Essay: Gestational Diabetes Mellitus (GDM) analysis

Introduction

Gestational Diabetes Mellitus (GDM) is a condition that affects women during pregnancy (gestation), where blood glucose levels are increased above normal limits (Baz et al., 2015).

Blood glucose levels are controlled normally by insulin hormone (Kinalski et al., 2002). But some pregnant women may have higher levels of glucose that can’t be managed by insulin secreted in their bodies (Kleinwechter et al., 2014).

Diabetes Mellitus, other than GDM, could be:

• Type 1 diabetes  – in which the body doesn’t secrete insulin hormone at all (mostly called ‘juvenile diabetes’) (Toyoda, 2002).
• Type 2 diabetes – in which the body doesn’t secrete enough insulin and/or there is insulin resistance (cells don’t react to insulin) (Toyoda, 2002)

Gestational Diabetes Mellitus (GDM) usually arises after 28 weeks, in the third trimester, of pregnancy, and usually disappears after delivery (Association, 2010). Women with Gestational Diabetes Mellitus (GDM) are prone to risk of preeclampsia and Caesarean section (Ross, 2006) in addition to developing type 2 diabetes later (Dunne et al., 2003), so they should monitor their blood glucose levels and manage it with their physicians (Kim, 2010).

Gestational Diabetes Mellitus (GDM) symptoms and signs are very few in general, and mostly diagnosed by screening tests of higher levels of glucose in blood samples withdrawn during pregnancy (Kalelioglu et al., 2007).

Epidemiology

About 3 to 10% of pregnant women are affected with Gestational Diabetes Mellitus (GDM), according to several factors (Chanprapaph and Sutjarit, 2004). If they are not treated, they would deliver infants at high risk of clinical problems, for example being larger than normal (macrosomia) which may cause delivery complications), jaundice and hypoglycemia (Kinalski et al., 2002). This can also lead to seizures or being born dead (stillbirth) (Kinalski et al., 2002). Gestational Diabetes Mellitus (GDM) could be treated and women can decrease these risks effectively by controlling of glucose levels in their blood (Erem et al., 2015). This control could be achieved by following a healthy eating plan and keeping active and physical exercises, and if this doesn’t work, then using anti-diabetic drugs, including insulin, would be necessary (Erem et al., 2015).

Classification

Gestational Diabetes Mellitus (GDM) has another definition which is “any degree of glucose intolerance during pregnancy”(Buchanan and Xiang, 2005).

This definition may indicate that pregnant woman hasn’t been diagnosed with diabetes mellitus previously, or she may have developed diabetes mellitus simultaneously with pregnancy (Buchanan and Xiang, 2005).

Diabetes Mellitus could be classified into two groups according to this definition, which are Gestational Diabetes Mellitus (type A) and Pregestational Diabetes Mellitus (prior to pregnancy) (Association, 2010).

Furthermore, These two groups are classified according to their related risks and how to manage them (Association, 2010).
Gestational Diabetes Mellitus (GDM) is divided into:

• Type A1: In which oral glucose tolerance test (OGTT) is abnormal, but during fasting and two hours postprandial, blood glucose levels are normal; so following healthy diet would be sufficient for management (Mellitus, 2005).
• Type A2: In which oral glucose tolerance test (OGTT) is abnormal and during fasting and two hours postprandial, blood glucose levels are abnormal too; management would necessarily include the use of anti-diabetic drugs like insulin or other (TA, 2014).

Pregestational Diabetes Mellitus is also divided into many subtypes (TA, 2014):

• Type B: onset at age 20 or older or duration of fewer than 10 years.
• Type C: onset at age 10–19 or duration of 10–19 years.
• Type D: onset before age 10 or duration of more than 20 years.
• Type E: obvious diabetes mellitus with calcified (rigid) pelvic vessels.
• Type F: diabetic nephropathy.
• Type R: proliferative retinopathy.
• Type RF: retinopathy and nephropathy.
• Type H: ischemic heart disease.
• Type T: prior kidney transplant.

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).
Prevention

Ways that can lower the risk of getting Gestational Diabetes Mellitus (GDM) (Ratner et al., 2008):

• Losing extra weight: Pregnancy could lead to little increase of body weight, which is something good for baby health, but gaining too much weight in a very quick manner may increase the risk of getting Gestational Diabetes Mellitus (GDM) (Ratner et al., 2008).
• Increasing physical activity level before pregnancy is effective for the prevention of Gestational Diabetes Mellitus (GDM) (Sanabria‐Martínez et al., 2015).
• Smoking cessation also may decrease the risk of Gestational Diabetes Mellitus (GDM).
• Monitoring blood glucose levels regularly.
• Follow a healthy eating plan. Eating more grains, fruits, and vegetables. Cutting down on fat and calories (Kim et al., 2007).

