Diabetes in Pregnancy

Management

Diabetes in Pregnancy: Management Goals

• Provide preconception care for women with preexisting T1DM or T2DM or a history of GDM– Educate patients to maintain adequate nutrition and glucose

control before conception, during pregnancy, and postpartum1

• Close to normal glycemic control prior to and throughout pregnancy offers substantial benefit for both mother and child2

– Maintenance of normoglycemia prior to and through the first trimester results in a complication risk close to that of women without diabetes3

• For all glucose management protocols, AACE recommendations stress patient safety as the first priority1,4

1. AACE. Endocr Pract. 2011;17(2):1-53. 2. Mathiesen ER, et al. Endocrinol Metab Clin N Am. 2011;40:727-738.3. Castorino K, Jovanovic L. Clin Chem. 2011;57(2):221-30. 4. ADA. Diabetes Care. 2013;36(suppl 1):S11-S66.

Glycemic Targets During Pregnancy: AACE & ADA Guidelines1,2

Glucose Increment

Patients with GDM Patients with

Preexisting T1DM or T2DM

Preprandial, premeal

≤95 mg/dL (5.3 mmol/L) Premeal, bedtime, and overnight glucose:60-99 mg/dL (3.4-5.5 mmol/L)

Postprandial, post-meal

1-hour post-meal: ≤140 mg/dL (7.8 mmol/L) or 2-hour post-meal: ≤120 mg/dL (6.7 mmol/L)

Peak postprandial glucose 100-129 mg/dL(5.5-7.1 mmol/L)

A1C A1C ≤6.0%   

1. AACE. Endocr Pract. 2011;17(2):1-53. 2. ADA. Diabetes Care. 2013;36(suppl 1):S11-66.

Glycemic Targets During Pregnancy: Expert Recommendations

Glucose Increment

Patients With Gestational Diabetes Mellitus (GDM)1

Patients With Preexisting T1DM or

T2DM1,2

Preprandial, premeal

≤90 mg/dL (5.0 mmol/L)1,2

Postprandial, post-meal

1-hour post-meal: ≤120 mg/dL (6.7 mmol/L)1,2

A1C A1C <5.0%3   A1C <6.0%4

1. LeRoith D, et. al. Endocrinol Metab Clin N Am. 2011;40(1): xii-919. 2. Castorino K et al. Curr Diab Rep, 2012;12:53-59.

3. L. Jovanovic; personal communication.4. AACE. Endocr Pract. 2011;17(2):1-53.

Some experts recommend more stringent goals (in particular, for patients on insulin therapy) to prevent maternal and fetal complications1,2

Why Is Glucose Control Essential During Pregnancy?

• For both mothers with diabetes and their infants, risk for adverse health outcomes correlates with maternal glucose levels during the first trimester of pregnancy1

• A large, randomized controlled trial of intensive diabetes management versus standard care in patients with gestational diabetes mellitus (GDM) showed:– Rate of serious perinatal complications was reduced

from 4% to 1% with treatment of GDM2

– Improvements in maternal health-related quality of life2

1. ADA. Diabetes Care. 2013;36(suppl 1):S11-S66. 2. Crowther CA, et al. N Engl J Med. 2005;352(24):2477-86. Epub 2005 Jun 12.

Diabetes in Pregnancy: Avoiding Complications

• Advances in diagnosis and treatment have dramatically reduced morbidity and mortality in both mothers and infants1,2

Preconception care

• Renal impairment, cardiac disease, neuropathy3

Careful evaluationsat each visit

• 1st trimester through 1st year postpartum• Examine active lesions more frequently1

Regular ophthalmologic exams

• Target: systolic BP 110-129 mmHg; diastolic BP 65-79 mmHg

• Lifestyle changes, behavior therapy, and pregnancy-safe medications (ACE inhibitors and ARBs contraindicated in pregnancy)3

Hypertension management

1. AACE. Endocr Pract. 2011;17(2):1-53. 2. Jovanovic L, et al. Diabetes Care. 2011;34(1):53-54.3. Jovanovic L, et al. Mt Sinai J Med. 2009;76(3):269-80. 4. ADA. Diabetes Care. 2013;36(suppl 1):S11-S66.

