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Apr.11.2022

Gestational Diabetes

Synopsis

Key Points

  • Gestational diabetes is any degree of glucose intolerance with onset or first recognition during pregnancy
  • Diagnosis is usually made with oral glucose tolerance test
  • Mainstay of treatment consists of lifestyle changes and, when necessary, oral hypoglycemic agents or insulin to achieve specified glycemic targets
  • Treatment of gestational diabetes can reduce the rate of adverse pregnancy outcomes,r1r2 including macrosomia, fetal adiposity, preeclampsia, and gestational hypertension
  • Patients with gestational diabetes are at higher lifetime risk for development of postpartum type 2 diabetesr3
  • Treatment of gestational diabetes is associated with improved health outcomes r4

Urgent Action

  • Patients found to have severe hyperglycemia (ie, glucose levels indicative of overt diabetes) should be treated with insulin immediately

Pitfalls

  • Hemoglobin A1C target in pregnancy is less than 6%r5 but should be pursued only if it can be achieved without significant hypoglycemia

Terminology

Clinical Clarification

  • Gestational diabetes (gestational diabetes mellitus) is any degree of glucose intolerance with onset or first recognition during pregnancy: diagnosis is typically applied to patients meeting criteria for diagnosis when tested between 24 and 28 weeks of pregnancy r5r6
  • Patients who are diagnosed with diabetes at an early prenatal visit using standard diagnostic criteria are diagnosed with diabetes complicating pregnancy (this is usually type 2 diabetes) r6
  • Diagnostic criteria are based on results of oral glucose tolerance test; recommended diagnostic thresholds vary by professional society
    • Defining criteria of International Association of the Diabetes and Pregnancy Study Groupsr7r8 are used internationally and are endorsed by WHO,r9American Diabetes Associationr6, and Endocrine Societyr10
    • Defining criteria of American College of Obstetricians and Gynecologistsr11 and NIHr12 are used primarily in the United States

Classification

  • Pregnant patients with either gestational or preexisting diabetes are categorized according to the White classification: r13
    • Class A1: diabetes diagnosed during pregnancy and controlled by diet
    • Class A2: diabetes diagnosed during pregnancy and requiring medication
    • Class B: insulin-requiring diabetes diagnosed before pregnancy when patient is older than 20 years, which lasts fewer than 10 years
    • Class C: insulin-requiring diabetes diagnosed before pregnancy when patient is aged 10 to 19 years, which lasts 10 to 19 years
    • Class D: diabetes diagnosed with 1 of the following criteria: patient is older than 10 years, diabetes lasts more than 20 years, or diabetes is associated with hypertension or background retinopathy
    • Class F: diabetes with renal disease
    • Class H: diabetes with coronary artery disease
    • Class R: diabetes with proliferative retinopathy
    • Class T: diabetes with renal transplant

Diagnosis

Clinical Presentation

History

  • Typically asymptomatic and detected with screening tests c1
  • More severe hyperglycemia (at glucose levels that usually occur with overt diabetes) may cause the following symptoms:
    • Polydipsia c2
    • Polyuria c3
    • Polyphagia c4

Physical examination

  • Gravid uterus; otherwise unremarkable c5

Causes and Risk Factors

Causes

  • Insulin resistance progressively increases throughout gestation c6
  • Hyperglycemia develops when insulin resistance exceeds the compensatory insulin secretory capacity of pancreatic β-cells to maintain normoglycemia r14

Risk factors and/or associations

Age
  • More common in patients older than 25 years c7
Genetics
  • Polygenic influences contribute to risk r15r16c8
    • Increased risk of gestational diabetes in those with variants in TCF7L2, ABCC8, HKDC1, and BACE2 genes r15r17c9c10c11c12
  • Maternal history of gestational diabetes or family history of type 2 diabetes imparts strong risk c13c14
Ethnicity/race
  • Higher rates of gestational diabetes are found in the following populations: r18
    • African American c15
    • Hispanic c16
    • Native American c17
    • Asian c18
Other risk factors/associations
  • Overweight or obesityr19 (BMI greater than 25 kg/m²) c19c20
  • Personal history of glucose intolerance or prior gestational diabetes c21c22
  • Family history of gestational or type 2 diabetes c23
  • Polycystic ovary syndrome c24
  • Acanthosis nigricans r20c25
  • Twin gestation c26
  • Hypertension c27
  • Long-term corticosteroid use c28
  • Previous birth of infant weighing more than 4000 g or with shoulder dystocia c29c30
  • Unexplained perinatal loss or malformation c31c32

