Gestational diabetes mellitus (GDM) is a condition characterized by hyperglycemia that is first diagnosed during pregnancy. This condition presents significant health risks for both the mother and the developing fetus. The methods for diagnosing GDM have been refined over time, reflecting advancements in our understanding of glucose metabolism and pregnancy, as well as the technologies available for glucose testing. Historically, diagnosis often involved a 2-step approach, combining a glucose challenge test with an oral glucose tolerance test (OGTT). More recently, the American Diabetes Association and other bodies have advocated for a 1-step approach using a 75-gram 2-hour OGTT. The adoption of newer diagnostic criteria has led to a notable increase in GDM prevalence, underscoring the critical need for effective screening and early intervention to minimize complications such as macrosomia, neonatal hypoglycemia, and potential long-term health consequences for both mother and child. Management strategies for GDM are also continuously evolving, encompassing dietary adjustments, lifestyle modifications, and, when necessary, pharmacological interventions.
This article aims to provide a comprehensive overview of GDM, focusing on current diagnostic procedures, risk factors, and evolving management strategies. It emphasizes the importance of early and accurate diagnosis to improve outcomes for both mothers and their infants. This resource is designed to help clinicians effectively identify at-risk individuals, apply recommended screening and diagnostic tools, and implement appropriate management plans in a collaborative, interprofessional setting. Such collaboration is vital to ensure holistic care, addressing both the immediate and long-term health implications of GDM for both mother and child.
Objectives:
- Identify key risk factors associated with gestational diabetes mellitus to facilitate timely diagnosis and intervention.
- Differentiate gestational diabetes mellitus from other forms of diabetes to ensure accurate diagnosis and appropriate treatment strategies.
- Select and implement evidence-based therapeutic interventions for gestational diabetes mellitus, tailored to individual patient needs and current best practices.
- Foster effective collaboration within an interprofessional healthcare team to provide comprehensive care for patients with gestational diabetes mellitus and ensure coordinated follow-up to manage ongoing health and prevent long-term complications.
Introduction
Gestational diabetes mellitus (GDM) is defined as hyperglycemia that is first detected during pregnancy. It is often categorized into diet-controlled GDM (class A1GDM) and GDM requiring pharmacological treatment for blood sugar management (class A2GDM).[1] Recognizing and diagnosing GDM is crucial because women with this condition have a significantly elevated risk of developing type 2 diabetes later in life. Furthermore, timely and effective management of GDM during pregnancy is proven to reduce adverse pregnancy outcomes. However, despite its importance, there remains some variability in the global consensus regarding the optimal diagnostic criteria for GDM and the ideal timing for screening during pregnancy.[2]
The approach to managing GDM has undergone considerable evolution, driven by historical concerns about high perinatal mortality rates among pregnant women with diabetes. A pivotal moment in GDM diagnosis came in 1964 with the groundbreaking research by O’Sullivan and Mahan, which established specific diagnostic criteria for GDM in the United States. Their criteria, based on a 100-gram 3-hour oral glucose tolerance test, were designed to pinpoint women at increased risk, aiming to link maternal hyperglycemia to adverse perinatal outcomes. Subsequent studies validated the significance of these diagnostic thresholds in predicting both immediate pregnancy complications and long-term health risks for mothers and their children.[1][3]
Since then, the refinement of GDM diagnostic criteria has been a continuous process, shaped by ongoing scientific research and evolving standards in maternal-fetal medicine. From the adoption of specific glucose thresholds by international organizations like the World Health Organization (WHO) to the endorsement of comprehensive criteria by the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) in 2013, GDM management strategies continue to adapt. These advancements underscore the complexity of GDM diagnosis and highlight the essential need for evidence-based guidelines to effectively mitigate risks for both mothers and infants. As diagnostic methodologies become increasingly precise, ongoing research is vital to further optimize maternal and perinatal outcomes while addressing the diverse healthcare needs of pregnant women worldwide.[1][3]
Etiology of Gestational Diabetes Mellitus
The primary cause of gestational diabetes mellitus is insulin resistance induced by placental hormones. While several hormones contribute, human placental lactogen is considered a key factor. This hormone, while increasing insulin resistance, also typically boosts insulin secretion and pancreatic β-cell proliferation in normal pregnancies to maintain stable maternal blood glucose levels. However, in women who develop GDM, underlying conditions or factors impair pancreatic β-cell function or delay their response, leading to insufficient insulin secretion and subsequent hyperglycemia. Maternal obesity, especially early in pregnancy, also significantly contributes to insulin resistance due to elevated levels of free fatty acids, which inhibit glucose uptake by maternal tissues and stimulate glucose production by the liver (hepatic gluconeogenesis).[3]
Genetic factors also play a role in the development of GDM. While genetic research in diabetes has largely focused on type 2 diabetes, studies have identified overlapping genetic abnormalities in GDM. Polymorphisms in genes such as MTNR1B, TCF7L2, HKDC1, GCKR, PPP1R3B, and IRS1, which are involved in insulin secretion, glucose metabolism, and insulin resistance in type 2 diabetes, have also been associated with GDM. These genetic links suggest shared underlying mechanisms in both conditions.[3]
Clinicians should also consider maturity-onset diabetes of the young (MODY), a monogenic form of diabetes that can be misdiagnosed as GDM. It is estimated that MODY accounts for up to 5% of GDM diagnoses. MODY should be suspected in pregnant women with a strong family history of diabetes who present with specific OGTT results: a fasting glucose level ≥ 5.5 mmol/L and a relatively small glucose increase from fasting to the 2-hour OGTT result (less than 4.6 mmol/L). Additionally, in women with a BMI under 25 kg/m², a fasting glucose level ≥ 100 mg/dL may also suggest MODY rather than GDM. Further information on MODY can be found in the StatPearls reference, “Maturity Onset Diabetes in the Young.”
