Approach

The main goal of treatment is good glycemic control during pregnancy to reduce the risk of pregnancy complications, particularly macrosomia with its attendant risks.[67] 

Treatment appears to lower the risk of shoulder dystocia, preeclampsia and hypertensive disorders in pregnancy, but evidence is insufficient to support benefit on other outcomes such as neonatal metabolic complications (e.g., hypoglycemia, hypocalcemia) and maternal C-section.[67][68]​​​​​ There is a continuous, dose-dependent association between hyperglycemia and adverse pregnancy outcomes.[69]​ In one study of women treated for mild gestational diabetes mellitus (GDM), higher median fasting glucose during the first 2 weeks of diet therapy was associated with increased neonatal fat mass and elevated C-peptide; during the last 2 weeks before delivery it was associated with macrosomia, large-for-gestational age fetus, and elevated C-peptide.[70]

Although it is widely accepted that GDM should be treated, the precise glycemic targets remain unclear and there is international variation in target recommendations, which are based primarily on consensus. A 2023 Cochrane systematic review found limited evidence for the benefit of different intensities of glycemic targets for women with GDM to minimize adverse effects on maternal and infant health, and concluded that further high-quality trials are needed.[71] [ Cochrane Clinical Answers logo ]

Lifestyle interventions, including education, healthy eating, physical activity, and self-monitoring of blood sugar levels, are the first-line treatment for women with GDM.[1][72]​ A 2018 Cochrane review found that lifestyle interventions resulted in fewer babies being born large for gestational age, although these approaches were also associated with a higher risk of labor induction.[73] [ Cochrane Clinical Answers logo ] ​​ 

Approximately 1 in 4 individuals will require pharmacotherapy in addition in order to achieve glycemic targets.[69]​ Insulin is the preferred medication for treating hyperglycemia.[1]​ 

Glucose monitoring

Self-monitoring of blood glucose is initiated to assess fasting and postprandial glycemia and guide therapy.[1]​ Target blood glucose levels, per the ADA, AACE, and the American College of Obstetricians and Gynecologists (ACOG), for GDM are:[1][42][51][63]

  • Fasting (preprandial) <95 mg/dL (<5.3 mmol/L) and either

  • 1-hour postprandial <140 mg/dL (<7.8 mmol/L) or

  • 2-hour postprandial <120 mg/dL (<6.7 mmol/L)

These goals have been aligned with the recommendations for patients with type 1 and type 2 diabetes.

ACOG guidelines note that there is insufficient evidence to define the optimal frequency of blood glucose testing in women with GDM; however, based on the available data, the general recommendation is for glucose monitoring four times a day, once fasting and again usually 2 hours after each meal.[51] In patients whose glucose levels are well controlled by diet, the frequency of monitoring may be modified depending on gestational age, overall concerns for concordance, and likely need for future adjustments in care. However, it is unusual to recommend obtaining fewer than two measurements per day.[51]

Continuous glucose monitoring (CGM) enables determination of peak postprandial glucose levels, mean glucose level, episodes of nocturnal hуреrglyϲеmiа, and percent time in range (TIR) for a 24-hour period. It is widely recommended for pregnancies complicated by type 1 diabetes due to compelling data showing even 4% to 7% improvements in TIR can result in an approximate 50% decrease in large for gestational age infants and NICU admissions; however, the data for type 2 diabetes and GDM are more limited and conflicting and not sufficient to recommend TIR or mean glucose targets specific to these conditions.[1][74][75]​​​​[76]​ The ADA notes that CGM can help to achieve HbA1c targets in pregnancy when used in addition to pre- and postprandial blood glucose monitoring. However, it concludes that data are insufficient to recommend CGM for all patients with GDM and the decision to use CGM should be individualized.[1]

