The global prevalence of gestational diabetes mellitus (GDM) is about 17%, although closer to the 7-10% range specifically in the United States. GDM is associated with several perinatal complications, and those with pre-pregnancy diabetes, insulin resistance, and obesity are at higher risk for developing GDM. Although GDM does not need to be understood at the level of an OB/GYN, its risk factors and associations with obesity fall within the scope of obesity medicine specialists, making GDM a high-yield topic for the ABOM examination and the focus of this week’s blog.

Let’s start with a quick overview of the mechanism of GDM. To ensure that a growing fetus receives adequate nutrition to support healthy development, the placenta secretes several hormones that increase maternal insulin resistance. This physiologic process helps ensure that sufficient glucose crosses the placental barrier. Gestational diabetes mellitus (GDM) develops when the mother’s pancreatic β-cells are unable to produce a sufficient compensatory increase in insulin to overcome this pregnancy-induced insulin resistance.

Even though GDM is universally understood to be caused by increased maternal insulin resistance, its definition varies slightly between professional societies. The American Diabetes Association defines it as diabetes diagnosed after 15 weeks’ gestation in patients without a prior pre-conception diabetes history, whereas the American College of Obstetricians and Gynecologists define it more broadly as “a condition in which carbohydrate intolerance develops during pregnancy.”

Screening for GDM is generally performed between 24 and 28 weeks’ gestation using an oral glucose tolerance test. An early hemoglobin A1c to rule out pre-existing diabetes can be useful, but hemoglobin A1c as a screening tool during pregnancy lags behind. Recall that HbA1c measures the percentage of glycated hemoglobin within circulating red blood cells. As a result, it reflects past glucose exposure rather than the more acute insulin resistance that develops during pregnancy, potentially delaying the diagnosis of GDM. A previous diagnosis of GDM in prior pregnancies has a 40% risk in subsequent pregnancies. As briefly mentioned above, other risks of developing GDM include pre-pregnancy diabetes, insulin resistance, including in polyendocrine metabolic ovarian syndrome, obesity, and advanced maternal age of 35 and above at the time of conception.

There are several perinatal complications associated with GDM. Some of these include an increased risk of preeclampsia, fetal cardiomyopathy, and neonatal respiratory complications. GDM is also associated with several long-term complications, with mothers having up to a 60% lifetime risk of developing type 2 diabetes mellitus. Children born to mothers with obesity and GDM have one of the highest risks of developing childhood obesity, type 2 diabetes mellitus, metabolic syndrome, and hypertension. Some of the proposed mechanisms underlying this association are discussed below.

  • Epigenetics: In previous blogs, we discussed epigenetics and how it can alter gene expression through mechanisms such as DNA methylation, histone modification, and chromatin remodeling, ultimately increasing the risk of childhood obesity (read more here). Pre-pregnancy obesity is not only a risk factor for GDM but also an independent risk factor for the offspring’s future weight trajectory. Having one parent with obesity increases the odds of childhood obesity approximately threefold, while having two parents with obesity increases the odds approximately tenfold. In addition, maternal insulin resistance is a strong predictor of weight gain and adiposity during the first 12 months of life.
  • Cesarean births: Large-for-gestational-age newborns, which are more common among mothers with GDM, are at increased risk for delivery complications, including shoulder dystocia and cesarean birth. Recall that cesarean delivery has been associated with an increased risk of childhood obesity, potentially due to differences in early gut microbiota. Infants born by cesarean section are initially colonized with more skin-associated bacteria rather than the vaginal flora encountered during vaginal delivery. For example, lower levels of Bifidobacterium and higher levels of Staphylococcus aureus (a common bacteria found on the skin) have been associated with increased weight during early childhood. Recall that, in adults, obesity has also been associated with a reduction in Bacteroidetes and an increase in Firmicutes.
  • Antibiotics: Early exposure to antibiotics has been associated with an increased risk of obesity. Because a previous blog discussed the influence of childhood antibiotic exposure on future weight in greater detail (read more here), we won’t spend as much time on this topic. However, it is important to recognize that mothers with overweight or obesity are more likely to be prescribed antibiotics during pregnancy, with the highest rates observed among those undergoing a cesarean delivery.

Prevention of GDM is the primary goal. During preconception counseling, weight loss before pregnancy is beneficial and should be recommended for individuals with overweight or obesity. Not only can this reduce the risk of GDM and its associated complications, but it may also reduce the risk of obesity in the offspring through favorable epigenetic changes. Depending on the desired timing of pregnancy, metabolic and bariatric surgery (MBS) should be considered in eligible patients, as it has been associated with approximately a 50% reduction in the incidence of macrosomia (7.6% vs. 3.2%). In addition, an interesting study from Sweden demonstrated that children born after maternal MBS, compared with siblings born before surgery, had differences in DNA methylation involving genes related to insulin signaling, leptin, and glucose metabolism, further supporting a role for epigenetic programming.

In addition, lifestyle modifications have independent benefits beyond weight loss in preventing GDM. Throughout pregnancy, moderate-intensity exercise for 100–120 minutes per week, dietary modification, and maintaining recommended gestational weight gain goals (see blog here) reduced the risk of GDM by approximately 20% compared with standard care. In this trial, dietary modifications included increasing the intake of fruits, vegetables, and whole grains while reducing the consumption of red meat and high-fat dairy products. Interestingly, although metformin has been shown to reduce the development of type 2 diabetes mellitus in individuals with a history of GDM, it does not appear to prevent or reduce the risk of GDM during pregnancy.

Fortunately, for most patients, glycemic levels return to their pre-pregnancy baseline within approximately 2 weeks after delivery as the hormonal influences of the placenta resolve. However, these patients remain at increased risk of developing prediabetes and type 2 diabetes mellitus later in life and should therefore focus on risk-factor mitigation and undergo closer monitoring. Therefore, obtaining a history of GDM is an important component of a comprehensive obesity evaluation.

With that information, you should be well prepared for GDM-related questions on the exam. The diagnosis and management of GDM are generally beyond the scope of the exam, whereas prevention and the associations between GDM and obesity, especially the long-term effects on offspring, are high-yield concepts. For additional high-yield information, be sure to check out the related linked blogs.

Sample Question

A 31-year-old woman with obesity undergoes a routine oral glucose tolerance test at 26 weeks’ gestation, which confirms gestational diabetes mellitus. At 39 weeks, she delivers a large-for-gestational-age infant by cesarean section and plans to breastfeed. Which of the following findings is most associated with an increased risk of early childhood obesity in this infant?

 

A. Gastrointestinal colonization with Staphylococcus aureus

B. Requirement for general anesthesia during the cesarean delivery

C. Postoperative maternal wound infection requiring antibiotics

D. Early initiation of breastfeeding

E. Delayed umbilical cord clamping

 

Next Week: Liraglutide

Upcoming: Lipodystrophy and Special Populations with Obesity (Turner Syndrome, Achondroplasia, and Down Syndrome)

For more practice questions, check out the following:

  • Obesity Medicine Board Review Questions (2026): Q’s 5 and 34.
  • Obesity Medicine Practice Tests (2026): Q’s 168 and 337.

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