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Gestational diabetes

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Synopsis
Terminology
Diagnosis
Treatment
Complications and Prognosis
Screening and Prevention

Aug.16.2023

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, insulin or oral hypoglycemic agents to achieve specified glycemic targets
Treatment of gestational diabetes can reduce the rate of adverse pregnancy outcomes,^r1^r2 including macrosomia, fetal adiposity, preeclampsia, and gestational hypertension
Patients with gestational diabetes are at higher lifetime risk for development of postpartum type 2 diabetes^r3
Treatment of gestational diabetes is associated with improved health outcomes ^r4

Urgent Action

Treat patients with severe hyperglycemia (ie, glucose levels indicative of overt diabetes) 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 ^r5^r6
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 Groups^r7^r8 are used internationally and are endorsed by WHO,^r9American Diabetes Association^r6^r10, and Endocrine Society^r11
- Defining criteria of American College of Obstetricians and Gynecologists^r12 and NIH^r13 are used primarily in the United States

Classification

Pregnant patients with gestational diabetes are categorized according to the White classification: ^r12^r14
- Class A1: diabetes diagnosed during pregnancy and controlled by diet
- Class A2: diabetes diagnosed during pregnancy and requiring medication

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 ^r15

Risk factors and/or associations

Age

More common in patients older than 25 years ^c7

Genetics

Polygenic influences contribute to risk ^r16^r17^c8
- Increased risk of gestational diabetes in those with variants in TCF7L2, ABCC8, HKDC1, and BACE2 genes ^r16^r18^c9^c10^c11^c12
Maternal history of gestational diabetes or family history of type 2 diabetes imparts strong risk ^c13^c14

Ethnicity/race

Higher rates of gestational diabetes are found in the following populations: ^r19
- African American ^c15
- Hispanic ^c16
- Native American ^c17
- Asian ^c18

Other risk factors/associations

Overweight or obesity^r20 (BMI greater than 25 kg/m²) ^c19^c20
Personal history of glucose intolerance or prior gestational diabetes ^c21^c22
Family history of gestational or type 2 diabetes ^c23
Polycystic ovary syndrome ^c24
Acanthosis nigricans ^r21^c25
Twin gestation ^c26
Hypertension ^c27
Long-term corticosteroid use ^c28
Previous birth of infant weighing more than 4000 g or with shoulder dystocia ^c29^c30
Unexplained perinatal loss or malformation ^c31^c32

Diagnostic Procedures

Primary diagnostic tools

Perform 2-hour 75-g oral glucose tolerance test in all pregnant patients at 24 to 28 weeks of gestation
- 1-step strategy is recommended by the American Diabetes Association and has superseded the older 2-step approach based on a initial 1-hour 50-g oral glucose challenge test ^r6^r7^r11
- May be associated with better perinatal outcomes compared with 2-step approach ^r22
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) ^r6^r12^r21
  - 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: ^r6^r12
    - 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 ^r5^r7
  - If results are not diagnostic of diabetes, test again at 24 to 28 weeks of gestation ^r7^r23

Laboratory

Fasting plasma glucose or serum glucose test ^r7^c33
- 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
2-hour 75-g oral glucose tolerance test ^r6^c36
- Perform at 24 to 28 weeks on all patients not previously diagnosed with gestational diabetes
- Perform test on morning after patient completes 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

Imaging

Fetal ultrasonography
- For patients in whom pregestational diabetes is suspected, begin fetal ultrasonographic surveillance in first trimester to monitor for congenital abnormalities ^c37
- For patients with gestational diabetes, perform fetal ultrasonography between 28 and 36 weeks of gestation to estimate fetal weight and size ^c38
- 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 ^c39^c40^d1
- 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 criteria (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 ^c41^c42^c43
- 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 treatment are to restore fasting and postprandial glucose levels to within reference ranges
Target glucose levels ^r5^r12^r26
- 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^r26
- Use as a secondary measure of glycemic control in pregnancy, after blood glucose monitoring ^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 ^r1^r4^r27
- 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
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 has been shown to aid in optimization of glycemia in pregnancy complicated by type 1 diabetes; however, there is insufficient data to support its use in patients with gestational diabetes ^r5^r29