Healthy Eating Plan

An important factor of managing Gestational Diabetes Mellitus (GDM) is diet (Reader et al., 2006). Following a healthy eating plan will assist in:

• Managing blood glucose levels within normal limits
• Providing adequate nutrition for mother and growing fetus
• Achieving appropriate weight changes during pregnancy (Kim et al., 2007).

Women with Gestational Diabetes Mellitus (GDM) are encouraged to (Reader et al., 2006):

• Eat small amounts and maintain a healthy weight.
• Include some carbohydrate in every meal and snacks (e.g. Multigrain bread, bulgur, pasta, potato, lentils, chickpeas, beans)
• Choosing foods that provide nutrients especially needed during pregnancy. These may include: calcium (e.g. Milk and cheese), iron

(e.g. Red meat, chicken and fish), folic acid (e.g. Dark green leafy vegetables lightly cooked, low in fat, particularly saturated fat (e.g. use oils such as canola, olive and polyunsaturated oils and margarines and use lean meats such as skinless chicken and low fat dairy foods)

• Choosing foods of high fiber content
• Avoiding foods and drinks which contain large amounts of sugar
• Choosing Basmati or Doongara rices as they have a lower glycemic index (low glucose amounts) and will help to stay fuller for longer.

Carbohydrates

Carbohydrate foods are broken down into glucose which is utilized for energy. To help managing blood glucose levels, it is important to distribute carbohydrate foods over three small meals and 2-3 snacks each day (Zhang et al., 2006a).
Foods that contain carbohydrate include:

• Multigrain breads and breakfast cereals
• Pasta, rice (preferably Basmati or Doongara) and noodles
• Potato (in moderation), sweet potato and corn
• Legumes such as baked beans, red kidney beans and lentils
• Fruits
• Milks and yoghurts

N.B. sucrose (table sugar), soft drinks, cordials, fruit juices, lollies, cakes and biscuits are of little nutritional value (Zhang et al., 2006a).

Fat

Eating fats, especially saturated fat, should be limited. It is recommended to use healthy fats like canola, olive and polyunsaturated oils and margarines, avocados and unsalted nuts. To limit saturated fat intake, select lean meats, skinless chicken and low-fat dairy foods and avoid takeaway and processed foods (Liang et al., 2010).

Protein

Two small serves of protein each day is recommended as protein is important for the growth of fetus and maintenance of healthy mum. Protein foods include lean meat, skinless chicken, fish, eggs and reduced fat cheese (Zhang et al., 2006b, Kim et al., 2007).
These foods do not directly affect blood glucose levels. Milk, yoghurts, custards and legumes (beans, lentils, and chickpeas) are also important sources of protein and carbohydrates (Zhang et al., 2006b).

Calcium & iron

Calcium and iron requirements increase during pregnancy. So two serves of low fat calcium rich foods should be included each day. (One serve = 250 ml milk, 200 g of yoghurt or 2 slices of cheese). The iron from red meat, chicken and fish is readily absorbed (Zhang et al., 2006b).

Other dietary considerations

Nutritious foods that will not cause excess weight gain or cause increase of blood glucose levels can be eaten freely. These foods include fruits such as strawberries, passion fruit, lemons and limes and all vegetables (except potato, corn, sweet potato, taro, beans, lentils and chickpeas) (Zhang et al., 2006b).

Drinks

The best drink for the body is water, plain mineral water and soda water – it is recommended with fresh lemon or lime as something different. Sugar-free ‘diet’ drinks are preferred for people with diabetes (Gray-Donald et al., 2000).

However carbonated and caffeinated varieties can increase the risk of osteoporosis and may affect mood so should be consumed in moderation by everyone (Gray-Donald et al., 2000).

Alternative sweeteners

Alternative sweeteners is more preferable than to natural sugars.

Physical activity

For women with Gestational Diabetes Mellitus (GDM), moderate intensity physical activity is recommended as it can help to manage blood glucose levels, however, it is preferred to discuss with obstetrician or midwife prior to commencing any exercise regime in pregnancy (Sanabria‐Martínez et al., 2015).