Diet and exercise

Medical nutrition therapy is central to the control of GDM, and most women are adequately treated with diet alone. There is insufficient evidence to support one dietary approach over another.[77][78]​​ All women should be referred to a registered dietitian, if available.[1]​ Nutrition counseling should endorse a balance of macronutrients including nutrient-dense fruits, vegetables, legumes, whole grains, and healthy fats with omega-3 fatty acids that include nuts and seeds and fish in the eating pattern.[1]​​[23]​ The nutrition plan should emphasize monounsaturated and polyunsaturated fats while limiting saturated fats and avoiding trans fats. Processed foods, fatty red meat, and sweetened foods and beverages should be limited.[1]

There is no definitive research that identifies a specific optimal calorie intake for people with GDM or suggests that their calorie needs are different from those of pregnant individuals without GDM.[1] The ADA advises that the food plan should provide adequate calorie intake to promote fetal/neonatal and maternal health, achieve glycemic goals, and promote appropriate weight gain, according to the 2009 National Academy of Medicine recommendations for weight gain during pregnancy.[1][33]​​​

As is true for all nutrition therapy in people with diabetes, the amount and type of carbohydrate will impact glucose levels. Promoting higher-quality, nutrient-dense carbohydrates results in controlled fasting/postprandial glucose, lower free fatty acids, improved insulin action, and vascular benefits and may reduce excess infant adiposity.[1] Complex carbohydrates are recommended over simple carbohydrates because they are digested more slowly, are less likely to produce significant postprandial hyperglycemia, and potentially reduce insulin resistance.[51] A meta-analysis of dietary interventions concluded that a low-glycemic-index diet was associated with a less frequent need for insulin and lower infant birth weights than calorie-restricted diets, low carbohydrate diets, or other diets.[79] The ADA warns that individuals who substitute fat for carbohydrates may unintentionally enhance lipolysis, promote elevated free fatty acids, and worsen maternal insulin resistance.[1] Fasting urine ketone testing may be useful to identify those who are severely restricting carbohydrates to manage blood glucose.[1]

Moderate-intensity exercise (e.g., brisk walking, easy jogging, or swimming) during pregnancy is recommended and has been associated with lowering of maternal glucose levels in some but not all studies.[51][80]​​​ ACOG guidelines comment that there are few published exercise trials in women with GDM, and most of these trials have small sample sizes; however, they do appear to show improvement in glucose levels.[51] They recommend that exercise plans should mirror diabetes care in general, and women with GDM should aim for 30 minutes of moderate-intensity aerobic exercise at least 5 days a week or a minimum of 150 minutes per week. Simple exercise such as walking for 10-15 minutes after each meal can lead to improved glycemic control and is commonly recommended.[51]

A small randomized controlled trial of mindful eating and yoga suggested the potential for alternative strategies to improve outcomes in GDM as well; however, further studies are needed to establish the use of complementary therapies for the treatment of GDM.[81]

Insulin therapy

Pharmacologic treatment is recommended when target glucose levels cannot be consistently achieved through nutrition therapy and exercise.[51] Insulin has historically been considered the standard therapy for GDM management in cases refractory to nutrition therapy and exercise and this has continued to be reinforced by the ADA.[1] Insulin management in pregnancy is often complex and commonly requires frequent dose titration; the ADA recommends referral to a specialized center offering team-based care for women prescribed insulin in pregnancy, if this is available.[1] Both multiple daily insulin injections and continuous subcutaneous insulin infusion are reasonable delivery strategies, and neither has been shown to be superior to the other during pregnancy.[1]

Insulin can achieve tight metabolic control and has traditionally been added to nutrition therapy if fasting blood glucose levels are consistently greater than or equal to 95 mg/dL, if 1-hour levels consistently are greater than or equal to 140 mg/dL, or if 2-hour levels consistently are greater than or equal to 120 mg/dL.[51] These thresholds have largely been extrapolated from recommendations for managing pregnancy in women with preexisting diabetes.[51] A systematic review found no conclusive evidence for a specific threshold value at which medical therapy should be started.[82]​ A study of women with GDM treated with dietary therapy for 4 weeks before initiating insulin found that most women who achieved good control with diet did so within 2 weeks and had baseline fasting plasma glucose levels of <95 mg/dL.[83] Accordingly, the authors suggested that patients with a fasting plasma glucose <95 mg/dL attempt dietary therapy for at least 2 weeks before starting insulin, whereas insulin should be started at diagnosis or within a week of failed dietary therapy in patients with fasting glucose levels >95 mg/dL.[83] Such severe elevations imply the need for aggressive therapy with prompt initiation of insulin. 

