Diabetes, Gestational, Diabetes, Type 2
Conditions
Keywords
Insulin, Long-Acting
Brief summary
The aim of this study is to compare glycemic control in pregnant women treated with insulin Detemir and pregnant women treated with NPH insulin. These women are diagnosed with gestational diabetes (GDM) in the current pregnancy or have a preexisting diagnosis of type 2 diabetes (T2DM) at the onset of pregnancy. Our hypothesis is that there is no difference between these two treatment modalities in terms of glycemic control in diabetes.
Detailed description
The experimental method will be a randomized controlled trial performed at Roosevelt Hospital in our Diabetes in Pregnancy Program (DIPP). Perinatologists managing the patient in DIPP determine when patients need further treatment with medical therapy. Patients undergoing care at DIPP may require medical intervention in the following clinical scenarios: failure of diet alone to control glycemic indices and grossly abnormal glucose tolerance screening test results suggesting disease of such severity that diet alone would not be sufficient. After verbally counseling the patient, she will be recruited for the study by the investigators. An extensive explanation of the objectives of the study will be presented to the patient, as well as written copies of the protocol and consent. After informed consent is given, patients will be randomized to management with either insulin NPH or detemir together with rapid acting insulin aspart (Novolog) with meals, as necessary. The primary outcome will be level of glycemic control defined as overall mean blood glucose in pregnancy. This is a well established measure of overall glycemic control that has been used in numerous publications in the obstetric literature on diabetes in pregnancy. Participants will be followed until they deliver, with an expected range of 6-16 weeks depending on when the patient was enrolled in the study. The mean glucose will be determined by the sum of average glucose at each visit divided by the number of visits).
Interventions
DRUGInsulin
Sponsors
St. Luke's-Roosevelt Hospital Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* All pregnant women with a viable singleton or multiple gestation at ≤34 weeks with gestational diabetes diagnosed in their current pregnancy requiring medical therapy. Early diagnosis GDM patients will also be included; which is defined as a diagnosis made prior to 24 weeks. * Women with known preexisting type 2 diabetes that are in need of medical therapy.
Exclusion criteria
* Patients \<18 years of age * a diagnosis of GDM outside of the gestational age stated above * known allergy/prior adverse reaction to insulin NPH or insulin detemir. * type 1 diabetes
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Glycemic Control | up to 41 weeks | Overall mean glucose value of pregnancy. This will be determined by the sum of average glucose value at each visit, divided by the number of visits. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Achieve Glycemic Control | up to 41 weeks | Time (weeks) to achieve glycemic control, as defined as mean glucose \<100mg/dl |
| Average Fasting Glucose | up to 41 weeks | Mean fasting blood glucose in pregnancy, as determined by the sum of the mean fasting glucose at each visit divided by the number of visits |
| Post-prandial Blood Glucose | up to 41 weeks | Mean post-prandial blood glucose in pregnancy, as defined as the sum of the average post-prandial blood glucose at each visit divided by the number of visits. |
| Weight Gain | Number of pounds gained at each visit up to 41 weeks | Total weight gain in pregnancy |
| Neonatal Weight | At delivery, up to 41 weeks | Neonatal weight was estimated for occurrence of neonatal macrosomia (≥4000g birth weight) and neonatal LGA(large for gestational age)(birth weight \>90th percentile for gestational age |
| Gestational Age at Delivery | at delivery, up to 41 weeks | Gestational age at delivery |
| Maternal Hypoglycemia | at delivery, up to 41 weeks | Number of participants with incidence of maternal hypoglycemia (\<60mg/dl) |
| Number of Patients Obtaining Glycemic Control | up to 41 weeks | Number of each group that obtains glycemic control, defined as mean glucose \<100mg/dl. |
