neutral Protamine Hagedorn (NPH) | Number of Subjects Who Had Cesarean Delivery | 30 Participants |
Secondary
Number of Subjects Who Had Operative Vaginal Delivery
Time frame: at delivery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Detemir | Number of Subjects Who Had Operative Vaginal Delivery | 1 Participants |
| Neutral Protamine Hagedorn (NPH) | Number of Subjects Who Had Operative Vaginal Delivery | 0 Participants |
Secondary
# of Neonates Who Had 5-minute Apgar Score < 7
The Apgar score is determined by evaluating the newborn baby on each of five criteria (appearance, pulse, grimace, activity, respiration) on a scale from zero to two, then summing the five values obtained. The total score ranges from zero to 10. A higher score indicates a better outcome.
Time frame: 5 minutes after delivery
Population: All participants had singleton pregnancies (that is, there were no twins).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Detemir | # of Neonates Who Had 5-minute Apgar Score < 7 | 3 Participants |
| Neutral Protamine Hagedorn (NPH) | # of Neonates Who Had 5-minute Apgar Score < 7 | 2 Participants |