Diagnostic Procedures

Primary diagnostic tools

  • Routine screening for gestational diabetes is performed in all pregnant patients at 24 to 28 weeks of gestation
    • Consensus has not been reached regarding optimal strategy; either of the following approaches is acceptable: r6r21
      • Older and most widely used strategy in North America consists of 2 steps r11r20r22
        • Step 1: perform 1-hour 50-g oral glucose challenge test in all patients at 24 to 28 weeks of gestation
        • Step 2: if initial result is abnormal, perform 3-hour 100-g oral glucose tolerance test (2-hour 75-g test in Canada)r22
      • Alternative 1-step strategy is recommended by the American Diabetes Association and has been adopted internationally r6r8r10
        • Perform 75-g oral glucose tolerance test in all patients at 24 to 28 weeks of gestation
          • This method may be associated with better perinatal outcomes compared with 2-step approach r23
  • Early pregnancy screening for diabetes may be considered in patients at high risk for overt diabetes
    • Screening at initial prenatal tests for patients is as for nonpregnant patients (2-hour 75-g oral glucose tolerance test, fasting blood glucose, and/or hemoglobin A1C test) r6r11r20
      • Consider in pregnant patients of any age who are overweight (BMI of 25 kg/m² or higher, or 23 kg/m² or higher in Asian Americans) and have 1 or more additional risk factors, such as: r6r11
        • First-degree relative with diabetes
        • High-risk race or ethnicity (eg, African American, Hispanic, Native American, Pacific Islander, Asian American)
        • History of cardiovascular disease
        • Hypertension (blood pressure 140/90 mm Hg or higher or currently on therapy for hypertension)
        • Dyslipidemia (HDL cholesterol level less than 35 mg/dL and/or triglyceride level more than 250 mg/dL)
        • Polycystic ovary syndrome
        • Physical inactivity
        • Conditions associated with insulin resistance (eg, metabolic syndrome, nonalcoholic fatty liver disease, acanthosis nigricans)
        • Those who have previously given birth to an infant weighing more than 4000 g
        • Gestational diabetes in a previous pregnancy
        • Known impaired glucose metabolism
      • If glucose levels meet the criteria for diabetes as established for nonpregnant adults, the diagnosis is overt diabetes and not gestational diabetes r5r8
      • If results are not diagnostic of diabetes, test again at 24 to 28 weeks of gestation r8r22

Laboratory

  • Fasting plasma glucose or serum glucose test r8c33
    • Diagnostic of gestational diabetes: 92 to 125 mg/dL
    • Diagnostic of overt diabetes: 126 mg/dL or higher (same reference limit as general population) r6
  • Random plasma glucose or serum glucose test c34
    • Diagnostic of overt diabetes: glucose of 200 mg/dL or higher (same reference limit as general population) r6
  • Hemoglobin A1C test c35
    • Not recommended for diagnosis of gestational diabetes
    • May be used in lieu of plasma or serum glucose levels to diagnose overt diabetes; however, owing to increased RBC turnover, hemoglobin A1C level is usually lower in pregnant patients than in nonpregnant patients (reference ranges differ) r6
    • Diagnostic of overt diabetes: 6.5% or higher r6
    • Early pregnancy levels between 5.7% and 6.4% may predict subsequent development of gestational diabetes r24
  • Oral glucose tolerance test c36
    • 2-hour 75-g oral glucose tolerance test (1-step testing strategy) r6
      • Perform at 24 to 28 weeks on all patients not previously diagnosed with gestational diabetes
      • Perform test on morning after patient completes both an overnight fast of at least 8 hours
      • Blood glucose is measured while fasting and at 1 and 2 hours after oral glucose challenge
      • Diagnostic of gestational diabetes r6
        • Fasting glucose of 92 mg/dL or higher
        • 1-hour postprandial glucose level of 180 mg/dL or higher
        • 2-hour postprandial glucose level of 153 mg/dL or higher
    • 1-hour 50-g oral glucose tolerance test, followed by 3-hour 100-g glucose tolerance test, if indicated (2-step testing strategy)
      • Perform at 24 to 28 weeks on all patients not previously diagnosed with diabetes
        • 1-hour 50-g oral glucose tolerance test c37
          • First step in 2-step strategy and can be performed without fasting; blood glucose is measured at 1 hour after oral glucose challenge
          • If 1 hour after glucose challenge test glucose level is, depending on criteria used, 130 mg/dL, 135 mg/dL, 140 mg/dL, or higher, proceed to step 2 (3-hour 100-g glucose tolerance test after fasting) r6r11
        • 3-hour 100-g glucose tolerance test
          • Second step in 2-step strategy; perform in patients whose 1-hour postprandial glucose level is, depending on criteria used, 130 mg/dL, 135 mg/dL, 140 mg/dL, or higher
          • Perform test on morning after patient completes both an overnight fast of at least 8 hours
          • Gestational diabetes may be diagnosed using one of the following diagnostic criteria:
            • Carpenter and Coustan criteria (recommended by American Diabetes Association and American College of Obstetricians and Gynecologists) r6r11
              • Glucose at 0 hour (fasting): 95 mg/dL
              • Glucose level at 1 hour: 180 mg/dL or higher
              • Glucose level at 2 hours: 155 mg/dL or higher
              • Glucose level at 3 hours: 140 mg/dL or higher
            • National Diabetes Data Group criteria (recommended by American College of Obstetricians and Gynecologists) r11
              • Glucose at 0 hour (fasting): 105 mg/dL
              • Glucose level at 1 hour: 190 mg/dL or higher
              • Glucose level at 2 hours: 165 mg/dL or higher
              • Glucose level at 3 hours: 145 mg/dL or higher
            • American Diabetes Association bases diagnosis on 2 or more of the abnormal results; however, American College of Obstetricians and Gynecologists allows for use of a single elevated result r6r11

Imaging

  • Fetal ultrasonography
    • For patients in whom pregestational diabetes is suspected, begin fetal ultrasonographic surveillance in first trimester to monitor for congenital abnormalities c38
    • For patients with gestational diabetes, perform fetal ultrasonography between 28 and 36 weeks of gestation to estimate fetal weight and size c39
    • Information about fetal size is useful to identify any need for more intensive metabolic management,r25 scheduled cesarean delivery, or early induction of labor
      • Fetal abdominal circumference above 75th percentile is indicative of fetal overgrowth

