Madison Kotsonas ’22 and Delaney Rutherford ’22

All a pregnant woman longs for is a healthy, happy baby at the end of her pregnancy. While most women get their wish, the unfortunate reality is that some women have complications for several reasons. One potential complication is Gestational Diabetes Mellitus (GDM), which is when a mother becomes diabetic during her pregnancy. GDM occurs in 12% – 18% of all pregnancies, and the risk of developing this increases with age or a prior diagnosis of diabetes. Women diagnosed with GDM must undergo major diet and lifestyle changes to combat their increase in blood sugar levels. Multiple women discussed how they created restricted meal plans, walked or exercised more, took blood sugar measurements before and after each meal, and sometimes took insulin doses. It is important to educate people about the causes of GDM, as well as the short-term and long-term effects on the DNA of women and their children. Although GDM cannot always be prevented, it is important to understand how women can best help themselves and their children from the lasting effects of GDM. 

Normally, when a healthy woman has high blood sugar levels after eating a meal, pancreatic cells will promote insulin release. Insulin is a hormone or a signaling molecule, which regulates the conversion of blood sugar levels into energy for your body to use. Insulin will stimulate glucose—a sugar that is the main source of energy in your body—to leave the bloodstream and enter the liver for storage. This process allows women to maintain their blood sugar levels. However, pregnant women with GDM become resistant to insulin. This means glucose is not removed from their bloodstream, resulting in higher blood sugar levels. A pregnant woman’s blood concentration influences her baby because of the umbilical cord and placenta. The mother’s blood will pass through the placenta and then the umbilical cord filters glucose and other nutrients to the baby. So, when the mother has higher blood glucose levels, her baby does as well (Figure 1).

Figure 1: Gestational Diabetes Overview

Oftentimes, GDM is the first diagnosis of diabetes for women. Women don’t usually experience symptoms before their diagnosis, making it difficult to notice without testing. However, some women report symptoms of increased thirst, frequent urination, nausea, vomiting, and even blurred vision. An OBGYN normally conducts blood sugar tests in the woman’s second trimester which reveals the prognosis of GDM for most women. A woman’s chances of developing GDM may be higher due to a family history of GDM or diabetes. The risk of GDM may also increase with other factors such as higher age, poor lifestyle habits, and obesity during pregnancy. However, not all women who experience GDM are obese—indicating that other factors are also involved.

Sometimes, before women are even aware they have GDM, scientists can detect GDM based on abnormalities in their DNA and genes compared to healthy pregnant women. DNA, or deoxyribonucleic acid, is a molecule that contains instructions for how our bodies function, and it does this by regulating genes. A gene is a small stretch of DNA that is hereditary, meaning that it specifically controls which traits are passed down from parents to their offspring. However, despite the presence of these genes, some affect the body and others don’t at all. Whether a gene has an effect or not is regulated by a mechanism called epigenetics. Epigenetics is the study of gene expression changes that are not caused by random DNA mutations. Epigenetic modifications are similar to how humans use light switches, such that a gene can be turned on or off. Like how humans use their fingers to flip the switch, molecules bind and unbind to DNA which will turn the gene on or off. 

Scientists are discovering that women with GDM may have abnormal changes in their gene expression compared to normal. They are finding that the genes responsible for a woman’s ability to secrete, break down, and respond to insulin in the pancreas are not expressed, or “turned off,” when normally they are turned on. Therefore, since these genes are not expressed, women with GDM aren’t responding to insulin how they typically should. Scientists are drawing similarities between GDM and Type 2 Diabetes (T2D) since both conditions have similar altered gene expression patterns in the pancreas.

In addition to the presence of differential gene expression of the pancreatic cells in women with GDM, scientists are also detecting altered gene expression in genes specific to pregnancy. These are genes that a pregnant woman’s blood, umbilical cord, and placenta all share. While these genes are normally turned off, they are found to be turned on in women with GDM—which is linked to higher glucose levels and impaired insulin secretion. When these gene discrepancies increase the glucose levels in the woman’s blood, the baby will receive elevated glucose levels from the blood filtered through the umbilical cord and placenta. In addition to having higher blood glucose levels altogether, the baby may also experience similar altered gene expression to the mother after birth—potentially leading to T2D in the baby. 

Interestingly, there is a study on a maternal imprinting gene that found expression is turned on in obese women with GDM, which may be causing an increased risk of childhood obesity. Although these studies are still in the beginning stages and have only found correlational links, they are important in proving that GDM risk can be increased due to certain genes that are turned on and off. The inheritance of the proteins turning the genes on or off may be indicative of the cycle seen in women with GDM and the chances their child develops childhood obesity or T2D. This could lead to the development of GDM in the future, during the pregnancy of a daughter, possibly causing a cycle for generations (Figure 2). 