The physiology of pregnancy necessitates frequent, highly individualized, titration of insulin to match changing requirements and underscores the importance of daily and frequent blood glucose monitoring.[1] Requirements increase throughout pregnancy and average 0.8 units/kg/day in the first trimester, 1 unit/kg/day in the second trimester, and 1.2 units/kg/day in the third trimester, before dropping dramatically after delivery.[1][84]​​ The daily dosage should be divided with a regimen of multiple injections using long-acting or intermediate-acting insulin in combination with short-acting insulin. However, if there are only isolated abnormal values at a specific time of day, focusing the insulin regimen to correct the specific hyperglycemia is preferred.[51]​

  • For isolated fasting hyperglycemia, a useful approach is to use intermediate-acting insulin (e.g., insulin NPH [Neutral Protamine Hagedorn]) or long-acting insulin (e.g., insulin glargine) at bedtime and then adjust dose to achieve fasting blood glucose <95 mg/dL (<5.3 mmol/L).[51][85]​​

  • To address postprandial hyperglycemia, one approach is to use intermediate-acting or long-acting insulin once or twice daily, with short-acting prandial insulin (e.g., insulin lispro, insulin aspart) titrated to meet glycemic targets.[42][85]​​

Human and analog insulins are the most extensively studied in pregnancy. When used at therapeutic doses, they do not cross the placenta and are generally considered safe.

  • For long-acting and intermediate-acting insulin, NPH insulin has been the mainstay, but more recently long-acting insulin glargine has been used.[51] Insulin detemir was frequently used instead of insulin glargine, especially in Europe, but production of insulin detemir has been discontinued. Although there is more limited experience with long-acting insulin analogs, there is no evidence of adverse maternal or fetal outcomes with these agents.​[1]​​[85][86][87][88]​​ 

  • For short-acting insulin, insulin lispro and insulin aspart should be used preferentially over regular human insulin because both have a more rapid onset of action, enabling the patient to administer their insulin right at the time of a meal rather than 10-15 minutes before an anticipated meal. This provides better glycemic control and helps avoid hypoglycemic episodes from errors in timing.[51]​ Evidence suggests that they are safe in pregnancy.[23][89]

Antepartum fetal assessment

The evidence for different obstetric and surveillance strategies for pregnancies complicated by GDM remains scarce. A detailed ultrasound scan at 18-20 weeks of gestation (for identification of structural malformations) is recommended by most professional bodies for all pregnancies.[78] 

Ultrasound-assessed abdominal circumference and estimated fetal weight may be indirect indicators of glycemic control in patients with GDM; however, fetal growth is driven by multiple factors.[78] As increasing fetal size is associated with increased risk of shoulder dystocia and birth trauma, assessment of fetal size, either clinically or with ultrasound, may also be useful in planning delivery route. It should be noted that ultrasound overestimates the prevalence of large-for-gestational-age fetal weight in women with GDM.[90] Although it is reasonable to offer cesarean delivery to reduce the risk for shoulder dystocia if the estimated fetal weight is >4500 g, the estimation of fetal weight regardless of modality is imprecise, and therefore counseling should be individualized; fetal macrosomia is not itself an indication for delivery.[91] It has been estimated that up to 588 cesarean deliveries would be needed to prevent a single case of permanent brachial plexus palsy for an estimated fetal weight of 4500 g, and up to 962 cesarean deliveries would be needed for an estimated fetal weight of 4000 g.[51]