Differential Diagnosis

Most common

  • Pregestational type 1 or type 2 diabetes c40c41d1
    • Persistence of hyperglycemia after delivery suggests unrecognized pregestational onset of type 1 or type 2 diabetes d2
    • To differentiate between gestational and type 1 or type 2 diabetes, perform standard laboratory testing for diabetes at 6 to 12 weeks after delivery. Test with 1 of 3 methods, using nonpregnant criteriar6 (result must be confirmed by repeated testing; if 1 of the results is abnormal, diabetes likely predated pregnancy)
      • Fasting serum glucose level (126 mg/dL or higher is diagnostic of diabetes) r6
      • Hemoglobin A1C level (6.5% or higher is diagnostic of diabetes) r6
      • 2-hour 75-g oral glucose tolerance test (2-hour glucose level of 200 mg/dL or higher is diagnostic of diabetes) r6
  • Nondiabetic hyperglycemia that develops either pregestationally or during pregnancy c42c43c44
    • May occur as an associated condition in the setting of other rare disorders, such as Cushing syndrome, acromegaly, or pheochromocytoma

Treatment

Goals

  • Primary goals of the metabolic aspect of treatmentr26r1 are to restore fasting and postprandial glucose levels to within reference ranges
  • Target glucose levels r5r11
    • Fasting: 95 mg/dL or less
    • 1-hour postprandial: 140 mg/dL or less
    • 2-hour postprandial: 120 mg/dL or less
  • Hemoglobin A1C levels
    • Target of less than 6% is optimal during pregnancy if it can be achieved without significant hypoglycemia r6
    • Use as a secondary measure of glycemic control in pregnancy, after blood glucose monitoring r6
      • Hemoglobin A1C levels fall during normal pregnancy owing to increased RBC turnover
      • Hemoglobin A1C levels do not capture postprandial hyperglycemia, which is the major factor underlying macrosomia
  • Goals of obstetric management are the following:
    • Deliver healthy neonates by reducing fetal adiposity, birth weight, and instances of large-for-gestational-age status r1r4r27
    • Avoid maternal complications r4

Disposition

Recommendations for specialist referral

  • Refer all patients to a registered dietitian for individualized medical nutrition therapy
  • Refer all patients to a diabetes educator for education on blood glucose monitoring
  • Refer patients with gestational diabetes that requires pharmacotherapy to an endocrinologist; ideal management is in a multidisciplinary setting with endocrine and maternal-fetal medicine specialists

Treatment Options

Lifestyle modifications (eg, medical nutrition therapy, exercise, weight management) are used as first line therapy r5

  • Lifestyle measures alone may be sufficient for many patients (approximately 70%-85%) r28
  • Medications are added if needed to achieve treatment targets

Metabolic surveillance is an essential component of management r5

  • Most patients with gestational diabetes should monitor fasting and postprandial capillary blood glucose levels as a strategy to achieve optimal metabolic control r5
  • Insulin-treated patients in particular must monitor capillary blood glucose levels while fasting and at 1 or 2 hours after eating to guide adjustment of insulin doses
    • Continuous glucose monitoring can be useful to optimize glycemic control in addition to blood glucose monitoring r5r29

Intensified metabolic therapy, using pharmacotherapy, is required in the following situations: r5

  • Maternal metabolic goals are not met (when more than 25% of glucose monitoring values are above fasting/preprandial or postprandial targets)
  • Obstetric fetal ultrasonography finds signs of excessive fetal growth (ie, abdominal circumference above 75th percentile, macrosomia)

Choice of pharmacotherapy

  • First line pharmacotherapy (when required) is insulin r5r11
    • Insulin can provide tight glycemic control, does not cross placenta, and has an extensive history and safety record r11r27
    • Insulin is always required for patients with type 1 diabetes and is typically required for management of patients who have pregestational type 2 diabetes
  • Oral hypoglycemic agents are used as alternatives (these cross the placenta and are less preferred)
    • Reserved primarily for patients who decline insulin or for whom insulin administration may not be safe r30
    • Lingering concerns persist among many experts regarding lack of long-term safety data and possible adverse developmental programming effects associated with oral hypoglycemic agents r31
      • Exposure in utero may produce an adverse metabolic/obesogenic phenotype in offspring
    • Preferred oral agent is also controversial
      • American Diabetes Association cautiously suggests use of either metformin or glyburide (glibenclamide) as alternatives to insulin r5
      • American College of Obstetricians and Gynecologists, Diabetes Canada, and Society for Maternal-Fetal Medicine suggest use of metformin in preference to glyburide r11r20r32
      • Studies have shown that metformin and glyburide have comparable effects on glycemia and incidence of adverse effects,r34 but more recent evidence suggests that glyburide does not yield equivalent outcomes compared with insulin or metformin r11r33