Risk Factors for Gestational Diabetes
Several clinical risk factors are associated with an increased likelihood of developing gestational diabetes:
- Elevated body mass index (BMI) ≥25 kg/m², or ≥23 kg/m² for Asian Americans
- Low levels of physical activity
- Family history of diabetes mellitus in a first-degree relative
- High-risk ethnic background (e.g., African American, Hispanic/Latino, Native American, Asian American, Pacific Islander)
- History of:
- Previous GDM in earlier pregnancies
- Prior delivery of a newborn weighing ≥4000 g (macrosomia)
- Cardiovascular disease
- Pre-existing hypertension
- Low high-density lipoprotein cholesterol (HDL-C) levels (<35 mg/dL) and/or high triglyceride levels (>250 mg/dL)
- Polycystic ovary syndrome (PCOS)
- Hemoglobin A1c ≥5.7% prior to pregnancy
- Previous abnormal oral glucose tolerance test (OGTT)
- Clinical signs of insulin resistance, such as acanthosis nigricans [1]
Image alt text: Diagram illustrating risk factors for gestational diabetes, including obesity, family history of diabetes, advanced maternal age, and certain ethnicities.
Epidemiology of Gestational Diabetes Mellitus
Gestational diabetes mellitus is a prevalent pregnancy complication worldwide. The International Diabetes Federation estimates that globally, approximately 1 in 6 live births are affected by GDM.[3] In the United States, diabetes of any type complicates about 7% of pregnancies, with GDM accounting for 86% of these cases.[1] The prevalence of GDM in Europe is estimated to be around 10.9%.[4] These figures highlight the significant public health impact of GDM and the importance of effective screening and management strategies.
Pathophysiology of Gestational Diabetes Mellitus
Normal pregnancy is characterized by physiological increases in placental hormones, including growth hormone, corticotrophin-releasing hormone, human placental lactogen, prolactin, estrogen, and progesterone. These hormonal changes collectively lead to increased insulin resistance, particularly during the second and third trimesters. Human placental lactogen (hPL), structurally similar to growth hormone, plays a central role in these metabolic adaptations, ensuring adequate nutrient supply to the fetus. hPL alters insulin receptors, leading to molecular changes such as modifications in the beta-subunit of the insulin receptor, reduced tyrosine kinase phosphorylation, and changes in insulin receptor substrate-1 and phosphatidylinositol 3-kinase pathways. These changes result in decreased glucose uptake by peripheral tissues. While insulin resistance increases maternal blood glucose levels and free fatty acids, ensuring glucose availability for fetal growth, normal pregnancy also involves a compensatory increase in maternal insulin secretion to maintain normal blood sugar levels (euglycemia). These physiological processes are the reason why GDM screening is typically performed during the second and third trimesters.[3]
In GDM, the pathophysiology mirrors that of type 2 diabetes, primarily driven by increased insulin resistance coupled with insufficient insulin secretion. Maternal pancreatic β-cell dysfunction is the key factor that prevents adequate compensation for the pregnancy-induced insulin resistance. This dysfunction leads to reduced insulin secretion, ultimately resulting in elevated maternal glucose levels. This, in turn, causes decreased glucose uptake by tissues, increased hepatic glucose production, and maternal hyperglycemia. Elevated serum triglyceride levels may also contribute to β-cell damage (lipotoxicity), further impairing insulin secretion.[3] The elevated maternal glucose readily crosses the placenta, causing fetal hyperglycemia. In response, the fetal pancreas increases insulin production. Insulin’s anabolic effects then drive accelerated fetal tissue growth, potentially leading to macrosomia.[5]
History and Physical Examination in GDM Diagnosis
Gestational diabetes mellitus is typically first identified through routine screening tests during pregnancy. Therefore, obtaining a thorough medical history, including past obstetric outcomes and family history of type 2 diabetes, is crucial for initial GDM risk assessment. Clinical presentations of GDM can vary, but disproportionate weight gain, obesity, and elevated BMI are common suggestive features.[1]
The American College of Obstetricians and Gynecologists (ACOG) recommends early targeted screening for type 2 diabetes at the first prenatal visit for women with a BMI of 30 kg/m² or higher and at least one additional risk factor. This early screening may involve a 75-g or 50-g oral glucose tolerance test. Risk factors prompting early screening include:
- History of gestational diabetes mellitus in prior pregnancies
- Hemoglobin A1c ≥5.7% on previous testing
- First-degree relative with diabetes
- High-risk race or ethnicity (e.g., African American, Hispanic/Latino, Native American, Asian American, Pacific Islander)
- History of cardiovascular disease
- Hypertension
- Low HDL cholesterol levels (<35 mg/dL) or high triglyceride levels (>250 mg/dL)
- Polycystic ovary syndrome (PCOS)
