Episode 193: Gestational Diabetes Intro

Jesica Mendoza (OMSIII) describes the pathophysiology of gestational diabetes and the right timing and method of screening for it. Dr. Arreaza adds insight into the need for culturally-appropriate foods, such as vegetables in Mexican cuisine.    

Written by Jesica Mendoza, OMSIII, Western University of Health Sciences, College of Osteopathic Medicine of the Pacific. Editing by Hector Arreaza, MD.

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Definition

Gestational diabetes mellitus (GDM) is a condition that occurs to previously non-diabetic pregnant women, caused by glucose intolerance at around the 24th week of gestation. 

Pathophysiology

GDM arises due to an underlying pancreatic beta cell dysfunction in the mother which leads to a decrease in the amount of insulin produced and thus leads to higher blood sugar levels during pregnancy. 

The placenta of the fetus will produce hPL (human placental lactogen) to ensure a steady supply of sugars to the fetus, creating an anti-insulin effect. However, hPL readily crosses the placental barrier causing the mothers insulin requirement to increase, when the mother’s pancreas cannot increase production of insulin to that level needed to counter the effect of hPL they become diabetic, and this leads to gestational diabetes. So, basically the placenta is asking for more glucose for the baby and the mother’s pancreas struggles to keep the glucose level within normal limits in the body of the mother. If left untreated, high levels of glucose in the mother can cause glucotoxicity in the mother.

“Glucotoxicity” refers to the toxic effect of glucose. Glucose is the main fuel for cell functions, but when it is high in the bloodstream, it causes toxicity to organs. 

Prevalence of GDM.

The CDC reports mean prevenance of GDM is 6.9%. In U.S. mothers the prevenance increased from 6.0% in 2016 to 8.3% in 2021. Many different factors have played a role in increasing gestational diabetes in American mothers, some of those being the ongoing obesity epidemic with excess body weight being a known risk factor for insulin resistance. 

Another being advanced maternal age (AMA) as more American women have children later in life their body becomes less sensitive to insulin and requires a higher insulin output on top of the insulin that is required for the fetus. 

The “American diet” is also something that has a big effect in diabetes development. With the increase of high-carb foods that are readily available, the diet of Americans has declined and is affecting the metabolic health of mothers as they carry and deliver their children. 

Despite ongoing awareness of GDM, 6% to 9% of pregnant women in the United States are diagnosed with gestational diabetes, and the prevalence continues to increase worldwide. It is estimated that in 2017 18.4 million pregnancies were affected by GDM in the world, which then continued to increase to 1 in 6 births to women with GDM in 2019. 

It was also found that women living in low-income communities were disproportionately affected due to limited healthcare access. Additionally, women with GDM had a 1.4-fold increase in likelihood of undergoing a c-section, with 15% increase in risk of requiring blood transfusion. 

Screening for GDM

Gestational diabetes is screened between the 24th to 28th week of gestation in all women without known pregestational diabetes. 

In women who have high-risk for GDM the screening occurs during the first trimester, these women usually have at least one of the following: BMI > 30, prior history of GDM, known impaired glucose metabolism, and/or a strong family history of diabetes. 

The screening during the first trimester is to detect “pregestational diabetes” because we have to keep a good glycemic control to improve outcomes of pregnancy. So, if it’s positive, you start treatment immediately. 

If these women are found to have a normal glucose, they repeat the testing again as done normally, at 24-28 weeks of gestation. 

How do we screen?

The screening itself consists of two types of approaches. The two-step approach includes a 50-gram oral glucose tolerance test (OGTT), where blood glucose is measured in an hour and if it is below 140 they are considered to not have GDM, however if the reading is greater than 140 they must then do a 3-hour, 100g oral glucose tolerance test. The 3-hour OGTT includes measuring the blood sugars at Fasting which should be less than 95, at 1 hour at less than 180, at 2 hours at less than 155, and at 3 hours at less than 140. If 2 or more of these values exceed the threshold the patient is diagnosed with gestational diabetes mellitus. 

The one-step approach includes 75g after an overnight fast. Blood glucose is measured while fasting which should be less than 92, at 1 hour less than 180 and at 2 hours less than 153. If any one of these values is exceeded, the patient is diagnosed with GDM.

If the mother is found to be GDM positive during pregnancy she will also need continued screening post-partum to monitor for any development of overt diabetes. The testing is usually 75g 2-hour OGTT at 6-12 weeks postpartum. If this testing is normal, then they are tested using HbA1c every 3 years. If the post-partum testing shows pre-diabetes, annual testing is recommended using HbA1c measurements. 