Delivery

  • Patients with good glycemic control and no complications may deliver at term r11
    • Those with control by diet and exercise may be managed expectantly until 40 6/7 weeks
    • Those with control by pharmacotherapy should have delivery between 39 0/7 and 39 6/7 weeks
  • Timing of delivery in patients with poorly controlled diabetes is controversial r11r22
    • Take into consideration risk of prematurity versus risk of stillbirth
    • Induction of labor between 37 0/7 weeks and 38 6/7 weeks is reasonable, with earlier delivery reserved for patients whose condition is refractory to inpatient treatment and those with abnormal results on antepartum fetal testing
  • Mode of delivery should take into consideration estimated fetal size r11
    • Scheduled cesarean delivery may be considered when estimated fetal weight is 4500 g or more (to minimize risk of birth trauma associated with macrosomia)
  • Manage intrapartum blood glucose levels (to avoid maternal hyperglycemia and neonatal hypoglycemia)
    • Suggested blood glucose target range is 72 to 126 mg/dL r10r20

Postpartum management r20

  • Recommend breastfeeding immediately after delivery (to prevent neonatal hypoglycemia) and encourage mother to continue it for at least 4 months
    • Breastfeeding reduces adverse outcomes (eg, childhood obesity and diabetes, maternal type 2 diabetes and hypertension) r35
  • Recommend weight loss to achieve BMI in reference range (to reduce risk of development of type 2 diabetes or gestational diabetes in a subsequent pregnancy)

Drug therapy

  • Insulin c45
    • Indicated for pregnant patients who meet criteria diagnostic of overt diabetes or for whom metabolic goals have not been met through lifestyle modification
    • Insulin is the preferred medication for treating hyperglycemia in gestational diabetes according to the American Diabetes Association r5
    • Usually administered as multiple daily injections but can be delivered with continuous subcutaneous infusion
      • Delivery methods appear to be equally effective; evidence does not support one over the other, but advances in technology may change this
    • Initiation of insulin r11
      • If insulin is used throughout the day in patients in whom fasting and postprandial hyperglycemia are present after most meals, a typical starting total dosage is 0.7 to 1 units/kg daily; this dosage should be divided with a regimen of multiple injections using long-acting or intermediate-acting insulin in combination with rapid-acting insulin r36
      • If there are only isolated abnormal values at a specific time of day, use insulin to target the specific time range during which hyperglycemia is observed
        • Examples: give a dose of intermediate-acting insulin at nighttime to avoid elevated morning fasting glucose levels; or, give a dose of rapid-acting insulin before breakfast to avoid elevated postprandial glucose levels
    • Insulin adjustments
      • Insulin usually needs to be continuously adjusted to achieve glycemic targets r20
        • Adjust insulin dosing on an individualized basis to keep fasting, preprandial, and 1- or 2-hour postprandial values within target ranges
      • At onset of labor, insulin requirements typically decrease but must be carefully monitored and adjusted
        • Discontinue insulin therapy in those patients with gestational diabetes (not type 1 diabetes) during labor or at delivery. Patients with type 1 diabetes always require exogenous insulin on board
    • Short-acting insulin
      • Regular insulin c46
        • For pregnant patients with gestational-onset diabetes not controlled by diet therapy alone
          • Insulin Regular (Recombinant) Solution for injection; Adults and Adolescents (pregnant females): Dosing must be individualized. For women with persistent fasting and postprandial hyperglycemia after most meals, initial total daily insulin requirements are roughly 0.7 to 1 units/kg/day. This dosage should be divided with a regimen of multiple injections using long-acting or intermediate-acting insulin in combination with short-acting insulin. If only isolated abnormal values are present at a specific time of day, focus the insulin regimen to correct the specific hyperglycemia. During labor, requirements change. Insulin is often discontinued during or after labor.
        • For pregnant patients with preexisting diabetes (before pregnancy)
          • Insulin Regular (Recombinant) Solution for injection; Adults and Adolescents (pregnant females): On average, insulin needs increase from a range of 0.7 to 0.8 units/kg of actual body weight/day in the first trimester to 0.8 to 1 units/kg/day in the second trimester, to 0.9 to 1.2 units/kg/day in the third trimester; individualize dosage. The daily dose is usually divided and administered in varying ratios of long-acting or intermediate-acting insulin: short-acting insulin, to fit individual patient needs. During labor and postpartum, hyperglycemia must be closely managed due to the changes in insulin requirements and variable calorie intake.
    • Rapid-acting insulin analogs
      • Insulin lispro c47
        • For pregnant patients with gestational-onset diabetes not controlled by diet therapy alone
          • Insulin Lispro Solution for injection; Adults and Adolescents (pregnant females): Dosing must be individualized. For women with persistent fasting and postprandial hyperglycemia after most meals, initial total daily insulin requirements are roughly 0.7 to 1 units/kg/day. This dosage should be divided with a regimen of multiple injections using long-acting or intermediate-acting insulin in combination with short-acting insulin. If only isolated abnormal values are present at a specific time of day, focus the insulin regimen to correct the specific hyperglycemia. During labor, requirements change. Insulin is often discontinued during or after labor.