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 ^r5^r12
- Insulin can provide tight glycemic control, does not cross placenta, and has an extensive history and safety record ^r12^r27
- 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 only when insulin administration may be unsafe or unfeasible ^r5^r30
- Known to cross the placenta and concerns persist among many experts regarding long-term safety 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, American Association of Clinical Endocrinology, Diabetes Canada, and Society for Maternal-Fetal Medicine suggest use of metformin in preference to glyburide ^r12^r21^r26^r32
  - 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 ^r12^r33
  - Both glyburide and metformin failed to provide adequate glycemic outcomes in approximately a quarter of patients with gestational diabetes according to individual randomized controlled trials ^r5

Delivery

Patients with good glycemic control and no complications may deliver at term ^r12
- 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 ^r12^r23
- 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 ^r12
- 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 ^r11^r21

Postpartum management ^r21

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 ^c44
- 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 ^r12
  - If insulin is used throughout the day in patients in whom fasting and postprandial hyperglycemia are present after most meals, the insulin dose 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 ^r21
    - 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 ^c45
    - For pregnant patients with gestational-onset diabetes not controlled by diet alone
      - Insulin Regular (Recombinant) Solution for injection; Adolescents: 0.7 to 1 units/kg/day subcutaneously is the typical starting total daily insulin dose using a regimen of multiple injections of long- or intermediate-acting insulin plus short-acting insulin in cases where fasting and postprandial hyperglycemia are present. Focus the regimen to correct the specific hyperglycemia if there are only isolated abnormal blood glucose values at a particular time of day. Adjust dose based on blood glucose.
      - Insulin Regular (Recombinant) Solution for injection; Adults: 0.7 to 1 units/kg/day subcutaneously is the typical starting total daily insulin dose using a regimen of multiple injections of long- or intermediate-acting insulin plus short-acting insulin in cases where fasting and postprandial hyperglycemia are present. Focus the regimen to correct the specific hyperglycemia if there are only isolated abnormal blood glucose values at a particular time of day. Adjust dose based on blood glucose.
    - For pregnant patients with preexisting diabetes (before pregnancy)
      - Insulin Regular (Recombinant) Solution for injection; Adolescents: 0.7 to 0.8 units/kg in the first trimester, 0.8 to 1 units/kg/day in the second trimester, and 0.9 to 1.2 units/kg/day in the third trimester is the typical total daily insulin dose using a regimen of multiple injections of long- or intermediate-acting insulin plus short-acting insulin. Adjust dose based on blood glucose and glycemic control goal. Base dose on actual body weight.
      - Insulin Regular (Recombinant) Solution for injection; Adults: 0.7 to 0.8 units/kg in the first trimester, 0.8 to 1 units/kg/day in the second trimester, and 0.9 to 1.2 units/kg/day in the third trimester is the typical total daily insulin dose using a regimen of multiple injections of long- or intermediate-acting insulin plus short-acting insulin. Adjust dose based on blood glucose and glycemic control goal. Base dose on actual body weight.
- Rapid-acting insulin analogs
  - Insulin lispro ^c46
    - For pregnant patients with gestational-onset diabetes not controlled by diet alone
      - Insulin Lispro Solution for injection; Adolescents: 0.7 to 1 units/kg/day subcutaneously is the typical starting total daily insulin dose using a regimen of multiple injections of long- or intermediate-acting insulin plus short-acting insulin in cases where fasting and postprandial hyperglycemia are present. Focus the regimen to correct the specific hyperglycemia if there are only isolated abnormal blood glucose values at a particular time of day. Adjust dose based on blood glucose.
      - Insulin Lispro Solution for injection; Adults: 0.7 to 1 units/kg/day subcutaneously is the typical starting total daily insulin dose using a regimen of multiple injections of long- or intermediate-acting insulin plus short-acting insulin in cases where fasting and postprandial hyperglycemia are present. Focus the regimen to correct the specific hyperglycemia if there are only isolated abnormal blood glucose values at a particular time of day. Adjust dose based on blood glucose.
    - For pregnant patients with preexisting diabetes (before pregnancy)