• Early referral to a specialist is essential1

• Collaborative effort among obstetrician/ midwife, endocrinologist, ophthalmologist, registered dietitian, and nurse educator– All team members should

be engaged in patient education/care prior to and throughout pregnancy2

• Individualized treatment plans, involving a combination of:– Glucose monitoring– Medical nutrition therapy

(MNT)– Pharmacotherapy– Exercise– Weight management

strategies– Psychological support

Diabetes in Pregnancy: Management Approaches

1. Castorino K, Jovanovic L. Clin Chem. 2011;57(2):221-30. 2. Mathiesen ER, et al. Endocrinol Metab Clin N Am. 2011;40:727-738.

Glucose Monitoring in GDM:Self-Monitoring of Blood Glucose• Self-monitoring of blood glucose (SMBG) is the cornerstone of

diabetes management in gestational diabetes mellitus (GDM)1

• ADA guidelines for pregnant patients requiring insulin:– SMBG ≥3 times daily– More frequent SMBG may be required, including:2

• Morning fasting • Premeal (breakfast, lunch, and dinner)• 1-hour postprandial (breakfast, lunch, and dinner)• Before bed3

• Disadvantages include:– Potential for human error or inconsistencies in performing SMBG

and/or self-reporting – Partial glucose profile from intermittent readings; hyper- or

hypoglycemic episodes may go undetected4

1. Jovanovic L, et al. Diabetes Care. 2011;34(1):53-54. 2. ADA. Diabetes Care. 2013;36(suppl 1):S11-S66. 3. Castorino K, Jovanovic L. Clin Chem. 2011;57(2):221-30. 4. Chitayat, L, et al. Diabetes Technol Ther. 2009;11:S105-111.

Glucose Monitoring in GDM: A1C

• Provides valuable supplementary information for glycemic control

• To safely achieve target glucose levels, combine A1C with

frequent self-monitoring of blood glucose (SMBG)1,2

• Recent research suggests weekly A1Cs during pregnancy:1

– SMBG alone can miss certain high glucose values – SMBG + A1C = more complete data for glucose control – Clinicians can further optimize treatment decisions with weekly A1C

• Other important glucose measurements:– Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study

suggests A1C is less useful than OGTT as a predictor of adverse pregnancy outcomes in women with diabetes3

1. Jovanovic L, et al. Diabetes Care. 2011;34(1):53-54. 2. Castorino K, Jovanovic L. Clin Chem. 2011;57(2):221-30.3. Lowe LP, et al. Diabetes Care. 2012;35:574-580.

Glucose Monitoring in GDM: Continuous Glucose Monitoring

• Measures glucose levels over 24-hour period1

– Continuous glucose monitoring (CGM) measures glucose concentration of interstitial fluid using subcutaneous sensor tip implanted in abdominal wall1,3

• Identifies glycemic excursions that may go undetected with SMBG1

– May be recommended when patient unable to achieve target glucose levels with SMBG alone2

• Educational tool to improve treatment adherence4

• Benefits:– Improved glycemic control during third trimester– Reduced infant birth weight– Decreased risk of infant macrosomia1,2,3

1. Hod M. Jovanovic L. Int J Clin Pract, 2010;64(166):47-52. 2. Castorino K, Jovanovic L. Clin Chem. 2011;57(2):221-30.3. Chitayat, L, et al. Diabetes Technology & Therapeutics. 2009;11:S105-111. 4. AACE. Endocr Pract. 2010;16(5):1-16.