- Physical inactivity [6][1]
However, research indicates that the strongest predictors for GDM risk are family history of diabetes, previous GDM, Southeast Asian ethnicity, parity, and high BMI. Ethnic and racial disparities in GDM risk factors should be carefully considered in screening strategies.[7] Furthermore, some recent studies suggest that universal early GDM screening may not prevent adverse outcomes and might even lead to worse outcomes in certain populations. These findings highlight the complexities in GDM pathogenesis and management, suggesting that the effectiveness of routine early GDM screening is still under debate and requires further investigation.[8][9]
Evaluation and Diagnosis of Gestational Diabetes Mellitus
Gestational Diabetes Screening and Diagnostic Testing
Routine laboratory screening for gestational diabetes is typically performed during the second trimester, between 24 and 28 weeks of gestation, to allow sufficient time for interventions. This is recommended by ACOG, USPSTF, and other professional organizations for all pregnant women. However, specific screening methods and diagnostic thresholds vary among different guidelines.[1] The IADPSG and the American Diabetes Association (ADA) favor a 1-step approach for GDM diagnosis, using a 2-hour 75-g OGTT. The primary advantage of the 1-step approach is that it combines screening and diagnosis in a single visit, streamlining the process for both patients and healthcare providers. However, it requires fasting and a time commitment of approximately 2 hours for the test procedure.[10]
Image alt text: Infographic comparing the 1-step and 2-step approaches for gestational diabetes diagnosis, highlighting the glucose tolerance test and glucose challenge test.
Conversely, the 2-step approach, recommended by ACOG, begins with a non-fasting 1-hour 50-g glucose challenge test (GCT). This initial test is easily integrated into routine prenatal visits and is simpler to administer. Most women pass the GCT and do not require further testing. However, about 20% of women will have an elevated GCT result and proceed to a 3-hour fasting diagnostic OGTT to confirm a GDM diagnosis. This two-step process aims to reduce the number of women needing the more complex diagnostic test. Different glucose cut-off values are used to define an abnormal GCT result, including ≥135 mg/dL (7.5 mmol/L), ≥130 mg/dL (7.22 mmol/L), and ≥140 mg/dL (7.8 mmol/L). As studies have not conclusively identified an optimal cut-off, clinicians should select a threshold based on the local prevalence of GDM risk factors and their preference for test sensitivity and specificity.[10]
For women who screen positive on the 50-g GCT, a diagnostic 100-g 3-hour OGTT is performed.[1] The diagnostic thresholds for the 3-hour OGTT are:
- Fasting: ≥95 mg/dL
- 1-hour: ≥180 mg/dL
- 2-hour: ≥155 mg/dL
- 3-hour: ≥140 mg/dL [1]
A diagnosis of gestational diabetes is confirmed if two or more of these glucose values are met or exceeded.[1]
A key difference between the 1-step and 2-step approaches lies in their diagnostic thresholds. The 1-step method employs stricter criteria, identifying women with milder degrees of hyperglycemia as having GDM. This approach aims to identify GDM earlier, potentially enabling earlier interventions and improved pregnancy outcomes. However, the lower thresholds in the 1-step approach may result in a higher GDM prevalence compared to the 2-step method. Clinical trials have not shown significant differences in perinatal outcomes between these two diagnostic strategies. Consequently, both 1-step and 2-step methods are considered acceptable for GDM diagnosis.[10][2]
Postpartum Gestational Diabetes Evaluation
Postpartum glucose evaluation is recommended for women with GDM, typically 24 to 72 hours after delivery. After placental removal, insulin resistance usually improves, and insulin or oral hypoglycemic medications, if used, can often be reduced or discontinued.[1][11][12] While GDM often resolves after pregnancy, a significant proportion of women with GDM, up to one-third, will develop diabetes or impaired glucose metabolism later in life. Studies indicate that between 15% and 70% of women with a history of GDM may progress to diabetes, predominantly type 2 diabetes. Women with prior GDM have a significantly higher risk, up to seven times greater, of developing type 2 diabetes compared to women without a history of GDM. Due to these substantial risks, guidelines recommend postpartum screening for all women who have had GDM, ideally between 4 to 12 weeks postpartum.[1]
Postpartum screening can be performed using a fasting plasma glucose test or a 75-g 2-hour OGTT. While the fasting plasma glucose test is logistically simpler, the OGTT is generally preferred as it can detect both impaired fasting glucose and impaired glucose tolerance, providing a more comprehensive assessment of postpartum glucose status.[1] Recommended management based on postpartum screening results includes:
- Diabetes: Fasting plasma glucose >125 mg/dL or 2-hour OGTT glucose >199 mg/dL. Initiate or refer for diabetes management.