      - Insulin Lispro Solution for injection; Adolescents: 0.7 to 0.8 units/kg in the first trimester, 0.8 to 1 units/kg/day in the second trimester, and 0.9 to 1.2 units/kg/day in the third trimester is the typical total daily insulin dose using a regimen of multiple injections of long- or intermediate-acting insulin plus short-acting insulin. Adjust dose based on blood glucose and glycemic control goal. Base dose on actual body weight.
      - Insulin Lispro Solution for injection; Adults: 0.7 to 0.8 units/kg in the first trimester, 0.8 to 1 units/kg/day in the second trimester, and 0.9 to 1.2 units/kg/day in the third trimester is the typical total daily insulin dose using a regimen of multiple injections of long- or intermediate-acting insulin plus short-acting insulin. Adjust dose based on blood glucose and glycemic control goal. Base dose on actual body weight.
  - Insulin aspart ^c47
    - For pregnant patients with gestational-onset diabetes not controlled by diet alone
      - Insulin Aspart (Recombinant) Solution for injection; Adolescents: 0.7 to 1 units/kg/day subcutaneously is the typical starting total daily insulin dose using a regimen of multiple injections of long- or intermediate-acting insulin plus short-acting insulin in cases where fasting and postprandial hyperglycemia are present. Focus the regimen to correct the specific hyperglycemia if there are only isolated abnormal blood glucose values at a particular time of day. Adjust dose based on blood glucose.
      - Insulin Aspart (Recombinant) Solution for injection; Adults: 0.7 to 1 units/kg/day subcutaneously is the typical starting total daily insulin dose using a regimen of multiple injections of long- or intermediate-acting insulin plus short-acting insulin in cases where fasting and postprandial hyperglycemia are present. Focus the regimen to correct the specific hyperglycemia if there are only isolated abnormal blood glucose values at a particular time of day. Adjust dose based on blood glucose.
    - For pregnant patients with preexisting diabetes (before pregnancy)
      - Insulin Aspart (Recombinant) Solution for injection; Adolescents: 0.7 to 0.8 units/kg in the first trimester, 0.8 to 1 units/kg/day in the second trimester, and 0.9 to 1.2 units/kg/day in the third trimester is the typical total daily insulin dose using a regimen of multiple injections of long- or intermediate-acting insulin plus short-acting insulin. Adjust dose based on blood glucose and glycemic control goal. Base dose on actual body weight.
      - Insulin Aspart (Recombinant) Solution for injection; Adults: 0.7 to 0.8 units/kg in the first trimester, 0.8 to 1 units/kg/day in the second trimester, and 0.9 to 1.2 units/kg/day in the third trimester is the typical total daily insulin dose using a regimen of multiple injections of long- or intermediate-acting insulin plus short-acting insulin. Adjust dose based on blood glucose and glycemic control goal. Base dose on actual body weight.
- Intermediate-acting insulin ^c48
  - May be used in combination with regular insulin for longer-acting glycemic control.
  - Isophane insulin (neutral protamine Hagedorn)
    - For pregnant patients with gestational-onset diabetes not controlled by diet alone
      - Insulin Suspension Isophane (NPH) (Recombinant) Suspension for injection; Adolescents: 0.7 to 1 units/kg/day subcutaneously is the typical starting total daily insulin dose using a regimen of multiple injections of long- or intermediate-acting insulin plus short-acting insulin in cases where fasting and postprandial hyperglycemia are present. Focus the regimen to correct the specific hyperglycemia if there are only isolated abnormal blood glucose values at a particular time of day. Adjust dose based on blood glucose.
      - Insulin Suspension Isophane (NPH) (Recombinant) Suspension for injection; Adults: 0.7 to 1 units/kg/day subcutaneously is the typical starting total daily insulin dose using a regimen of multiple injections of long- or intermediate-acting insulin plus short-acting insulin in cases where fasting and postprandial hyperglycemia are present. Focus the regimen to correct the specific hyperglycemia if there are only isolated abnormal blood glucose values at a particular time of day. Adjust dose based on blood glucose.
    - For pregnant patients with preexisting diabetes (before pregnancy)
      - Insulin Suspension Isophane (NPH) (Recombinant) Suspension for injection; Adolescents: 0.7 to 0.8 units/kg in the first trimester, 0.8 to 1 units/kg/day in the second trimester, and 0.9 to 1.2 units/kg/day in the third trimester is the typical total daily insulin dose using a regimen of multiple injections of long- or intermediate-acting insulin plus short-acting insulin. Adjust dose based on blood glucose and glycemic control goal. Base dose on actual body weight.
      - Insulin Suspension Isophane (NPH) (Recombinant) Suspension for injection; Adults: 0.7 to 0.8 units/kg in the first trimester, 0.8 to 1 units/kg/day in the second trimester, and 0.9 to 1.2 units/kg/day in the third trimester is the typical total daily insulin dose using a regimen of multiple injections of long- or intermediate-acting insulin plus short-acting insulin. Adjust dose based on blood glucose and glycemic control goal. Base dose on actual body weight.