ACOG guidelines advise that fetal surveillance in women with poorly controlled or medication-requiring GDM without other morbidities is usually initiated at 32 weeks of gestation.[51] If other factors associated with increased risk of adverse pregnancy outcome are present, it may be reasonable to start surveillance earlier in pregnancy.[51] There is no consensus regarding antepartum fetal testing among women with well-controlled GDM who are not pharmacologically treated; studies have not specifically demonstrated an increase in stillbirth with GDM well-controlled without medication before 40 weeks of gestation.[51] If testing is to be undertaken in such patients, it is generally started later than in women who require antihyperglycemic medication.[51] The specific antepartum test and frequency of testing may be chosen according to local practice; however, because polyhydramnios can result from fetal hyperglycemia, it is common for clinicians to use testing that incorporates serial measures of amniotic fluid.[51] For women with poor GDM control and those requiring insulin therapy, more intensive fetal monitoring with nonstress tests or biophysical profile assessments once or twice weekly is indicated to reduce the risk for stillbirth.[23][92]

Timing of delivery

Women with GDM with good glycemic control and no other complications are commonly managed expectantly until term.[51] In most cases, women with good glycemic control who are receiving medical therapy do not require delivery before 39 weeks of gestation.[51][93]​​ Expert opinion has supported earlier delivery for women with poorly controlled GDM; however, clear guidance about the degree of glycemic control that should indicate earlier delivery is lacking, and the recommendations about timing of delivery lack specific guidance as well. In light of this, decisions about timing of delivery should be individualized.[93] Consideration of timing should incorporate tradeoffs between the risks of prematurity and the ongoing risks of stillbirth. In such a setting, delivery between 37+0 weeks and 38+6 weeks of gestation may be justified. Delivery in the late preterm period from 34+0 weeks to 36+6 weeks of gestation should be reserved for those women for whom in-hospital attempts to improve glycemic control are unsuccessful or who have abnormal antepartum fetal testing.[51]

Intrapartum glycemic control

Intrapartum glycemic monitoring is widely recommended in women with GDM requiring insulin.[94] There are no large randomized controlled trials of intrapartum glycemic control to lessen the risk of neonatal hypoglycemia; however, based on limited evidence, avoiding maternal hyperglycemia during labor in women with GDM is recommended and may require intravenous insulin to achieve.[95]

The Joint British Diabetes Societies (JBDS) for Inpatient Care Group recommends that all women with diabetes of any type should have hourly blood glucose (capillary, flash, or CGM) monitoring in established labor or from the morning of elective cesarean section.[66]​ In addition, it adds that if general anesthesia is used, monitoring should be every 30 minutes until the woman is fully conscious.[66]​​​

In the UK, it is recommended that glucose levels are maintained in either the target range advocated in the NICE guidelines (4.0 to 7.0 mmol/L [72 to 126 mg/dL]) or in the more liberal range of 5.0 to 8.0 mmol/L (90 to 144 mg/dL) due to lack of randomized controlled trial evidence for either target.[19][66]​​​ Some women with GDM may require variable rate intravenous insulin infusion to achieve target glucose levels.[66]​​

Immediately after placental delivery, a large reduction in insulin requirement occurs, and this must be anticipated to avoid hypoglycemia. Initial postpartum insulin needs are generally as low as, or lower than, prepregnancy requirements.

General

All women should continue taking folic acid (started before conception) to reduce the risk of neural tube defects.​[1]​​ Some experts recommend higher doses of folic acid for women with high BMI or with diabetes; however, there are no data to support a specific dose beyond 400 micrograms daily for women without a history of fetal neural tube defects.

In the long term, therapeutic lifestyle changes such as diet, exercise, and smoking cessation are important to reduce the risk of cardiovascular disease.[96]

Role of oral antihyperglycemic agents

Oral antihyperglycemic agents are not recommended as first-line therapies for GDM by the American Diabetes Association (ADA).[1] The two oral antihyperglycemic agents that have data to support their use in pregnancy, metformin and the sulfonylurea glyburide, are known to cross the placenta and/or lack long-term safety data in offspring.[1] Their role, therefore, remains a matter of debate; however, in practice they are widely used in some settings because of multiple factors including affordability and acceptability.[97]​ See Emerging treatments for a further discussion of the role of oral antihyperglycemic agents in the management of GDM.

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