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Sep.16.2021

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
  • Women with gestational diabetes are at higher lifetime risk for development of postpartum type 2 diabetesr3

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%r4 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 women meeting criteria for diagnosis when tested between 24 and 28 weeks of pregnancy r4r5
  • Women 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) r5
  • 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 Groupsr6r7 are used internationally and are endorsed by WHO,r8American Diabetes Associationr5, and Endocrine Societyr9
    • Defining criteria of American College of Obstetricians and Gynecologistsr10 and NIHr11 are used primarily in the United States

Classification

  • Pregnant women with either gestational or preexisting diabetes are categorized according to the White classification: r12r13
    • 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 women 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 women at 24 to 28 weeks of gestation
    • Consensus has not been reached regarding optimal strategy; either of the following approaches is acceptable: r5r21
      • Older and most widely used strategy in North America consists of 2 steps r10r20r22
        • 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 r5r7r9
        • 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) r5r10r20
      • Consider in pregnant women 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: r5r10
        • First-degree relative with diabetes
        • High-risk race or ethnicity (eg, African American, Latino, 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 r5r7
      • If results are not diagnostic of diabetes, test again at 24 to 28 weeks of gestation r7r22

Laboratory

  • Fasting plasma glucose or serum glucose test r7c33
    • Diagnostic of gestational diabetes: 92 to 125 mg/dL
    • Diagnostic of overt diabetes: 126 mg/dL or higher (same reference limit as general population) r5
  • 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) r5
  • 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 women than in nonpregnant women (reference ranges differ) r5
    • Diagnostic of overt diabetes: 6.5% or higher r5
    • 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) r5
      • 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 r5
        • 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) r5r10
        • 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 1 of the following diagnostic criteria:
            • Carpenter and Coustan criteria (recommended by American Diabetes Association and American College of Obstetricians and Gynecologists) r5r10
              • 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) r10r25
              • 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 r5r10

Imaging

  • Fetal ultrasonography
    • For women in whom pregestational diabetes is suspected, begin fetal ultrasonographic surveillance in first trimester to monitor for congenital abnormalities c38
    • For women 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,r26 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 criteriar5 (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) r5
      • Hemoglobin A1C level (6.5% or higher is diagnostic of diabetes) r5
      • 2-hour 75 g oral glucose tolerance test (2-hour glucose level of 200 mg/dL or higher is diagnostic of diabetes) r5
  • 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 treatmentr1r27 are to restore fasting and postprandial glucose levels to within reference ranges
  • Target glucose levels r4r10
    • 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 r5
    • Use as a secondary measure of glycemic control in pregnancy, after self-monitoring of blood glucose r5
      • 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 r1r28
    • Avoid maternal complications

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 self-monitoring of blood glucose
  • 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 r4

  • Lifestyle measures alone may be sufficient in many women (approximately 70%-85%) r29
  • Medications are added if needed to achieve treatment targets

Metabolic surveillance is an essential component of management r4

  • Most women with gestational diabetes should monitor fasting and postprandial capillary blood glucose levels as a strategy to achieve optimal metabolic control r4
  • Insulin-treated patients in particular must self-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 self-monitoring r4r30

Intensified metabolic therapy, using pharmacotherapy, is required in the following situations: r4

  • 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 r4r10
    • Insulin can provide tight glycemic control, does not cross placenta, and has an extensive history and safety record r10r28
    • Insulin is always required for patients with type 1 diabetes and is typically required for management of women who have pregestational type 2 diabetes
  • Oral hypoglycemic agents are used as alternatives (cross the placenta and are less preferred)
    • Reserved primarily for women who decline insulin or for whom insulin administration may not be safe r31
    • Lingering concerns persist among many experts regarding lack of long-term safety data and possible adverse developmental programming effects associated with oral hypoglycemic agents r32
      • 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 r4
      • American College of Obstetricians and Gynecologists, Diabetes Canada, and Society for Maternal-Fetal Medicine suggest use of metformin in preference to glyburide r10r20r33
      • Studies have shown that metformin and glyburide have comparable effects on glycemia and incidence of adverse effects,r35 but more recent evidence suggests that glyburide does not yield equivalent outcomes compared with insulin or metformin r10r34

Delivery

  • Women with good glycemic control and no complications may deliver at term r10
    • 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 women with poorly controlled diabetes is controversial r10r22
    • 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 women 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 r10
    • 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 r9r20

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) r36
  • 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 women 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 r4
    • 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 r10
      • If insulin is used throughout the day in women 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 r37
      • 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 women 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 r38
        • 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 r39
    • 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 r40
    • Moderate caloric restrictionr41 (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 r39
      • 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) r42
      • Small reduction in rates of cesarean delivery has been observed in women who consume a DASH diet (Dietary Approaches to Stop Hypertension) r42
      • 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 r42
    • Macronutrient requirements
      • Dietary Reference Intake for all pregnant women, 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 r4
      • 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 controlr43r44 when performed at moderate intensity at least 3 times per weekr44
    • Moderate exercise is safe and effective in reducing both fasting and postprandial blood glucose levelsr45 in women 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 r46
    • Women with gestational diabetes on insulin must take precautions to avoid hypoglycemia r47
  • Effectiveness of lifestyle changes c58
    • Women participating in lifestyle changes of dietary modifications and physical activity are more likely to achieve postpartum weight goals 1 year after pregnancy r48
    • Women 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 r48
    • A Cochrane review found that lifestyle changes have beneficial effects on maternal health and reduce the risk of infants being large for gestational age r49

Monitoring

  • Antepartum
    • Self-monitoring of blood glucose level c59
      • Required for women treated with insulin during pregnancy
      • Patient self-measures glucose levels fasting or postprandially; women 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 r10c61
      • Fetal assessment beginning at 32 weeks of gestation is recommended in women 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 women
  • Postpartum r10
    • 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 r50
  • Treatment complications
    • Hypoglycemia can develop when mismatches occur between glucose levels and serum concentrations of insulin or oral hypoglycemic agents

Prognosis

  • Women with gestational diabetes are at increased lifetime risk (relative risk of 7.4) for development of postpartum overt type 2 diabetes compared with women with normoglycemic pregnancies r51r52
    • Note that women with previous gestational diabetes should be screened for diabetes every 3 years r5
  • Children born to women with gestational diabetes have somewhat elevated risk for insulin resistance, metabolic syndrome, cardiovascular disease, and obesity in subsequent decades, although supporting evidence is limited r53r54

Screening and Prevention

Screening

Screening for hyperglycemia in pregnancy is recommended in asymptomatic pregnant women r55c72c73c74

  • All women should be screened at 24 to 28 weeks of gestation

At-risk populations

  • Women at high risk of overt diabetes should be screened before pregnancy or at first prenatal visit as well as at 24 to 28 weeks
    • This includes women who are overweight or obese and have 1 or more of the following: r5r10
      • 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 r5r7
    • 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 r10

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 r56
    • 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 r57
    • Specific physical activity recommendations include a minimum of 150 minutes of moderate-intensity activity per week r57
    • Combined interventions that begin before 20 weeks of pregnancy in obese women or women with history of earlier gestational diabetes can reduce risk of gestational diabetes by 39% r57
  • Patients planning pregnancy should strive to attain and maintain optimal body weight and to exercise regularly r56c81c82
    • Physical activity in pregnancy provides a slight protection against development of gestational diabetes r58r59
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