- Long-acting insulin analogs
  - Insulin detemir ^c49
    - For pregnant patients with gestational-onset diabetes not controlled by diet alone
      - Insulin Detemir (Recombinant) Solution for injection; Adolescents: 0.7 to 1 units/kg/day subcutaneously is the typical starting total daily insulin dose using a regimen of multiple injections of long- or intermediate-acting insulin plus short-acting insulin in cases where fasting and postprandial hyperglycemia are present. Focus the regimen to correct the specific hyperglycemia if there are only isolated abnormal blood glucose values at a particular time of day. Adjust dose based on blood glucose.
      - Insulin Detemir (Recombinant) Solution for injection; Adults: 0.7 to 1 units/kg/day subcutaneously is the typical starting total daily insulin dose using a regimen of multiple injections of long- or intermediate-acting insulin plus short-acting insulin in cases where fasting and postprandial hyperglycemia are present. Focus the regimen to correct the specific hyperglycemia if there are only isolated abnormal blood glucose values at a particular time of day. Adjust dose based on blood glucose.
    - For pregnant patients with preexisting diabetes (before pregnancy)
      - Insulin Detemir (Recombinant) Solution for injection; Adolescents: 0.7 to 0.8 units/kg in the first trimester, 0.8 to 1 units/kg/day in the second trimester, and 0.9 to 1.2 units/kg/day in the third trimester is the typical total daily insulin dose using a regimen of multiple injections of long- or intermediate-acting insulin plus short-acting insulin. Adjust dose based on blood glucose and glycemic control goal. Base dose on actual body weight.
      - Insulin Detemir (Recombinant) Solution for injection; Adults: 0.7 to 0.8 units/kg in the first trimester, 0.8 to 1 units/kg/day in the second trimester, and 0.9 to 1.2 units/kg/day in the third trimester is the typical total daily insulin dose using a regimen of multiple injections of long- or intermediate-acting insulin plus short-acting insulin. Adjust dose based on blood glucose and glycemic control goal. Base dose on actual body weight.
  - Insulin glargine ^c50
    - For pregnant patients with gestational-onset diabetes not controlled by diet alone
      - Insulin Glargine Solution for injection; Adolescents: 0.7 to 1 units/kg/day subcutaneously is the typical starting total daily insulin dose using a regimen of multiple injections of long- or intermediate-acting insulin plus short-acting insulin in cases where fasting and postprandial hyperglycemia are present. Focus the regimen to correct the specific hyperglycemia if there are only isolated abnormal blood glucose values at a particular time of day. Adjust dose based on blood glucose.
      - Insulin Glargine Solution for injection; Adults: 0.7 to 1 units/kg/day subcutaneously is the typical starting total daily insulin dose using a regimen of multiple injections of long- or intermediate-acting insulin plus short-acting insulin in cases where fasting and postprandial hyperglycemia are present. Focus the regimen to correct the specific hyperglycemia if there are only isolated abnormal blood glucose values at a particular time of day. Adjust dose based on blood glucose.
    - For pregnant patients with preexisting diabetes (before pregnancy)
      - Insulin Glargine Solution for injection; Adolescents: 0.7 to 0.8 units/kg in the first trimester, 0.8 to 1 units/kg/day in the second trimester, and 0.9 to 1.2 units/kg/day in the third trimester is the typical total daily insulin dose using a regimen of multiple injections of long- or intermediate-acting insulin plus short-acting insulin. Adjust dose based on blood glucose and glycemic control goal. Base dose on actual body weight.
      - Insulin Glargine Solution for injection; Adults: 0.7 to 0.8 units/kg in the first trimester, 0.8 to 1 units/kg/day in the second trimester, and 0.9 to 1.2 units/kg/day in the third trimester is the typical total daily insulin dose using a regimen of multiple injections of long- or intermediate-acting insulin plus short-acting insulin. Adjust dose based on blood glucose and glycemic control goal. Base dose on actual body weight.
Oral hypoglycemic medications ^c51
- Indicated for pregnant patients whose metabolic goals are not met with lifestyle approaches alone and who decline insulin or those in whom insulin administration may not be safe
- Glyburide ^c52
  - Glyburide Oral tablet; Adults: 2.5 mg PO once daily, initially. Increase the dose by 2.5 to 5 mg/day weekly as needed. Usual Max: 20 mg/day. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
- Metformin ^c53
  - Metformin Hydrochloride Oral tablet; Adults: 500 mg PO once nightly for 1 week, then 500 mg PO twice daily. May increase the dose further if needed up to 2.5 to 3 g/day divided in 2 or 3 doses.