- Impaired Fasting Glucose or Impaired Glucose Tolerance: Fasting plasma glucose 100 to 125 mg/dL or 2-hour OGTT glucose 140 to 199 mg/dL. Recommend lifestyle modifications including dietary changes and increased physical activity for weight loss. Refer for nutritional counseling as needed. Consider metformin therapy, especially if both fasting glucose and glucose tolerance are impaired. Annual screening for diabetes is recommended using hemoglobin A1c, fasting plasma glucose, or 75-g OGTT with non-pregnancy diagnostic thresholds.[13]
- Normal Findings: Encourage maintenance of a healthy lifestyle and routine health check-ups.
Early detection of impaired glucose metabolism through postpartum screening allows for timely preventive interventions, such as lifestyle modifications, and early treatment for those diagnosed with diabetes. Despite these recommendations, postpartum testing rates remain suboptimal, with only 23% to 58% of women undergoing recommended postpartum evaluation. This gap between guideline recommendations and clinical practice highlights the need for improved patient education and increased clinician engagement to ensure appropriate postpartum follow-up for women with a history of GDM.[7][3]
Treatment and Management of Gestational Diabetes Mellitus
Non-pharmacological Therapies
Initial management of gestational diabetes mellitus typically involves non-pharmacological approaches, including lifestyle modifications such as increased physical activity, dietary adjustments, and regular self-monitoring of blood glucose. The recommended level of physical activity for women with GDM is at least 30 minutes of moderate-intensity aerobic exercise on most days of the week, totaling a minimum of 150 minutes per week. Postprandial exercise, performed shortly after meals, is often particularly beneficial as it can help improve glucose control for up to 3 hours after eating.[2]
Dietary Modifications and Gestational Weight Management
Nutritional counseling by a registered dietitian is a cornerstone of GDM management, as recommended by both the ADA and ACOG. Individualized meal plans should be developed based on the patient’s pre-pregnancy BMI and current gestational weight gain goals to ensure adequate caloric intake while preventing excessive weight gain. General dietary recommendations include consuming three small to moderate-sized meals and two to three snacks daily, emphasizing whole-grain carbohydrates, lean protein sources, and unsaturated fats. It is often advised to reduce carbohydrate intake at breakfast due to increased carbohydrate intolerance in the morning. While ACOG recommends a diet lower in carbohydrates, the optimal macronutrient ratio for women with GDM is still under investigation. Some studies suggest that combining carbohydrates with lean proteins can help mitigate postprandial hyperglycemia. To prevent nocturnal ketosis, which can potentially impact fetal neurodevelopment, a bedtime snack is often recommended.[2]
Gestational weight gain significantly influences pregnancies complicated by GDM. Maternal obesity and excessive weight gain are linked to an increased risk of fetal macrosomia, gestational diabetes itself, gestational hypertension, preeclampsia, and Cesarean delivery.[14][3] Obese pregnant women also face higher risks of antepartum complications such as cardiac dysfunction, proteinuria, nonalcoholic fatty liver disease, and sleep apnea, as well as intrapartum complications including endometritis, failed labor induction, venous thrombosis, and wound complications. Macrosomia, more common in obese pregnancies, is associated with maternal complications like prolonged labor, uterine rupture, genital tract lacerations, and postpartum hemorrhage, and neonatal complications such as shoulder dystocia, clavicular fractures, brachial plexus injuries, and nerve palsies. A meta-analysis highlighted that the highest risk for adverse outcomes occurs in women with a BMI over 40 and high gestational weight gain.[15] Gestational weight gain recommendations are tailored to pre-pregnancy BMI categories to optimize maternal and fetal health.