Figure 2: GDM Cycle 

Although it is still unknown why these genetic changes are appearing, Nutri-Epigenetics may be an explanation. Nutri-Epigenetics is the idea that nutritional intake can affect gene expression. If a pregnant woman has an unhealthy diet that causes her blood sugar to rise substantially, this may affect the genes in the fetus’ liver to express hormones such as leptin and adiponectin. These hormones regulate body weight and insulin sensitivity, respectively. When these genes are differentially expressed, it may increase the baby’s body weight, induce insulin resistance and, therefore, increase blood glucose levels. Some studies have found that higher fat diets during pregnancy may cause less proteins to be bound to the leptin gene and more proteins on the adiponectin gene in the fetus. This causes increased and decreased expression of these genes, respectfully. This may lead to metabolic syndromes that may cause obesity or an increased risk of T2D. These studies show that environmental factors such as nutrition may have some effect on developing GDM in conjunction with differential gene expression (Figure 3). 

Figure 3: Different Effects on Childhood Obesity and T2D 

A more recent study has researched a potential link between temperature and the likelihood of developing GDM. A study analyzed the development of GDM over 12 years in 396,828 women and 555,911 births. They recorded the average temperature in the environment at the time of the women’s pregnancy. They found an increased risk of GDM for women exposed to higher temperatures during their pregnancy (Figure 4). They also found that women who had multiple births sometimes developed GDM when one pregnancy occurred during a warmer temperature rather than the other pregnancy at a colder temperature. This study was conducted in Canada, so further research is needed to validate these results by tracking GDM prevalence in other areas of the world. Although this study is new and mostly looks at a correlational relationship, it has implications for possible climate change in the future. As the Earth starts to get warmer, an increase in GDM may occur. Since GDM may be linked to childhood obesity, the world may see this increase as well. Until a causal relationship can be established, this research remains preliminary and only represents a correlational theory with possible implications for women and children in the future. 

Figure 4: Correlation between temperature and GDM risk

If untreated, GDM can have many effects on pregnant women. During the pregnancy itself, the woman typically has increased blood glucose levels and high blood pressure. However, these effects are mostly resolved after the woman gives birth. Yet, high blood pressure could lead to a heightened risk of pre-eclampsia, which is when there is damage to the liver and kidneys. Additionally, most women either have preterm births or C-sections. Since the baby typically overgrows due to increased blood glucose levels, most women avoid vaginal delivery because it could result in physical birth trauma. For the mother, physical trauma could include tearing, swelling, or muscle damage. Beyond the birth itself, GDM sometimes leads to continued insulin resistance—which can increase the mother’s risk of developing T2D later in life. The incidence of the mother developing GDM in later pregnancies also increases. 

The baby is also likely to experience the effects of the mother’s GDM. If the baby grows larger, it is often around the head and shoulders. These areas are most likely to be injured during a vaginal birth delivery. Shoulder dystocia is when the baby’s shoulders get stuck in the woman’s pelvis which can lead to possible suffocation during birth. Following the birth, the baby can continue to have effects caused by GDM. The loss of the mother’s glucose can cause the baby to metabolize sugar faster than it can receive it, which may require treatment. The baby could also develop jaundice, which is when liver dysfunction causes yellowing of the baby’s skin. If left untreated, the baby could develop brain damage, termed kernicterus. Light therapy is usually enough to fix the effects of jaundice. Another post-birth effect could be the development of respiratory distress syndrome if the baby is born preterm, which may require oxygen therapy until the baby can breathe on its own.  

Although there is no cure to rid GDM in pregnant women, there are many measures that women can take to live healthily and minimize potential consequences. Doctors recommend a low-carb diet with natural sugars to maintain their blood glucose levels. This may be difficult because organic diets are often costly. One way to combat this could be taking more walks or increasing exercise to combat the effects of a higher-carb diet. Many women also maintain a caloric limit by eating less or even fasting at times during the day. This is not to say mothers should never eat, but taking extended breaks between meals or snacking on vegetables and nuts may help decrease blood glucose levels. Women who continue to work during their pregnancy may also find it hard to exercise regularly due to time constraints. Possibly taking short walks during a lunch break or at multiple points in the day would help increase exercise without dedicating too much time. Women with GDM also frequently take their blood sugar levels before and after every meal to ensure that their levels are not too high. If they are elevated, they may take insulin injections or other diabetic medications to lower them. Postpartum, women are initially closely observed and administered oxygen and glucose if needed. Altogether, taking the right measures during pregnancy is likely to minimize the effects of GDM on the mother and her baby after giving birth.

Despite the growing abundance of GDM, the attendance of follow-up treatment of women that were diagnosed is unsatisfactory. Many women do not seek follow-up treatment whilst experiencing GDM and even after giving birth. However, many women lack access to proper medical treatment for GDM, or insurance to cover appointment costs. Universal health care or more affordable health insurance could be a solution to increase follow-up appointments for women. Accessible education and inexpensive treatment are necessary for all pregnant women, who may or may not have GDM. Healthcare providers should promote awareness and education of what it means to have GDM and how it can be safely managed. As researchers continue to understand the mechanisms of this disorder, they should also focus on developing inexpensive treatments and diets to help pregnant women of any socioeconomic status. Gestational Diabetes is indeed real and is becoming a growing problem for pregnant women, especially in the US. While there are still so many unknowns about GDM, it is clear women and their healthcare providers can make a significant impact on both their and their baby’s health during and after the pregnancy.

References

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