The study investigates whether additional metformin medication in combination with regular insulin treatment will decrease the need of insulin for women with diabetes mellitus type 1 during pregnancy.
Insulin resistance during pregnancy of diabetes mellitus type 1 patients (DM1) increases the need for insulin and makes it more difficult to maintain normoglycemia. Fetal exposure to hyperglycemia induces macrosomia which increases fetal and neonatal morbidity and mortality. Further more obesity and excess weight gain during pregnancy enhances insulin resistance and it's an independent risk factor for fetal macrosomia. Metformin is a medical treatment for type 2 diabetes (DM2) where consequential pathophysiology includes insulin resistance. It reduces hepatic glucose production and enhances the use of glucose in muscles relieving insulin resistance. Metformin has also found to inhibit weight gain effectively. Metformin has approved to be safe and effective in patients with gestational diabetes (GDM). It has found to reduce weight gain and improve postprandial blood glucose levels during pregnancy and reduce neonatal birth trauma in GDM. However, there are no previous studies about the use of metformin in pregnant women with DM1. Two hundred women with DM1 will be randomized to get placebo or metformin in addition to regular insulin treatment. The sample size has been estimated to demonstrate the difference of 15 % in the need to increase insulin dosages during the pregnancy between the study groups.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
101
metformin 500 mg tablets and insulin
Placebo tablets mimic metformin 500 mg tablets and insulin
Helsinki University Hospital
Helsinki, Finland
Central Finland Health Care District
Jyväskylä, Finland
Oulu University hospital
Oulu, Finland
Tampere University Hospital
Tampere, Finland
Turku University Hospital
Changes in the insulin need during pregnancy
The insulin dosage (IU/ml) in two weeks sets
Time frame: from 5-10 gestational weeks until the delivery
Blood glucose balance during pregnancy HbA1c
HbA1c (mmol/mol)
Time frame: from gestational weeks 5 until the delivery
Blood glucose balance during pregnancy AVG, SD, CV
mean blood glucose (mmol/l) level, standard deviation (SD) and the coefficient of variation of the blood glucose levels
Time frame: from gestational weeks 5 until the delivery
Change in the weight
Weight gain (g) during pregnancy
Time frame: from gestational weeks 5 until the delivery
Change in the blood pressure
Blood pressure (mmHg)
Time frame: from gestational weeks 5 until the delivery
Incidence of pre-eclampsia
Incidence of pre-eclampsia (%)
Time frame: from gestational weeks 20 until the delivery
Incidence hepatogestosis
Incidence hepatogestosis (%)
Time frame: from gestational weeks 20 until the delivery
Pregnancy complications
Incidence proteinuria (mg/mmol or mg/d)
Time frame: from gestational weeks 5 until the delivery
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Turku, Finland
macrosomia
estimated fetal weight in ultrasound (grams)
Time frame: from gestational weeks 20 until the delivery
Pregnancy complications
incidence of miscarriage (intrauterine death before 22 weeks of gestation or fetal weigth under 500g) (%)
Time frame: 12-22 weeks of gestation
Pregnancy complications
incidence of intrauterine death (intrauterine death after 22 weeks of gestation or fetal weigth over 500g) (%)
Time frame: 22-40 weeks of gestation
Thigh fractional volume ultrasound
Fetal weight estimation (g) is specified by thigh fractional volume ultrasound program
Time frame: from gestational weeks 20 until delivery
Rate of the caesarean sections
Rate of the caesarean sections (%)
Time frame: The delivery
Labour
rate of spontaneous delivery (%)
Time frame: The delivery
Rate of the operative vaginal deliveries
Rate of the operative vaginal deliveries (%)
Time frame: The delivery
Rate of the shoulder dystocia
Rate of the shoulder dystocia (%)
Time frame: The delivery
Labor complications
rate of induced delivery (%)
Time frame: The delivery
Rate of the perineal tears
Rate of the perineal tears (%)
Time frame: The delivery
Postpartum bleeding
postpartum bleeding (ml)
Time frame: The delivery
Newborn variables (gestational age)
Rate of the premature deliveries (=deliveries before 37 weeks of gestation) (%)
Time frame: After the delivery
Newborn variables
weight of the newborn (g)
Time frame: After the delivery
Newborn outcome
Acidosis of the newborn (pH)
Time frame: After the delivery
Newborn outcome (intensive care)
The need of NICU (neonatal intensive care unit) treatment (days)
Time frame: After the delivery
Newborn outcome (hypoglycemia)
The occurrence of hypoglycemia (=plasma glucose under 2.6mmol/l or usage of iv glucose infusion) (%)
Time frame: After the delivery
Newborn outcome (Erb's)
Incidence of the Erb's paresis (%)
Time frame: After the delivery
Cost benefit calculations (sick leaves)
The need of sick leaves during pregnancy (days)
Time frame: from gestational weeks 12 until delivery
Cost benefit calculations (visits to maternity outpatient clinic or internal medicine policlinic)
The need of polyclinical controls during pregnancy (number of visits/pregnancy)
Time frame: 14-40 weeks of gestation
Cost benefit calculations (hospitalization)
The need of hospitalization during pregnancy (days/pregnancy)
Time frame: 14-40 weeks of gestation
Cost benefit calculations (all outpatient visits after delivery )
The need of policlinical controls of the diabetic mother after the delivery (number of visits)
Time frame: One year after the delivery
Cost benefit calculations (hospitalization after delivery, all departments)
The need of hospitalization of the diabetic mother after the delivery (days)
Time frame: Up to one year after the delivery
Cost benefit calculations (all hospitalization of the child)
The need of hospitalization of the child (days)
Time frame: Until the age of one year
Cost benefit calculations (all policlinical controls of the child)
The need of policlinical controls of the child (number of visits)
Time frame: Until the age of one year
high sensitive-CRP
high sensitive-CRP (mg/l)
Time frame: 7-10, 26-28 and 34-36 weeks of gestation
lipids
cholesterol, high density lipoprotein, low density lipoprotein, triglyserids (mmol/l)
Time frame: 7-10, 26-28 and 34-36 weeks of gestation
Inflammatory markers
adiponectin, leptin, resistin, IL-6, TNF-α (pg/ml)
Time frame: 7-10, 26-28 and 34-36 weeks of gestation