        • For pregnant patients with preexisting diabetes (before pregnancy)
          • Insulin Lispro Solution for injection; Adults and Adolescents (pregnant females): On average, insulin needs increase from a range of 0.7 to 0.8 units/kg of actual body weight/day in the first trimester, to 0.8 to 1 units/kg/day in the second trimester, to 0.9 to 1.2 units/kg/day in the third trimester; individualize dosage. The daily dose is usually divided and administered in varying ratios of long-acting or intermediate-acting insulin: short-acting insulin, to fit individual patient needs. During labor and postpartum, hyperglycemia must be closely managed due to the changes in insulin requirements and variable calorie intake.
      • Insulin aspart c48
        • For pregnant patients with gestational-onset diabetes not controlled by diet therapy alone
          • Insulin Aspart (Recombinant) Solution for injection; Adults and Adolescents (pregnant females): Dose guidelines vary and must be individualized. For women with persistent fasting and postprandial hyperglycemia after most meals, initial suggested daily insulin requirements are roughly 0.7 to 1 units/kg/day. This dosage should be divided with a regimen of multiple injections using long-acting or intermediate-acting insulin in combination with short-acting insulin. If only isolated abnormal values are present at a specific time of day, the insulin regimen should be focused to correct the specific hyperglycemia. During labor, requirements change. Insulin is often discontinued during or after labor.
        • For pregnant patients with preexisting diabetes (before pregnancy)
          • Insulin Aspart (Recombinant) Solution for injection; Adults and Adolescents (pregnant females): On average, insulin needs increase from a range of 0.7 to 0.8 units/kg of actual body weight/day in the first trimester to 0.8 to 1 units/kg/day in the second trimester, to 0.9 to 1.2 units/kg/day in the third trimester; individualize dosage. The daily dose is usually divided and administered in varying ratios of long-acting or intermediate-acting insulin: short-acting insulin, to fit individual patient needs. During labor and postpartum, hyperglycemia must be closely managed due to the changes in insulin requirements and variable calorie intake.
    • Intermediate-acting insulin c49
      • May be used in combination with regular insulin for longer-acting glycemic control.
      • Insulin Suspension Isophane (NPH) (Recombinant) Suspension for injection; Adults and Adolescents (pregnant females): Dosing must be individualized. For women with persistent fasting and postprandial hyperglycemia after most meals, initial total daily insulin requirements are roughly 0.7 to 1 units/kg/day. This dosage should be divided with a regimen of multiple injections using long-acting or intermediate-acting insulin in combination with short-acting insulin. If only isolated abnormal values are present at a specific time of day, focus the insulin regimen to correct the specific hyperglycemia. During labor, requirements change. Insulin is often discontinued during or after labor.
    • Long-acting insulin analogs
      • For pregnant patients with preexisting diabetes (before pregnancy)
      • Insulin detemir c50
        • Insulin Detemir (Recombinant) Solution for injection; Adults and Adolescents (pregnant females): Dose guidelines vary and must be individualized. Initial suggested daily insulin requirements: 0.3 to 0.7 units/kg/day; requirements usually increase during second and third trimesters (0.8 units/kg/day or more). During labor, requirements decrease; usually return to normoglycemia several days postpartum. Insulin is often discontinued during or after labor.
      • Insulin glargine c51
        • Insulin Glargine for injection; Adults and Adolescents (pregnant females): Dose guidelines vary and must be individualized. Initial suggested daily insulin requirements: 0.3 to 0.7 units/kg/day; requirements usually increase during second and third trimesters (0.8 units/kg/day or more). During labor, requirements decrease; usually return to normoglycemia several days postpartum. Insulin is often discontinued during or after labor.
  • Oral hypoglycemic medications c52
    • Indicated for pregnant patients whose metabolic goals are not met with lifestyle approaches alone, for those who decline insulin, and for those in whom insulin administration may not be safe
    • Glyburide c53
      • Glyburide’s glycemic control is comparable with that of insulin, but glyburide may cross the placenta and lacks long-term safety data r37
        • Glyburide Oral tablet; Adults (pregnant females): 1.25 mg PO twice daily initially, titrated by no more than 5 mg/day PO each week, up to 10 mg PO twice daily, has been studied. Recommended Max: 10 mg PO twice daily. Long-term safety is not established; not a first-line treatment for gestational diabetes mellitus (GDM) or pregnant patients with pre-existing type 2 diabetes mellitus (T2DM) per ACOG and the ADA.
    • Metformin hydrochloride c54
      • Metformin Hydrochloride Oral tablet; Adult females: 500 mg PO once nightly for 1 week, then titrate to 500 mg PO twice daily. May further titrate the daily dose by 500 mg every 1 to 2 weeks to attain glycemic targets. Max: If needed, up to 2.5 to 3 grams/day PO, given in 2 or 3 divided doses has been studied; metformin is not the first-line choice for women with GDM.