Nondrug and supportive care

Medical nutrition therapy ^c54
- Cornerstone of metabolic management with oversight by a registered dietitian (familiar with the management of gestational diabetes) ongoing throughout pregnancy ^r37
- 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 ^r38
- Moderate caloric restriction^r39 (25% below level of standard diets) results in some correction of hyperglycemia ^c55
- Dietary composition that best optimizes perinatal maternal and fetal outcomes is not known ^r37
  - 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) ^r40^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
  - Academy of Nutrition and Dietetics guidelines recommend pregnant patients with a healthy BMI follow a customized meal plan that distributes total daily carbohydrate intake over three main meals and two or more snacks, with each meal separated by at least two, but no more than 12 hours ^r37^r40
- Overweight and obese patients should follow a calorie-restricted diet that includes sufficient calories and carbohydrates to avoid maternal ketosis ^r40
- 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 ^c56
- May improve glycemic control^r42^r43 when performed at moderate intensity at least 3 times per week^r42
- Moderate exercise is safe and effective in reducing both fasting and postprandial blood glucose levels in patients with gestational diabetes ^r5
  - 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 ^c57
- 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 ^c58
  - 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
  - Continuous glucose monitoring when used in addition to traditional pre- and postprandial blood glucose monitoring, can help achieve hemoglobin A1C goals and reduce macrosomia and neonatal hypoglycemia in pregnancy complicated by type 1 diabetes; however, there is insufficient data to support its use in patients with gestational diabetes ^r5
- Hemoglobin A1C ^c59
  - Monitor serially at 4- to 8-week intervals until term is reached
- Fetal surveillance ^r12^c60
  - 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 ^r12
- Screen for diabetes at 4 to 12 weeks postpartum with a fasting 2-hour 75-g oral glucose tolerance test using nonpregnancy criteria ^r5^c61
- Repeat diabetes screening every 1 to 3 years provided that initial postpartum result has normalized

Complications and Prognosis

Complications

Continuous associations exist between detrimental perinatal outcomes and maternal hyperglycemia at levels lower than standard diagnostic thresholds for gestational diabetes or overt diabetes ^r48
Neonatal complications ^r49^r50^r51
- Large for gestational age and macrosomia ^c62
  - Shoulder dystocia ^c63^d3
  - Birth trauma ^c64
  - Operative delivery
- Respiratory distress
- Neonatal jaundice ^c65^d4
- Neonatal hypoglycemia ^c66
- Childhood obesity ^c67^d5
- Preterm birth
- Stillbirth ^r51
Maternal complications
- Hypertension ^c68^d6
- Preeclampsia ^c69^d7
- Polyhydramnios
- Increased risk for cesarean delivery ^c70
- Hypoglycemia secondary to treatment
Tighter blood glucose targets (fasting blood glucose 90 mg/dL or less, 1-hour postprandial 133 mg/dL or less, 2-hour postprandial 121 mg/dL or less) did not reduce the risk of having a large for gestational age neonate compared to less tight targets (fasting blood glucose 99 mg/dL or less, 1-hour postprandial 144 mg/dL or less, 2-hour postprandial 126 mg/dL or less) but did reduce the risk of perinatal death, birth trauma, or shoulder dystocia in a randomized trial ^r52
- Tighter control was associated with an increase in serious maternal morbidity (the composite of major hemorrhage, coagulopathy, embolism, and obstetric complications)

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 ^r53^r54
- Note that patients with previous gestational diabetes should be screened for diabetes at least 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 ^r55^r56
Treatment of gestational diabetes is associated with improved health outcomes ^r57

Screening and Prevention

Screening

Screening for hyperglycemia in pregnancy is recommended in asymptomatic pregnant patients ^r57^c71^c72^c73

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: ^r6^r12
  - Physical inactivity
  - First-degree relative with diabetes
  - African American, Asian, Native American, Pacific Islander, or Hispanic ethnicity ^c74^c75^c76
  - Previous delivery of a macrosomic infant (weighing 4000 g 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 ^c77^c78^c79
- 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 ^r6^r7
- Previously a 1-hour, 50-g oral glucose challenge test was recommended by the American College of Obstetricians and Gynecologists, with a 3-hour test to follow for those with an abnormal initial result ^r12

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 ^r5^r58
- 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 ^r39
- Specific physical activity recommendations include a minimum of 150 minutes of moderate-intensity activity per week ^r39
- 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% ^r39
Patients planning pregnancy should strive to attain and maintain optimal body weight and to exercise regularly ^r58^c80^c81
- Physical activity in pregnancy provides a slight protection against development of gestational diabetes ^r59^r60

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