Maternal complications 

Women with GDM are at an increased risk for future cardiovascular disease, T2DM, and chronic kidney disease. GDM is also associated with increased likelihood of developing pre-eclampsia following delivery. Pre-eclampsia is a complication seen in pregnancy characterized by high blood pressure, proteinuria, vision changes, and liver involvement (high LFTs). Pre-eclampsia can then progress to eclampsia or HELLP syndrome, both of which can include end organ damage. 

Additionally, she can develop polyhydramnios which leads to overstretching of the uterus and can induce pre-term labor, placental abruption, and or uterine atony, all of which additionally put the mother at increased risk for c-section. 

All of these maternal complications that stem from GDM lead to complications and extended hospitalization. 

Child’s complications 

Although there is an increased set of risks for the mother, the neonate can also develop a variety of risks due to the increased glucose while in utero. While the fetus is growing, the placenta is the source of nutrition for the fetus. As the levels of glucose in the mother increase so does the amount of glucose filtered through the placenta and into the fetal circulation. Over time the glucose leads to oxidative stress and inflammation with activation of TGF-b which leads to fibroblast activation and fibrosis of the placenta. This fibrosis decreases the nutrient and oxygen exchange for the fetus. As the fetus attempts to grow in this restrictive environment its development is affected. 

The fetus can develop IUGR (intrauterine growth restriction) leading to a small for gestation age newborn which can then lead to another set of complications. The low oxygen environment can lead to increased EPO production and polycythemia at birth which can then lead to increased clotting that can travel to the newborn brain. 

Newborns can also be born with fetal acidosis due to the anerobic metabolism and lactic acid buildup in fetal tissues which can cause fetal encephalopathy leading to cerebral palsy and developmental delay. 

And the most severe of newborn complications to gestational diabetes can lead to fetal demise. 

Furthermore, the increase of glucose can also lead to macrosomia in the infant which can often lead to a traumatic delivery and delivery complications such as shoulder dystocia and brachial plexus injury. 

Brachial plexus injury sometimes resolves without sequela, but other times can lead to permanent weakness or paralysis of the affected arm. 

The baby can be born too small or too big.

Additionally, once the fetus is born the cutting of the umbilical cord leads to a rapid deceleration in blood glucose in the fetal circulation and hypoglycemic episodes can occur, that often lead to NICU admission. 

The insulin that is created by the fetus in utero to accommodate the large quantities of glucose is known to affect lung maturation as well. The insulin produced inhibits surfactant production in the fetus. Upon birth some of the newborns also have to be placed on PEEP for ventilation and some children require treatment with surfactant to prevent alveolar collapse and/or progression to NRDS created by the low surfactant levels. 

Additionally, neonates who are macrosomic, which is usually seen in GDM mothers, are larger and stronger and when put on PEEP to help increase ventilation the newborn’s stronger respiratory effort can lead to higher pulmonary pressures and barotrauma such as neonatal pneumothorax.

Long term complications to the child of a mother with GDM also occur. As the child grows, they are also at an increased risk for developing early onset obesity because of the increased adipose storage triggered by the increase in insulin in response to the high glucose in utero. This then can lead to a higher chance of developing type 2 diabetes mellitus in the child. With diabetes, also comes an increase in cardiovascular risk as the child ages and becomes an adult. The effects of GDM go beyond the fetal life but continue through adulthood.

What can be done?

Gestational Diabetes Mellitus has many severe and lifelong consequences for both the mother and the child and prevention of GDM would help enhance the quality of life of both. 

Many of the ways to prevent GDM complications include patient education and dietary modifications with a diet rich in whole grains, fruits, vegetables and lean proteins. 

Benefits of some vegetables in the Mexican cuisine that may be beneficial: Nopales, Chayote, and Jicama. Those are good alternatives for highly processed carbs.

Mothers are usually offered nutritional counseling to help them develop a tailored eating plan. This and 30 minutes of moderate exercise daily is recommended to increase insulin sensitivity and lower the post-prandial glucose levels. If within 2 weeks of implementing lifestyle changes alone the glucose measurements remain high, then medications like insulin can be put onboard to manage the GDM. 

If they require insulin, I think it is time to refer to a higher level of care, if available, high risk OB clinic.

Conclusion: Now we conclude episode number ###, “[TITLE].” [summary here]. 

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14. Theme song, Works All The Time by Dominik Schwarzer, YouTube ID: CUBDNERZU8HXUHBS, purchased from https://www.premiumbeat.com/.