Nondrug and supportive care

  • Medical nutrition therapy c55
    • Cornerstone of metabolic management with oversight by a registered dietitian (familiar with the management of gestational diabetes) ongoing throughout pregnancy r38
    • Adjust initial caloric prescription (35-38 kcal/kg of ideal body weight) as needed to maintain weight gain within the range appropriate for the prepregnancy weight r39
    • Moderate caloric restrictionr40 (25% below level of standard diets) results in some correction of hyperglycemia c56
    • Dietary composition that best optimizes perinatal maternal and fetal outcomes is not known r38
      • Type of diet employed does not appear to affect most maternal outcomes (eg, hypertensive disorders of pregnancy, type 2 diabetes) or neonatal outcomes (eg, large-for-gestational-age status, mortality, morbidity, neurosensory disability) r41
      • Small reduction in rates of cesarean delivery has been observed in patients who consume a DASH diet (Dietary Approaches to Stop Hypertension) r41
      • Other short-term outcomes are similar, comparing strategies such as low-moderate glycemic index diet versus moderate glycemic index diet, DASH diet versus control diet, low-carbohydrate diet versus high-carbohydrate diet, and high-unsaturated-fat diet versus low-unsaturated-fat diet r41
    • Macronutrient requirements
      • Dietary Reference Intake for all pregnant patients, including those with gestational diabetes, specifies a minimum of 175 grams of carbohydrates, a minimum of 71 grams of protein (or 1.1 g/kg/day protein), and 28 grams of fiber r5
      • Available evidence does not identify the ideal amount (grams or percent of total calories) of carbohydrates to achieve glycemic targets
  • Exercise c57
    • May improve glycemic controlr42r43 when performed at moderate intensity at least 3 times per weekr42
    • Moderate exercise is safe and effective in reducing both fasting and postprandial blood glucose levelsr5 in patients with gestational diabetes
      • Moderate exercise is defined as 20-minute intervals of cardiovascular training at a target heart rate approximately 70% of maximum heart rate
      • Examples of moderate intensity physical activity include brisk walking, water aerobics, stationary cycling, resistance training, and household chores r44
    • Patients with gestational diabetes on insulin must take precautions to avoid hypoglycemia r45
  • Effectiveness of lifestyle changes c58
    • Patients participating in lifestyle changes of dietary modifications and physical activity are more likely to achieve postpartum weight goals 1 year after pregnancy r46
    • Patients participating in lifestyle changes of dietary modifications and physical activity have reduced risk of delivering large-for-gestational-age neonates and greater likelihood that neonates will have less adiposity r46
    • A Cochrane review found that lifestyle changes have beneficial effects on maternal health and reduce the risk of infants being large for gestational age r47

Monitoring

  • Antepartum
    • Blood glucose monitoring c59
      • Required for patients treated with insulin during pregnancy
      • Patient monitors glucose levels fasting or postprandially; patients with preexisting diabetes using insulin pumps or basal-bolus therapy must test preprandially as well
        • Preprandial measurements aid in selecting dose of rapid-acting insulin for the next interval
        • Postprandial measurements with hyperglycemic results indicate the need to adjust insulin doses or meal sizes
        • Note that in normal pregnancy, fasting levels of blood glucose are lower than in the nonpregnant state owing to insulin-independent glucose uptake by fetus and placenta
      • Results should be analyzed and acted on ideally by a specialist (eg, endocrinologist, maternal-fetal medicine specialist) in conjunction with registered dietitian
    • Hemoglobin A1C c60
      • Monitor serially at 4- to 8-week intervals until term is reached
    • Fetal surveillance r11c61
      • Fetal assessment beginning at 32 weeks of gestation is recommended in patients with past or present poor glycemic control, which includes all those treated with pharmacotherapy; frequency and type of testing vary
      • Ultrasonography to estimate fetal weight late in third trimester in all patients
  • Postpartum r11
    • Screen for diabetes at 4 to 12 weeks postpartum c62
    • Repeat diabetes screening every 1 to 3 years provided that initial postpartum result has normalized

Complications and Prognosis

Complications

  • Neonatal complications
    • Macrosomia c63
    • Neonatal hypoglycemia c66
    • Hyperbilirubinemia c67d4
    • Childhood obesity c68d5
  • Maternal complications
    • Gestational hypertension c69d6
    • Preeclampsia c70d7
    • Increased risk for cesarean delivery c71
  • Continuous associations exist between detrimental perinatal outcomes and maternal hyperglycemia at levels lower than standard diagnostic thresholds for gestational diabetes or overt diabetes r48
  • Treatment complications
    • Hypoglycemia can develop when mismatches occur between glucose levels and serum concentrations of insulin or oral hypoglycemic agents

Prognosis

  • Patients with gestational diabetes are at increased lifetime risk (relative risk of 7.4) for development of postpartum overt type 2 diabetes compared with patients with normoglycemic pregnancies r49r50
    • Note that patients with previous gestational diabetes should be screened for diabetes every 3 years r6
  • Children born to patients with gestational diabetes have somewhat elevated risk for insulin resistance, metabolic syndrome, cardiovascular disease, and obesity in subsequent decades, although supporting evidence is limited r51r52
  • Treatment of gestational diabetes is associated with improved health outcomes r53

Screening and Prevention

Screening

Screening for hyperglycemia in pregnancy is recommended in asymptomatic pregnant patients r53c72c73c74

  • Screen all patients at 24 to 28 weeks of gestation

At-risk populations

  • Screen patients at high risk of overt diabetes before pregnancy or at first prenatal visit as well as at 24 to 28 weeks
    • This includes patients who are overweight or obese and have 1 or more of the following: r6r11
      • Physical inactivity
      • First-degree relative with diabetes
      • African American, Asian, Native American, Pacific Islander, or Hispanic ethnicity c75c76c77
      • Previous delivery of a macrosomic infant (weighing 4 kg or more)
      • Previous gestational diabetes
      • Hypertension (140/90 mm Hg) or therapy for hypertension
      • Low HDL cholesterol level (35 mg/dL or lower) or high triglyceride level (more than 250 mg/dL)
      • Polycystic ovary syndrome
      • History of cardiovascular disease
      • Other conditions associated with insulin resistance
      • Known impaired glucose metabolism

Screening tests

  • Glucose tolerance test c78c79c80
    • 2-hour, 75-g oral glucose tolerance test is most widely recommended by the International Association of the Diabetes and Pregnancy Study Groups and American Diabetes Association r6r8
    • 1-hour, 50-g oral glucose challenge test is recommended by the American College of Obstetricians and Gynecologists, with a 3-hour test to follow for those with an abnormal initial result r11

