Pathophysiology
Gestational Diabetes Mellitus (GDM) develops when there is not enough insulin secreted during pregnancy to control the rise in blood glucose levels.
Insulin is a hormone formed in the pancreas. Insulin helps the body to use glucose for energy and helps control your blood glucose levels (Kinalski et al., 2002).
When insulin binds to its receptors, it activates several protein processes necessary for synthesis of glucose, glycogen and fatty acid synthesis, besides glycolysis process (Poulakos et al., 2015).
It is unknown yet the exact mechanisms causing Gestational Diabetes Mellitus (GDM)(Poulakos et al., 2015). It is thought that pregnancy hormones may interfere with insulin action by binding to its receptors and replacing it, this is called (insulin resistance) (Kahn, 2003).
As insulin activates glucose influx into most cells, then insulin resistance would prevents occurrence of this action. And so glucose would remain in the bloodstream; this means the rise of glucose levels (Vambergue et al., 2002). As a consequence, more insulin would be needed to resolve this resistance; which could be about 1.5 to 2.5 times more in the normal pregnancy, to insure enough glucose and nutrients supply to the fetus, so it can grow. This means also that insulin resistance is something normal which arises in the second trimester of pregnancy, but it could further progress to levels equivalent to type 2 diabetes levels (Becquet et al., 2016).
Placental hormones, like cortisol and progesterone, also may mediate insulin resistance during pregnancy, but human placental lactogen, prolactin and estradiol in addition to other placental hormones, leptin, tumor necrosis factor alpha, and resistin are involved also in the decrease in insulin resistance during pregnancy (Becquet et al., 2016).
Effects & Complications
Gestational Diabetes Mellitus (GDM) poses a risk to both mother and child. This risk is largely related to and increased with uncontrolled higher blood glucose levels and its consequences. Treatment and good control of these levels can reduce many of these risks considerably(Lee et al., 2007).
Untreated or uncontrolled Gestational Diabetes Mellitus (GDM) can cause problems for the baby, such as:
• Babies might be born with a body larger than normal—a condition called macrosomia—as extra glucose in mother's bloodstream crosses the placenta, which stimulates baby's pancreas to secrete more insulin, which in turn makes baby grow too large (Obstetricians and Gynecologists, 2000). Very large babies —of weight more than 9 pounds (4.1 kilograms)— are prone to risk of being stuck into the birth canal during vaginal delivery, causing problems like shoulder dystocia; when baby’s head passes through vagina, but baby’s shoulder gets stuck behind pelvic bone. Shoulder dystocia can be dangerous, as baby may be unable to breathe easily while stuck (Draycott et al., 2008). These problems make C-section more preferred, or early delivery may be recommended, in such case.
• Babies also might be born early (preterm birth) with respiratory distress syndrome. Gestational Diabetes Mellitus (GDM) increases the risk of early labor and delivery before due date. Dysmature babies are prone to respiratory distress syndrome due to incomplete lung maturation and impaired surfactant synthesis which makes breathing difficult. Babies with this syndrome may need help with breathing until their lungs become mature and more strong (Brower et al., 2004).
• Babies also might be born with jaundice, in which the skin and whites of the eyes become yellow. Jaundice usually disappears, when the baby gets enough breastfeeding with the help of phototherapy (Ross, 2006).
• Babies also may develop hypoglycemia (Low blood sugar) shortly after birth because their bodies secretes higher amounts of insulin. Severe hypoglycemia may trigger seizures in the baby, which may require admission to a neonatal intensive care unit for quick intervention with good feedings and administration of intravenous glucose solution to return blood sugar to normal levels (Cryer et al., 2003).
• Babies of mothers who have untreated Gestational Diabetes Mellitus (GDM) may be at risk of developing Type 2 diabetes and obesity later in life (Bellamy et al., 2009).
• Untreated Gestational Diabetes Mellitus (GDM) also could lead to baby death either before birth or shortly after it (Bellamy et al., 2009).
Untreated or uncontrolled Gestational Diabetes Mellitus (GDM) may also increase the mother's risk of:
• Having high blood pressure (hypertension) and too much protein in the urine (proteinuria), a condition called preeclampsia (Redman and Sargent, 2005). Preeclampsia usually occurs during the third trimester of pregnancy. If it isn't treated, it can cause several problems for both mother and baby and may lead to death. The only cure for preeclampsia is to give birth, or may be the need to have a cesarean section to deliver the baby early (preterm birth) (Redman and Sargent, 2005, Sibai, 2003). If preeclampsia develops earlier, the mother may need bed rest and medicines, or has to be hospitalized for adequate care for both her and the baby(Redman and Sargent, 2005).
• Getting depressed. Depression in turn can make her too tired and feel sad, nervous or unable to accommodate with the changes she is facing (Musselman et al., 2003).
• Developing type 2 diabetes and all of its related problems (Dunne et al., 2003).
Risk factors
Every woman should seek health care early, if possible — when she first think about trying to get pregnant — so her doctor can evaluate her risk of Gestational Diabetes Mellitus (GDM). If she develops it, she may need more frequent screening and checkups. These are most likely to occur during the third trimester (last three months) of pregnancy, when the doctor will monitor blood sugar level and baby's health (MacNeill et al., 2001).