CGM Devices:Professional vs Personal

• Professional CGM devices– Owned by a health care professional1

– Typically implanted for 3-5 days1

– Data downloaded and analyzed by a health care professional1

• Personal CGM devices– Owned by the patient – May be implanted for longer periods (eg, several

weeks)1

– Provide continuous feedback on glucose values, which may be read/interpreted by the patient in real time2

1. AACE. Endocr Pract. 2010;16(5):1-16.2. Chitayat, L, et al. Diabetes Technology & Therapeutics. 2009;11:S105-111.

• Refer patients for nutritional counseling with registered dietitian familiar with pregnancy1,2

• MNT is based on standard nutritional recommendations during pregnancy, with customization based on:

– Height

– Weight

– Nutritional assessment

– Level of glycemic control3,4,5

• Goals: – Provide a nutritionally adequate

diet for pregnancy– Achieve normoglycemia

Medical Nutrition Therapy (MNT)

1. Castorino K, Jovanovic L. Clin Chem. 2011;57(2):221-30. 2. Kitzmiller JL, et al. Diabetes Care. 2008;31(5):1060-79. 3. Jovanovic L, et al. Mt Sinai J Med. 2009;76(3):269-80. 4. ADA. Diabetes Care. 2004;27(suppl 1):S88-90.

5. National Academy of Sciences, Institute of Medicine, Food and Nutrition Board, Committee on Nutritional Status in Pregnancy and Lactation, Nutrition During Pregnancy:

http://www.iom.edu/Reports/1990/Nutrition-During-Pregnancy-Part-I-Weight-Gain-Part-II-Nutrient-Supplements.aspx, 1990. Accessed: April 26, 2012.

Target Glucose Levels for Normoglycemia3

Preprandial glucose ≤95 mg/dL (5.3 mmol/L)

1-hour postprandial glucose ≤140 mg/dL (7.8 mmol/L) or

2-hour postprandial glucose ≤120 mg/dL (6.7 mmol/L)

Management of GDM

• Medical nutrition therapy (MNT) and lifestyle changes can effectively manage 80% to 90% of mild GDM cases1,2

• MNT nutritional goals and recommendations:– Choose healthy low-carbohydrate, high-fiber sources of nutrition,

with fresh vegetables as the preferred carbohydrate sources4

– Count carbohydrates and adjust intake based on fasting, premeal, and postprandial SMBG measurements4,6

– Avoid sugars, simple carbohydrates, highly processed foods, dairy, juices, and most fruits4,5

– Eat frequent small meals to reduce risk of postprandial hyperglycemia and preprandial starvation ketosis5

• As pregnancy progresses, glucose intolerance typically worsens; patients may ultimately require insulin therapy1,3

1. Chitayat, L, et al. Diabetes Technology & Therapeutics. 2009;11:S105-111. 2. ADA. Diabetes Care. 2013;36(suppl 1):S11-66.3. ADA. Diabetes Care. 2004;27(suppl 1):S88-90. 4. Castorino K, Jovanovic L. Clin Chem. 2011;57(2):221-30.

5. Jovanovic L, et al. Mt Sinai J Med. 2009;76(3):269-80. 6. Mathiesen ER, et al. Endocrinol Metab Clin N Am. 2011;40:727-738.

Diabetes in Pregnancy: Pharmacologic Therapy

• When MNT alone fails, pharmacologic therapy is indicated– AACE guidelines recommend insulin as the optimal approach1

– Insulin therapy is required for the treatment of T1DM during pregnancy2

• Metformin and the sulfonylurea glyburide are the 2 most commonly prescribed oral antihyperglycemic agents during pregnancy1,2

• Due to efficacy and safety concerns, the ADA does not recommend oral antihyperglycemic agents for gestational diabetes mellitus (GDM) or preexisting T2DM3,4

1. AACE. Endocr Pract. 2011;17(2):1-53. 2. Castorino K, Jovanovic L. Clin Chem. 2011;57(2):221-30.3. ADA. Diabetes Care. 2004;27(suppl 1):S88-90. 4. Jovanovic L, et al. Mt Sinai J Med. 2009;76(3):269-80.