| Intensive Care Admissions | at birth, up to 41 weeks | Number of participants with incidence of neonatal intensive care unit admissions |
| Delivery Mode | at birth, up to 41 weeks | method of delivery including cesarean section, vaginal delivery, or assisted vaginal delivery - data not collected |
| Birth Rate | at birth, up to 41 weeks | Number of live birth rate |
| Shoulder Dystocia | at birth, up to 41 weeks | Incidence of shoulder dystocia - data not collected |
| Polyhydramnios | at each visit in pregnancy up to 41 weeks | Incidence of polyhydramnios (defined as amniotic fluid index (AFI)\>20 or deepest vertical pocket ≥8) - data not collected |
| Neonatal Hypoglycemia | at birth, up to 41 weeks | Number of participants with incidence of blood sugar \<40mg/dl in neonate |
| Neonatal Bilirubin | at birth, up to 41 weeks | Percentage of neonatal hyperbilirubinemia - data not collected |
Countries
United States
Participant flow
Recruitment details
Women with gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (T2DM) who entered the Diabetes in Pregnancy Program were recruited from March 2013 through October 2014
Participants by arm
| Arm | Count |
|---|---|
| Insulin NPH Insulin neutral protamine Hagedorn | 42 |
| Levemir Insulin detemir (IDet) | 45 |
| Total | 87 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | allergic reaction | 6 | 0 |
| Overall Study | lack of insurance | 0 | 2 |
| Overall Study | Lost to Follow-up | 2 | 2 |
| Overall Study | switched to oral hypoglycemic or diet | 2 | 4 |
Baseline characteristics
| Characteristic | Insulin NPH | Levemir | Total |
|---|---|---|---|
| Age, Continuous | 35 years | 35 years | 35 years |
| Chronic hypertension | 5 Participants | 6 Participants | 11 Participants |
| GDM in previous pregnancies | 8 Participants | 9 Participants | 17 Participants |
| Gestational age at entry to DIPP | 27.3 weeks | 28.1 weeks | 27.5 weeks |
| Gestational age diagnosed | 26.1 weeks | 26.6 weeks | 26.3 weeks |
| Gestational age insulin started | 29.6 weeks | 30.0 weeks | 30.0 weeks |
| Multiple gestation | 2 Participants | 3 Participants | 5 Participants |
| Polycystic ovary syndrome | 5 Participants | 12 Participants | 17 Participants |
| Prepregnancy body mass index | 28.3 kg/m^2 | 28.6 kg/m^2 | 28.4 kg/m^2 |
| Prepregnancy body status Morbidly obese | 4 Participants | 3 Participants | 7 Participants |
| Prepregnancy body status Normal | 11 Participants | 14 Participants | 25 Participants |
| Prepregnancy body status Obese | 14 Participants | 12 Participants | 26 Participants |
| Prepregnancy body status Overweight | 12 Participants | 16 Participants | 28 Participants |
| Previous management Diet | 35 Participants | 39 Participants | 74 Participants |
| Previous management Diet, Metformin | 0 Participants | 1 Participants | 1 Participants |
| Previous management Glyburide | 3 Participants | 2 Participants | 5 Participants |
| Previous management Metformin | 3 Participants | 2 Participants | 5 Participants |
| Previous management Metformin and glyburide | 1 Participants | 0 Participants | 1 Participants |
| Previous management Other type of insulin | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Biracial/Multiracial | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black | 7 Participants | 5 Participants | 12 Participants |
| Race/Ethnicity, Customized Hispanic | 12 Participants | 15 Participants | 27 Participants |
| Race/Ethnicity, Customized Native American/Alaskan | 12 Participants | 6 Participants | 18 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 11 Participants | 17 Participants | 28 Participants |
| Renal disease | 1 Participants | 5 Participants | 6 Participants |
| Sex: Female, Male Female | 42 Participants | 45 Participants | 87 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| T2DM | 7 Participants | 7 Participants | 14 Participants |
| Thyroid disease | 6 Participants | 8 Participants | 14 Participants |
| Time between visits | 1.5 weeks | 1.5 weeks | 1.5 weeks |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 52 | 0 / 53 |
| other Total, other adverse events | 27 / 52 | 45 / 53 |
| serious Total, serious adverse events | 0 / 52 | 0 / 53 |
Outcome results
Primary
Glycemic Control
Overall mean glucose value of pregnancy. This will be determined by the sum of average glucose value at each visit, divided by the number of visits.