Benefits of Physical activity

Physical activity helps to reduce insulin resistance (Sanabria‐Martínez et al., 2015). Regular exercise, like walking, helps to increase fitness and prepares the mother for the birth of her baby. Physical activity also helps to keep blood glucose levels under control (Sanabria‐Martínez et al., 2015).

How to walk more each day

• Walking to the local shops instead of driving.
• Starting a ‘walking group’ with family or friends – perhaps meet at a regular time and day.
• Taking the stairs instead of the elevator.
• Standing and moving while on the phone.
• Garden.
• Using a ‘pedometer’ (or a ‘step counter’).

Reducing the risk of developing type 2 diabetes

While maternal blood glucose levels usually return to normal after birth, there is an increased risk for the mother developing type 2 diabetes in the future (Retnakaran et al., 2007).

To reduce risk or delay the development of type 2 diabetes, it is recommended to (Ross, 2006):

• Maintain or achieve a healthy weight. Balanced food intake with activity levels is the best way to reduce any excess body weight.
• Eat healthily. Limit saturated fat. Choose lean meat, skinless chicken and low fat dairy foods. Limit processed and fried foods.
• Eat plenty of vegetables, legumes, fruits, wholegrain breads and cereals.
• Be physically active. Aim to include at least 30 minutes of moderate intensity physical activity on most days.
• Check blood glucose levels every 1-2 years at least (Vijan, 2010).

Treatment & Management

The purpose of treatment is to reduce the risks of Gestational Diabetes Mellitus (GDM) for both mother and child. Controlling glucose levels can lower fetal complications (such as macrosomia) and increase maternal health (Artal et al., 2007).
If a healthy diet, physical exercise, and oral medication are not enough to control glucose levels, insulin therapy would be necessary(Westermeier et al., 2015).

Lifestyle

Counseling before pregnancy (for example, about preventive folic acid supplements) (Artal et al., 2007).

Most women can manage their Gestational Diabetes Mellitus (GDM) by making healthy dietary changes and exercise activity, as mentioned above. Self-monitoring of blood glucose levels is an important factor to guide therapy (Saudek et al., 2006). Some women need anti-diabetic drugs, whereas most commonly need insulin therapy (Artal et al., 2007).

Self-monitoring could be achieved using a handheld capillary glucose dosage system (device used for measuring blood Glucose levels) (Tang et al., 2000).

Medication

If monitoring indicates failure of control of glucose levels with these measures, or if there is evidence of complications like excessive fetal growth, then treatment with insulin might be necessary (Westermeier et al., 2015).

Fast-acting insulin is commonly used just before eating meals. Care needs to be taken to avoid low blood sugar levels (hypoglycemia) because of excess insulin (Westermeier et al., 2015).

Certain oral anti diabetic drugs might be safe or less dangerous in pregnancy on the growing fetus than poorly controlled diabetes (i.e The lesser of two harms) (Zhu et al., 2016).

The oral medication metformin is better than glyburide. If blood glucose cannot be controlled enough with a single drug, then a combination of metformin and insulin may be better than insulin alone (Ashoush et al., 2016).

People may prefer metformin by mouth to insulin injections. Treatment of polycystic ovarian syndrome with metformin during pregnancy has been noted to decrease Gestational Diabetes Mellitus (GDM) levels (Song et al., 2016).

Metformin also lower the need for insulin, and help to gain less weight (Song et al., 2016).

Prognosis

Gestational Diabetes Mellitus (GDM) generally resolves once the baby is born. According to different studies, the potential of developing Gestational Diabetes Mellitus (GDM) in a second pregnancy, if first pregnancy developed Gestational Diabetes Mellitus (GDM), is between 30 and 84%, especially within one year of the previous pregnancy, depending on ethnic background (Nohira et al., 2006).

Women with Gestational Diabetes Mellitus (GDM) are subject to an increased risk rate of developing diabetes mellitus in the future, ( Type 2) (Nohira et al., 2006).

This risk is highest in case of women who:

• needed insulin treatment.
• had antibodies associated with diabetes ex. antibodies against glutamate decarboxylase, islet cell antibodies and/or insulinoma antigen-2.
• had more than two previous pregnancies
• were obese.

Women requiring insulin to manage Gestational Diabetes Mellitus (GDM) have a 50% risk of developing diabetes within the next five years (Lee et al., 2007).

Children of women with Gestational Diabetes Mellitus (GDM) have also an increased risk for childhood and adult obesity and an increased risk of glucose intolerance and type 2 diabetes later in life (Lee et al., 2007).