5. Micronase PI. Pifizer. Division of Pifizer, NY, NY, 2010. 6. Diabeta PI. Sanofi-Aventis U.S. Bridgewater, NJ, 2009.

Medication Crosses Placenta

Classification Notes

Metformin Yes Category B1 Metformin and glyburide may be insufficient to maintain normoglycemia at all times, particularly during postprandial periods2

Glyburide Minimal transfer

Some formulations category B, others category C1,5,6

Insulin Use During Pregnancy

Patient Education• Insulin administration, dietary modifications in response to self-monitoring of blood glucose

(SMBG), hypoglycemia awareness and management1

Basal Insulin• Intermediate- or long-acting insulin administered by injection, or• Rapid-acting insulin administered by insulin pump2,3

Postprandial Hyperglycemia

• Recommended approach: rapid-acting insulin analogues2

• Alternative approach: regular insulin to control postprandial glucose spikes; must be administered 60-90 minutes prior to meals (considered less effective than rapid-acting insulin and may increase hypoglycemia risk)3

Insulin Options• Insulin NPH: safe intermediate alternative (category B)2

• Insulin detemir: safe long-acting alternative (category B)2,3

• Lispro and aspart: safe rapid-acting insulin analogues (category B)2,3

• Insulin glargine: frequently prescribed in pregnancy; however, safety in pregnancy has not been definitively established (category C)2,3

1. Jovanovic L, et al. Mt Sinai J Med. 2009;76(3):269-80. 2. AACE. Endocr Pract. 2011;17(2):1-53.3. Castorino K, Jovanovic L. Clin Chem. 2011;57(2):221-30. 4. ADA. Diabetes Care. 2004;27(suppl 1):S88-90.

Glucose Levels for Insulin Initiation in GDM1

Fasting plasma glucose ≤105 mg/dL (5.8 mmol/L)

1-hour postprandial plasma glucose ≤155 mg/dL (8.6 mmol/L)

2-hour postprandial plasma glucose ≤130 mg/dL (7.2 mmol/L)

Gestational Diabetes Mellitus (GDM): Initiation of Insulin

1. ADA. Diabetes Care. 2004;27(suppl 1):S88-90.

Diabetes in Pregnancy: InsulinInsulin Options Shown to Be Safe During Pregnancy1

Name Type OnsetPeak Effect

DurationRecommended Dosing Interval

AspartRapid-acting

(bolus) 15 min 60 min 2 hrs

Start of each meal

Lispro Rapid-acting

(bolus) 15 min 60 min 2 hrs

Start of each meal

Regular insulin

Intermediate-acting

60 min 2-4 hrs 6 hrs60-90 minutes before meal

NPH Intermediate-acting (basal)

2 hrs 4-6 hrs 8 hrs Every 8 hours

Detemir Long-acting

(basal) 2 hrs n/a 12 hrs Every 12 hours

1. Castorino K, Jovanovic L. Clin Chem. 2011;57(2):221-30.2. Kitzmiller JL, et al. Diabetes Care. 2008;31(5):1060-79.

Following a positive pregnancy test, patients with preexisting diabetes being treated with insulin or oral antihyperglycemic medications should be transitioned to one of the above options2

Diabetes in Pregnancy: Insulin Dosing

Insulin Dosing Guidelines During Pregnancy and Postpartum1

Weeks gestation Total daily dose (TDD) of insulin†

1-13 weeks (0.7 x weight in kg) or (0.30 x weight [lbs])

14-26 weeks (0.8 x weight in kg) or (0.35 x weight [lbs])

27-37 weeks (0.9 x weight in kg) or (0.40 x weight [lbs])

38 weeks to delivery (1.0 x weight in kg) or (0.45 x weight [lbs])

Postpartum (and lactation)‡ (0.55 x weight in kg) or (0.25 x weight [lbs])† The total daily dose (TDD) of insulin should be split, so that 50% is used for basal insulin and 50% is used for premeal rapid-acting insulin boluses‡ Nighttime basal insulin should be decreased by 50% in lactating women (to prevent severe hypoglycemia)• Special notes for T1DM:

• Between 10 and 14 weeks gestation, patients with T1DM undergo a period of increased insulin sensitivity; insulin dosage may need to be reduced accordingly during this time frame

• From weeks 14 through 35 of gestation, insulin requirements typically increase steadily • After 35 weeks gestation, insulin requirements may level off or even decline2

• Obese patients may require higher insulin dosages than non-obese individuals2

1. Castorino K, Jovanovic L. Clin Chem. 2011;57(2):221-30. 2. Kitzmiller JL, et al. Diabetes Care. 2008;31(5):1060-79.

Insulin Pump Therapy/Continuous Subcutaneous Insulin Infusion (CSII)

• CSII: Administration of rapid-acting insulin via insulin pump– Safe and reliable method for satisfying basal insulin needs in pregnant

patients with gestational diabetes mellitus (GDM), T2DM, or T1DM1,2

• CSII may need to be combined with CGM for optimal glycemic control in T1DM1

– Can be used to effectively mimic physiologic insulin secretion2

– No significant difference in glycemic control for pregnancy outcomes with CSII versus multiple-dose insulin (MDI) therapy3

– Can help address daytime or nocturnal hypoglycemia or a prominent dawn phenomenon4

• Insulin aspart and lispro are the standard of care for CSII5

• Disadvantages of CSII: – Complexity–requires counseling and training – Cost– Potential for insulin pump failure/user error or infusion site problems2,4

1. AACE. Endocr Pract. 2011;17(2):1-53. 2. Castorino K et al. Curr Diab Rep, 2012;12:53-59.3. Hod M. Jovanovic L. Int J Clin Pract, 2010;64(166):47-52. 4. Kitzmiller JL, et al. Diabetes Care. 2008;31(5):1060-79.

5. Castorino K, Jovanovic L. Clin Chem. 2011;57(2):221-30.

Diabetes in Pregnancy: Hypoglycemia

Pathophysiology

May be related to

fetal absorption of glucose from the maternal bloodstream

via the placenta,

particularly during periods

of maternal fasting

Risk Factors

History of severe hypoglycemia

before pregnancy

Impaired hypoglycemia

awareness

Longer duration of diabetes

A1C ≤6.5% at first pregnancy

visit

High daily insulin dosage1

Causes of Iatrogenic

Hypoglycemia

Administration of too much insulin

or other anti-hyperglycemic

medication

Skipping a meal

Exercising more than usual2,3

Clinical Consequences

Signs of hypoglycemia:

anxiety, confusion, dizziness,

headache, hunger, nausea,

palpitations, sweating, tremors, warmth, weakness4

Risks of hypoglycemia: coma, traffic

accidents, death1,5

Severe hypoglycemia can lead to maternal

seizures or hypoxia

Management

Inform patients of increased risk of

severe hypoglycemia during early pregnancy4

Educate patients on

hypoglycemia prevention:

Frequent SMBGRegular meal

timing Accurate

medication administration

Careful management of

exercise programs4

1. Mathiesen ER, et al. Endocrinol Metab Clin N Am. 2011;40:727-738. 2. Inturrisi M, et al. Endocrinol Metab Clin N Am. 2011;40:703-26. 3. Jovanovic L, et al. Mt Sinai J Med. 2009;76(3):269-80. 4. Kitzmiller JL, et al. Diabetes Care. 2008;31(5):1060-79.