Common risk factors for developing Gestational Diabetes Mellitus (GDM) are:
• Polycystic Ovary Syndrome (PCOS), a common endocrine system disorder that develops among women in child-bearing age. It is characterized by enlarged ovaries that contain small collections of fluid — called follicles — located in each ovary which could be seen during the ultrasound examination. It may lead to infrequent or prolonged menstrual periods, excess hair growth, acne, and obesity (Toulis et al., 2009).
• Previous history of Gestational Diabetes Mellitus (GDM), pre-diabetes, impaired glucose tolerance, or impaired fasting glycaemia.
• Family history of a first-degree relative with type 2 diabetes.
• Old maternal age; this risk factor increases as woman gets older, especially for women whose age is over 35 or 45 years.
• Ethnicity; those with higher risk factors are Non-white race; including African-Americans, Afro-Caribbeans, Native Americans, Hispanics, Pacific Islanders, and people originating from South Asia (MacNeill et al., 2001).
• Obesity increases the risk; when body mass index (BMI) is 30 or higher (Mokdad et al., 2003).
• A previous pregnancy which resulted in a baby born with a macrosomia (weighed more than 9 pounds (4.1 kilograms))
• Previous poor obstetric history (Di Cianni et al., 2003)
• Other genetic risk factors; There are at least 10 genes when certain polymorphism occurs to them, it may cause an increased risk of Gestational Diabetes Mellitus (GDM), most notably TCF7L2 gene (Zhang et al., 2013).
• Statistics show a double risk of Gestational Diabetes Mellitus (GDM) among smokers (Di Cianni et al., 2003).
There is no demonstrable risk factor, nor symptoms in about 40–60% of women suffering from Gestational Diabetes Mellitus (GDM); so all women must be screened. Some other women may suffer from some of common symptoms of diabetes, like increased thirst, increased urination, fatigue, nausea and vomiting, bladder infection, yeast infections and blurred vision (MacNeill et al., 2001).
Most women who have well controlled Gestational Diabetes Mellitus (GDM) deliver healthy babies. However, Gestational Diabetes Mellitus (GDM) that's not carefully managed can lead to uncontrolled blood sugar levels and cause problems for both the mother and the baby, including an increased potential of C-section delivery (Jensen et al., 2001).
Diagnosis & Screening
WHO diabetes diagnostic criteria
Condition 2-hour glucose Fasting glucose HbA1c
Unit mg/dl mg/dl mmol/mol DCCT %
Normal <140 <110 <42 <6.0
Impaired fasting glycaemia
<140 ≥110
&
<126 42-46 6.0–6.4
Impaired glucose tolerance
≥140 <126 42-46 6.0–6.4
Diabetes mellitus
≥200 ≥126 ≥48 ≥6.5
Blood tests are commonly used for diagnosing Gestational Diabetes Mellitus (GDM). There are many screening and/or diagnostic tests for detecting high levels of glucose in blood plasma or serum (TA, 2014).
Non-challenge blood glucose tests measure glucose levels in blood samples without challenging or forcing the person to drink a glucose solution, in contrast, challenge tests measure glucose levels in blood samples after forcing the person to drink a glucose solution, then blood glucose level is determined when fasting, 2 hours after a meal (postprandial), or at any random time (Mellitus, 2005).
Non-challenge blood glucose test:
Diagnosis of Gestational Diabetes Mellitus (GDM) is made, when a plasma glucose level is higher than 126 mg/dl after fasting, or over 200 mg/dl on any random time, and then confirmed on the following day, and no further testing is required after that (Nielsen et al., 2012).
When it is performed: At the first antenatal visit.
Advantages: Simple administration and inexpensive
Disadvantages: Lower test performance compared to the other tests, moderate sensitivity, low specificity and high false positive rates (Nielsen et al., 2012).
Screening glucose challenge test (O'Sullivan test):
Diagnosis of Gestational Diabetes Mellitus (GDM) is made, when a plasma glucose level is 140 mg/dl after 1 hour of drinking a glucose solution containing 50 g of glucose (Palmert et al., 2002).
When it is performed: Between 24–28 weeks of pregnancy.
Advantages: No previous fasting is required, simple and inexpensive
Disadvantages: Glucose solution could cause nausea in some women, so artificial flavors could be added.
Oral glucose tolerance test (OGTT):
This should be done in the morning after fasting overnight (8-14 hours).
The person must have unrestricted diet and physical activity during the last 3 days. The test involves drinking a glucose solution, containing 100 g of glucose, then withdrawing blood samples to measure glucose levels at the start and on set time intervals (after 1, 2 and 3 hours) thereafter (Stumvoll et al., 2000).
Diagnosis of Gestational Diabetes Mellitus (GDM) is made, when:
• Fasting blood glucose level ≥95 mg/dl
• 1 hour blood glucose level ≥180 mg/dl
• 2 hour blood glucose level ≥155 mg/dl
• 3 hour blood glucose level ≥140 mg/dl
Urinary glucose testing:
Women with Gestational Diabetes Mellitus (GDM) may have high glucose levels in their urine (glucosuria). Dipstick test, which is a stripe containing reagent for detecting glucose in urine, is widely used, although it performs poorly; as the sensitivity of glucosuria for Gestational Diabetes Mellitus (GDM) in the first 2 trimesters is only around 10% (Goldstein et al., 2004).