Prevention

  • Measures to reduce risk of gestational diabetes include diet modification, physical activity, and participation in structured sessions on lifestyle counseling conducted by specifically trained nurses and dietitians r5r54
    • Specific dietary recommendations include consumption of healthful foods (eg, vegetables, fruit, whole-grain products rich in fiber, low-fat dairy products, vegetable fats high in unsaturated fatty acids, fish, low-fat meats) and lower intake of sugar-rich foods r40
    • Specific physical activity recommendations include a minimum of 150 minutes of moderate-intensity activity per week r40
    • Combined interventions that begin before 20 weeks of pregnancy in obese patients or patients with history of earlier gestational diabetes can reduce risk of gestational diabetes by 39% r40
  • Patients planning pregnancy should strive to attain and maintain optimal body weight and to exercise regularly r54c81c82
    • Physical activity in pregnancy provides a slight protection against development of gestational diabetes r55r56
Crowther CA et al: Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. N Engl J Med. 352(24):2477-86, 200515951574Horvath K et al: Effects of treatment in women with gestational diabetes mellitus: systematic review and meta-analysis. BMJ. 340:c1395, 201020360215Kitzmiller JL et al: Gestational diabetes after delivery: short-term management and long-term risks. Diabetes Care. 30(suppl 2):S225-35, 200717596477Pillay J et al: Screening for gestational diabetes: updated evidence report and systematic review for the US Preventive Services Task Force. JAMA. 326(6):539-62, 202134374717American Diabetes Association Professional Practice Committee et al: 15. Management of diabetes in pregnancy: standards of medical care in diabetes-2022. Diabetes Care. 45(Supplement_1):S232-43, 202234964864American Diabetes Association Professional Practice Committee et al: 2. Classification and diagnosis of diabetes: standards of medical care in diabetes-2022. Diabetes Care. 45(Supplement_1):S17-38, 202234964875Asemi Z et al: Magnesium supplementation affects metabolic status and pregnancy outcomes in gestational diabetes: a randomized, double-blind, placebo-controlled trial. Am J Clin Nutr. 102(1):222-9, 201526016859International Association of Diabetes and Pregnancy Study Groups Consensus Panel et al: International Association of Diabetes and Pregnancy Study Groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care. 33(3):676-82, 201020190296Diagnostic criteria and classification of hyperglycaemia first detected in pregnancy: a World Health Organization Guideline. Diabetes Res Clin Pract. 103(3):341-63, 201424847517Blumer I et al: Diabetes and pregnancy: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 98(11):4227-49, 201324194617American College of Obstetricians and Gynecologists Committee on Practice Bulletins–Obstetrics: ACOG Practice Bulletin No. 190: gestational diabetes mellitus. Obstet Gynecol. 131(2):e49-64, 201829370047National Institutes of Health consensus development conference statement: diagnosing gestational diabetes mellitus, March 4-6, 2013. Obstet Gynecol. 122(2 Pt 1):358-69, 201323969806Metzger BE et al: Summary and recommendations of the Fifth International Workshop-Conference on Gestational Diabetes Mellitus. Diabetes Care. 30(suppl 2):S251-60, 200717596481Buchanan TA et al: Gestational diabetes mellitus: risks and management during and after pregnancy. Nat Rev Endocrinol. 8(11):639-49, 201222751341Bajaj K et al: The genetics of diabetic pregnancy. Best Pract Res Clin Obstet Gynaecol. 29(1):102-9, 201525438929Zhang C et al: Genetic variants and the risk of gestational diabetes mellitus: a systematic review. Hum Reprod Update. 19(4):376-90, 201323690305Hayes MG et al: Identification of HKDC1 and BACE2 as genes influencing glycemic traits during pregnancy through genome-wide association studies. Diabetes. 62(9):3282-91, 201323903356Dooley SL et al: Gestational diabetes mellitus: influence of race on disease prevalence and perinatal outcome in a U.S. population. Diabetes. 40(suppl 2):25-9, 19911748260Galtier F: Definition, epidemiology, risk factors. Diabetes Metab. 36(6 Pt 2):628-51, 201021163426Diabetes Canada Clinical Practice Guidelines Expert Committee et al: Diabetes and pregnancy [2018 clinical practice guidelines] [published correction appears in Can J Diabetes. 42(3):337, 2018]. Can J Diabetes. 42(suppl 1):S255-82, 201829650105Farrar D et al: Different strategies for diagnosing gestational diabetes to improve maternal and infant health. Cochrane Database Syst Rev. 1:CD007122, 201525604891Berger H et al: Guideline no. 393--diabetes in pregnancy. J Obstet Gynaecol Can. 41(12):1814-25.e1, 201931785800Saccone G et al: Screening for gestational diabetes mellitus: one step versus two step approach. A meta-analysis of randomized trials. J Matern Fetal Neonatal Med. 1-9, 201830173594Kattini R et al: Early gestational diabetes mellitus screening with glycated hemoglobin: a systematic review. J Obstet Gynaecol Can. 42(11):1379-84, 202032268994Schaefer-Graf UM et al: A randomized trial evaluating a predominantly fetal growth-based strategy to guide management of gestational diabetes in Caucasian women. Diabetes Care. 27(2):297-302, 200414747203Landon MB et al: A multicenter, randomized trial of treatment for mild gestational diabetes. N Engl J Med. 361(14):1339-48, 200919797280Hartling L et al: Benefits and harms of treating gestational diabetes mellitus: a systematic review and meta-analysis for the U.S. Preventive Services Task Force and the National Institutes of Health Office of Medical Applications of Research. Ann Intern Med. 159(2):123-9, 201323712381Johns EC et al: Gestational diabetes mellitus: mechanisms, treatment, and complications. Trends Endocrinol Metab. 