1. Diabetes in Pregnancy
Management

2. 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): Mathiesen ER, et al. Endocrinol Metab Clin N Am. 2011;40: Castorino K, Jovanovic L. Clin Chem. 2011;57(2): ADA. Diabetes Care. 2013;36(suppl 1):S11-S66.

3. 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 ( 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 mg/dL
( mmol/L)
A1C
A1C ≤6.0%   
AACE. Endocr Pract. 2011;17(2):1-53.
ADA. Diabetes Care. 2013;36(suppl 1):S11-66.

4. Glycemic Targets During Pregnancy: Expert Recommendations
Some experts recommend more stringent goals (in particular, for patients on insulin therapy) to prevent maternal and fetal complications1,2
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
LeRoith D, et. al. Endocrinol Metab Clin N Am. 2011;40(1): xii-919.
Castorino K et al. Curr Diab Rep, 2012;12:53-59.
L. Jovanovic; personal communication.
AACE. Endocr Pract. 2011;17(2):1-53.

5. 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
ADA. Diabetes Care. 2013;36(suppl 1):S11-S66.
2. Crowther CA, et al. N Engl J Med. 2005;352(24): Epub 2005 Jun 12.

6. 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 evaluations at each visit
1st trimester through 1st year postpartum
Examine active lesions more frequently1
Regular ophthalmologic exams
Target: systolic BP mmHg; diastolic BP 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): Jovanovic L, et al. Diabetes Care. 2011;34(1): Jovanovic L, et al. Mt Sinai J Med. 2009;76(3): ADA. Diabetes Care. 2013;36(suppl 1):S11-S66.

7. Diabetes in Pregnancy: Management Approaches
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
Castorino K, Jovanovic L. Clin Chem. 2011;57(2):
2. Mathiesen ER, et al. Endocrinol Metab Clin N Am. 2011;40:

8. 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): ADA. Diabetes Care. 2013;36(suppl 1):S11-S66.
3. Castorino K, Jovanovic L. Clin Chem. 2011;57(2): Chitayat, L, et al. Diabetes Technol Ther. 2009;11:S

9. 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): Castorino K, Jovanovic L. Clin Chem. 2011;57(2): Lowe LP, et al. Diabetes Care. 2012;35:

10. 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): Castorino K, Jovanovic L. Clin Chem. 2011;57(2): Chitayat, L, et al. Diabetes Technology & Therapeutics. 2009;11:S AACE. Endocr Pract. 2010;16(5):1-16.

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

12. Medical Nutrition Therapy (MNT)
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
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)
1. Castorino K, Jovanovic L. Clin Chem. 2011;57(2): Kitzmiller JL, et al. Diabetes Care. 2008;31(5): Jovanovic L, et al. Mt Sinai J Med. 2009;76(3): ADA. Diabetes Care. 2004;27(suppl 1):S National Academy of Sciences, Institute of Medicine, Food and Nutrition Board, Committee on Nutritional Status in Pregnancy and Lactation, Nutrition During Pregnancy: Accessed: April 26, 2012.

13. 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:S ADA. Diabetes Care. 2013;36(suppl 1):S ADA. Diabetes Care. 2004;27(suppl 1):S Castorino K, Jovanovic L. Clin Chem. 2011;57(2): Jovanovic L, et al. Mt Sinai J Med. 2009;76(3): Mathiesen ER, et al. Endocrinol Metab Clin N Am. 2011;40:

14. 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
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
1. AACE. Endocr Pract. 2011;17(2): Castorino K, Jovanovic L. Clin Chem. 2011;57(2): ADA. Diabetes Care. 2004;27(suppl 1):S Jovanovic L, et al. Mt Sinai J Med. 2009;76(3): Micronase PI. Pifizer. Division of Pifizer, NY, NY, Diabeta PI. Sanofi-Aventis U.S. Bridgewater, NJ, 2009.

15. 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 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): AACE. Endocr Pract. 2011;17(2): Castorino K, Jovanovic L. Clin Chem. 2011;57(2): ADA. Diabetes Care. 2004;27(suppl 1):S88-90.

16. Glucose Levels for Insulin Initiation in GDM1
Gestational Diabetes Mellitus (GDM): Initiation of Insulin
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)
1. ADA. Diabetes Care. 2004;27(suppl 1):S88-90.

17. Diabetes in Pregnancy: Insulin
Insulin Options Shown to Be Safe During Pregnancy1
Name
Type
Onset
Peak Effect
Duration
Recommended Dosing Interval
Aspart
Rapid-acting (bolus)
15 min
60 min
2 hrs
Start of each meal
Lispro
Regular insulin
Intermediate-acting
2-4 hrs
6 hrs
60-90 minutes before meal
NPH
Intermediate-acting (basal)
4-6 hrs
8 hrs
Every 8 hours
Detemir
Long-acting (basal)
n/a
12 hrs
Every 12 hours
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
1. Castorino K, Jovanovic L. Clin Chem. 2011;57(2): Kitzmiller JL, et al. Diabetes Care. 2008;31(5):

18. 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
Castorino K, Jovanovic L. Clin Chem. 2011;57(2):
Kitzmiller JL, et al. Diabetes Care. 2008;31(5):

19. 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
AACE. Endocr Pract. 2011;17(2): Castorino K et al. Curr Diab Rep, 2012;12: Hod M. Jovanovic L. Int J Clin Pract, 2010;64(166): Kitzmiller JL, et al. Diabetes Care. 2008;31(5):
5. Castorino K, Jovanovic L. Clin Chem. 2011;57(2):

20. 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 SMBG
Regular meal timing
Accurate medication administration
Careful management of exercise programs4
1. Mathiesen ER, et al. Endocrinol Metab Clin N Am. 2011;40: Inturrisi M, et al. Endocrinol Metab Clin N Am. 2011;40: Jovanovic L, et al. Mt Sinai J Med. 2009;76(3): Kitzmiller JL, et al. Diabetes Care. 2008;31(5): Hod M. Jovanovic L. Int J Clin Pract. 2010;64(166):47-52.

21. 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: 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): Kitzmiller JL, et al. Diabetes Care. 2008;31(5):

22. 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): ADA. Diabetes Care. 2004;27(suppl 1):S Jovanovic L, et al. Mt Sinai J Med. 2009;76(3):

23. 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): Metzger BE, et al. BJOG 2010;117:

24. 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):

25. 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: Jovanovic L, et al. Mt Sinai J Med. 2009;76(3):

26. 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):