Time frame: up to 41 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin NPH | Glycemic Control | 109.5 mg/dL | Standard Deviation 10 |
| Levemir | Glycemic Control | 107.4 mg/dL | Standard Deviation 7.1 |
Secondary
Average Fasting Glucose
Mean fasting blood glucose in pregnancy, as determined by the sum of the mean fasting glucose at each visit divided by the number of visits
Time frame: up to 41 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin NPH | Average Fasting Glucose | 100.7 mg/dL | Standard Deviation 10.1 |
| Levemir | Average Fasting Glucose | 97.3 mg/dL | Standard Deviation 7.4 |
Secondary
Birth Rate
Number of live birth rate
Time frame: at birth, up to 41 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Insulin NPH | Birth Rate | 42 Participants |
| Levemir | Birth Rate | 45 Participants |
Secondary
Delivery Mode
method of delivery including cesarean section, vaginal delivery, or assisted vaginal delivery - data not collected
Time frame: at birth, up to 41 weeks
Secondary
Gestational Age at Delivery
Gestational age at delivery
Time frame: at delivery, up to 41 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Insulin NPH | Gestational Age at Delivery | 38.9 weeks |
| Levemir | Gestational Age at Delivery | 38.8 weeks |
Secondary
Intensive Care Admissions
Number of participants with incidence of neonatal intensive care unit admissions
Time frame: at birth, up to 41 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Insulin NPH | Intensive Care Admissions | 3 Participants |
| Levemir | Intensive Care Admissions | 6 Participants |
Secondary
Maternal Hypoglycemia
Number of participants with incidence of maternal hypoglycemia (\<60mg/dl)
Time frame: at delivery, up to 41 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Insulin NPH | Maternal Hypoglycemia | 11 Participants |
| Levemir | Maternal Hypoglycemia | 16 Participants |
Secondary
Neonatal Bilirubin
Percentage of neonatal hyperbilirubinemia - data not collected
Time frame: at birth, up to 41 weeks
Secondary
Neonatal Hypoglycemia
Number of participants with incidence of blood sugar \<40mg/dl in neonate
Time frame: at birth, up to 41 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Insulin NPH | Neonatal Hypoglycemia | 0 Participants |
| Levemir | Neonatal Hypoglycemia | 2 Participants |
Secondary
Neonatal Weight
Neonatal weight was estimated for occurrence of neonatal macrosomia (≥4000g birth weight) and neonatal LGA(large for gestational age)(birth weight \>90th percentile for gestational age
Time frame: At delivery, up to 41 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Insulin NPH | Neonatal Weight | 3230 g |
| Levemir | Neonatal Weight | 3235 g |
Secondary
Number of Patients Obtaining Glycemic Control
Number of each group that obtains glycemic control, defined as mean glucose \<100mg/dl.
Time frame: up to 41 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Insulin NPH | Number of Patients Obtaining Glycemic Control | 28 Participants |
| Levemir | Number of Patients Obtaining Glycemic Control | 35 Participants |
Secondary
Polyhydramnios
Incidence of polyhydramnios (defined as amniotic fluid index (AFI)\>20 or deepest vertical pocket ≥8) - data not collected
Time frame: at each visit in pregnancy up to 41 weeks
Secondary
Post-prandial Blood Glucose
Mean post-prandial blood glucose in pregnancy, as defined as the sum of the average post-prandial blood glucose at each visit divided by the number of visits.
Time frame: up to 41 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin NPH | Post-prandial Blood Glucose | 115.2 mg/dL | Standard Deviation 10.2 |
| Levemir | Post-prandial Blood Glucose | 112.9 mg/dL | Standard Deviation 8.9 |
Secondary
Shoulder Dystocia
Incidence of shoulder dystocia - data not collected
Time frame: at birth, up to 41 weeks
Secondary
Time to Achieve Glycemic Control
Time (weeks) to achieve glycemic control, as defined as mean glucose \<100mg/dl
Time frame: up to 41 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Insulin NPH | Time to Achieve Glycemic Control | 5 weeks |
| Levemir | Time to Achieve Glycemic Control | 5 weeks |
Secondary
Weight Gain
Total weight gain in pregnancy
Time frame: Number of pounds gained at each visit up to 41 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin NPH | Weight Gain | 27.7 lbs | Standard Deviation 15.3 |
| Levemir | Weight Gain | 28.6 lbs | Standard Deviation 11.6 |