29(11):743-54, 201830297319Zaharieva D et al: Continuous glucose monitoring versus self-monitoring of blood glucose to assess glycemia in gestational diabetes. Diabetes Technol Ther. 22(11):822-7, 202032324046Finneran MM et al: Oral agents for the treatment of gestational diabetes. Curr Diab Rep. 18(11):119, 201830267230Barbour LA et al: A cautionary response to SMFM statement: pharmacological treatment of gestational diabetes. Am J Obstet Gynecol. 219(4):367.e1-367.e7, 201829959933Society of Maternal-Fetal Medicine (SMFM) Publications Committee: SMFM statement: pharmacological treatment of gestational diabetes. Am J Obstet Gynecol. 218(5):B2-4, 201829409848Sénat MV et al: Effect of glyburide vs subcutaneous insulin on perinatal complications among women with gestational diabetes: a randomized clinical trial. JAMA. 319(17):1773-80, 201829715355Nachum Z et al: Glyburide versus metformin and their combination for the treatment of gestational diabetes mellitus: a randomized controlled study. Diabetes Care. 40(3):332-7, 201728077460Ley SH et al: Lactation duration and long-term risk for incident type 2 diabetes in women with a history of gestational diabetes mellitus. Diabetes Care. 43(4):793-8, 202032041900Blum AK: Insulin use in pregnancy: an update. Diabetes Spectr. 29(2):92-7, 201627182178Langer O et al: A comparison of glyburide and insulin in women with gestational diabetes mellitus. N Engl J Med. 343(16):1134-8, 200011036118Duarte-Gardea MO et al: Academy of Nutrition and Dietetics gestational diabetes evidence-based nutrition practice guideline. J Acad Nutr Diet. 118(9):1719-42, 201829859757Rasmussen KM et al: New guidelines for weight gain during pregnancy: what obstetrician/gynecologists should know. Curr Opin Obstet Gynecol. 21(6):521-6, 200919809317Koivusalo SB et al: Gestational diabetes mellitus can be prevented by lifestyle intervention: the Finnish Gestational Diabetes Prevention Study (RADIEL): a randomized controlled trial. Diabetes Care. 39(1):24-30, 201626223239Han S et al: Different types of dietary advice for women with gestational diabetes mellitus. Cochrane Database Syst Rev. 2:CD009275, 201728236296Harrison AL et al: Exercise improves glycaemic control in women diagnosed with gestational diabetes mellitus: a systematic review. J Physiother. 62(4):188-96, 201627637772Bgeginski R et al: Effects of weekly-supervised exercise or physical activity counseling on fasting blood glucose in women diagnosed with gestational diabetes mellitus: a systematic review and meta-analysis of randomized trials. J Diabetes. 9(11):1023-32, 201728032459Mottola MF et al: No. 367-2019 Canadian guideline for physical activity throughout pregnancy. J Obstet Gynaecol Can. 40(11):1528-37, 201830297272Savvaki D et al: Guidelines for exercise during normal pregnancy and gestational diabetes: a review of international recommendations. Hormones (Athens). 17(4):521-9, 201830511333Brown J et al: Lifestyle interventions for the treatment of women with gestational diabetes. Cochrane Database Syst Rev. 5:CD011970, 201728472859Martis R et al: Treatments for women with gestational diabetes mellitus: an overview of Cochrane systematic reviews. Cochrane Database Syst Rev. 8:CD012327, 201830103263HAPO Study Cooperative Research Group et al: Hyperglycemia and adverse pregnancy outcomes. N Engl J Med. 358(19):1991-2002, 200818463375Bellamy L et al: Type 2 diabetes mellitus after gestational diabetes: a systematic review and meta-analysis. Lancet. 373(9677):1773-9, 200919465232Gao F et al: Gestational diabetes and health behaviors among women: National Health and Nutrition Examination Survey, 2007-2014. Prev Chronic Dis. 15:E131, 201830367717Gillman MW et al: Maternal gestational diabetes, birth weight, and adolescent obesity. Pediatrics. 111(3):e221-6, 200312612275Boney CM et al: Metabolic syndrome in childhood: association with birth weight, maternal obesity, and gestational diabetes mellitus. Pediatrics. 115(3):e290-6, 200515741354US Preventive Services Task Force et al: Screening for gestational diabetes: US Preventive Services Task Force recommendation statement. JAMA. 326(6):531-8, 202134374716Shepherd E et al: Combined diet and exercise interventions for preventing gestational diabetes mellitus. Cochrane Database Syst Rev. 11:CD010443, 201729129039Sanabria-Martínez G et al: Effectiveness of physical activity interventions on preventing gestational diabetes mellitus and excessive maternal weight gain: a meta-analysis. BJOG. 122(9):1167-74, 201526036300Russo LM et al: Physical activity interventions in pregnancy and risk of gestational diabetes mellitus: a systematic review and meta-analysis. Obstet Gynecol. 125(3):576-82, 201525730218
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