5. Hod M. Jovanovic L. Int J Clin Pract. 2010;64(166):47-52.

Diabetes in Pregnancy: Hypoglycemia Treatment

Suspected or confirmed

hypoglycemia (blood glucose <60 mg/dL via

SMBG)

Severe hypoglycemia (patient cannot

swallow)

1 mg glucagon injected

subcutaneously; request emergency

assistance1

Mild to moderate

hypoglycemia (patient can

swallow)

Preferred treatment: 15-20 g glucose1,2

Alternative treatments include

fast-acting carbohydrates

(eg, 8 oz nonfat milk, 4 oz juice)1

15-minutes: recheck SMBG

Hypoglycemia resolved (normal SMBG

confirmed)

Snack or meal should

be consumed to

prevent recurrence1

Hypoglycemia not resolved

Repeat treatment

1. Jovanovic L, et al. Mt Sinai J Med. 2009;76(3):269-80. 2. Kitzmiller JL, et al. Diabetes Care. 2008;31(5):1060-79.

Diabetes in Pregnancy:Physical Activity

• Unless contraindicated, physical activity should be

included in a pregnant woman’s daily regimen

• Regular moderate-intensity physical activity (eg, walking)

can help to reduce glucose levels in patients with GDM1,2

• Other appropriate forms of exercise during pregnancy:– Cardiovascular training with weight-bearing, limited to the upper

body to avoid mechanical stress on the abdominal region3

1. Castorino K, Jovanovic L. Clin Chem. 2011;57(2):221-30. 2. ADA. Diabetes Care. 2004;27(suppl 1):S88-90. 3. Jovanovic L, et al. Mt Sinai J Med. 2009;76(3):269-80.

Diabetes in Pregnancy: Weight Gain

• Patient’s prepregnancy BMI is used to determine goals for healthy weight gain1

• Independent of maternal glucose levels, higher maternal BMI has been associated with increased risk of: – Caesarean delivery

– Infant birth weight >90th percentile

– Cord-blood serum C-peptide >90th percentile2

• Evidence supports a goal of minimal weight gain during pregnancy for obese women1

• Patients should be advised to achieve weight objectives by maintaining a balanced diet and exercising regularly1

1. Castorino K, Jovanovic L. Clin Chem. 2011;57(2):221-30. 2. Metzger BE, et al. BJOG 2010;117:575-584.

Diabetes in Pregnancy: Labor and Delivery

• Counsel women on diabetes management during labor and delivery1

• During the 4-6 hours prior to delivery, there is increased risk of transient neonatal hypoglycemia1

• Labor and delivery in women with insulin-dependent type 1 diabetes should be managed by an endocrinologist or a diabetes specialist1

• Blood glucose levels should be monitored closely during labor to determine patient’s insulin requirements– Most women with gestational diabetes mellitus who are receiving insulin

therapy will not require insulin once labor begins1

1. Castorino K, Jovanovic L. Clin Chem. 2011;57(2):221-30.

Diabetes in Pregnancy: Psychological Issues

• The demands of diabetes management can have a substantial effect on pregnancy1

• Individualized psychosocial interventions are likely to help improve both pregnancy outcomes and patient quality of life1

– Include specialists in the psychological aspects of diabetes as part of the multidisciplinary healthcare team

– Healthcare teams can help manage patients’ stress and anxiety before and during pregnancy

– Identify and address barriers to effective diabetes management, such as fear of hypoglycemia and an inadequate social support network

1. Snoek SJ, et al. Psychology in Diabetes Care. 2nd Ed. West Sussex, England: John Wiley & Sons Inc., 2005:54.2. Jovanovic L, et al. Mt Sinai J Med. 2009;76(3):269-80.

Diabetes in Pregnancy: Postpartum and Lactation

• Metformin and glyburide are secreted into breast milk and are therefore contraindicated during lactation1

• Breastfeeding plus insulin therapy may lead to severe hypoglycemia1

– Greatest risk is in women with T1DM– Preventive measures are: reduce basal insulin dosage and/or

carbohydrate intake prior to breastfeeding

• Bovine-based infant formulas are linked to increased risk of T1DM1

– Avoid in offspring of women with a genetic predisposition for diabetes– Soy-based products are a potential substitute

1. Castorino K, Jovanovic L. Clin Chem. 2011;57(2):221-30.