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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
Patients with
Glucose
Patients with GDM Preexisting T1DM or
Increment
T2DM
Preprandial, 95 mg/dL (5.3 mmol/L) Premeal, bedtime, and
premeal overnight glucose:
60-99 mg/dL
(3.4-5.5 mmol/L)

Postprandial, 1-hour post-meal: 140 mg/dL Peak postprandial


post-meal (7.8 mmol/L) or glucose 100-129 mg/dL
2-hour post-meal: 120 mg/dL (5.5-7.1 mmol/L)
(6.7 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
Some experts recommend more stringent goals
(in particular, for patients on insulin therapy)
to prevent maternal and fetal complications1,2
Patients With
Glucose Patients With Gestational
Preexisting T1DM or
Increment Diabetes Mellitus (GDM)1
T2DM1,2
Preprandial, 90 mg/dL (5.0 mmol/L)1,2
premeal
Postprandial, 1-hour post-meal: 120 mg/dL (6.7 mmol/L)1,2
post-meal
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.
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
Preconception care dramatically reduced morbidity and mortality
in both mothers and infants1,2

Careful evaluations Renal impairment, cardiac disease,


at each visit neuropathy3

Regular 1st trimester through 1st year postpartum


ophthalmologic exams Examine active lesions more frequently1

Target: systolic BP 110-129 mmHg; diastolic


BP 65-79 mmHg
Hypertension
Lifestyle changes, behavior therapy, and
management pregnancy-safe medications (ACE inhibitors
and ARBs contraindicated in pregnancy)3

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.
Diabetes in Pregnancy:
Management Approaches
Early referral to a Individualized treatment
specialist is essential1 plans, involving a
Collaborative effort combination of:
among obstetrician/ Glucose monitoring
midwife, endocrinologist, Medical nutrition therapy
ophthalmologist, (MNT)
registered dietitian, and Pharmacotherapy
nurse educator
Exercise
All team members should
be engaged in patient Weight management
education/care prior to and strategies
throughout pregnancy2 Psychological support

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.
Medical Nutrition Therapy (MNT)
Refer patients for nutritional Goals:
counseling with registered Provide a nutritionally adequate
dietitian familiar with diet for pregnancy
pregnancy1,2 Achieve normoglycemia
MNT is based on standard Target Glucose Levels for
nutritional recommendations Normoglycemia3
during pregnancy, with
customization based on: Preprandial glucose
95 mg/dL (5.3 mmol/L)
Height
1-hour postprandial glucose
Weight
140 mg/dL (7.8 mmol/L) or
Nutritional assessment
2-hour postprandial glucose
Level of glycemic control3,4,5
120 mg/dL (6.7 mmol/L)

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.
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

Medication Crosses Classification Notes


Placenta
Metformin Yes Category B1 Metformin and glyburide may be
insufficient to maintain normoglycemia at
Glyburide Minimal Some formulations
all times, particularly during postprandial
transfer category B, others
periods2
category C1,5,6

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.
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.
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.


Diabetes in Pregnancy: Insulin
Insulin Options Shown to Be Safe During Pregnancy1
Peak Recommended
Name Type Onset Duration
Effect Dosing Interval
Rapid-acting Start of each
Aspart 15 min 60 min 2 hrs
(bolus) meal
Rapid-acting Start of each
Lispro 15 min 60 min 2 hrs
(bolus) meal
Regular Intermediate- 60-90 minutes
60 min 2-4 hrs 6 hrs
insulin acting before meal
Intermediate-
NPH 2 hrs 4-6 hrs 8 hrs Every 8 hours
acting (basal)
Long-acting
Detemir 2 hrs n/a 12 hrs Every 12 hours
(basal)
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):221-30.
2. Kitzmiller JL, et al. Diabetes Care. 2008;31(5):1060-79.
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:
Complexityrequires 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
Causes of
Clinical
Pathophysiology Risk Factors Iatrogenic Management
Consequences
Hypoglycemia

Inform patients of
History of severe increased risk of
Administration of Signs of severe
hypoglycemia too much insulin or hypoglycemia: hypoglycemia
before other anti- anxiety, confusion, during early
May be pregnancy hyperglycemic dizziness, pregnancy4
related to fetal medication headache, hunger,
nausea,
absorption of Impaired palpitations, Educate patients
glucose from hypoglycemia sweating, tremors, on
the maternal awareness warmth, weakness4 hypoglycemia
prevention:
bloodstream Skipping a meal
via the Frequent SMBG
Longer duration Risks of Regular meal
placenta, of diabetes hypoglycemia:
particularly timing
coma, traffic
during periods accidents, death1,5 Accurate
of maternal A1C 6.5% at medication
first pregnancy administration
fasting visit Exercising more
Severe
hypoglycemia can Careful
than usual2,3 lead to maternal management of
High daily insulin seizures or exercise
dosage1 hypoxia 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
Hypoglycemia Snack or
1 mg glucagon resolved meal should
Severe (normal
injected be consumed
hypoglycemia SMBG
subcutaneously; to prevent
(patient cannot confirmed)
swallow)
request emergency recurrence1
Suspected or assistance1
confirmed
hypoglycemia
(blood glucose Preferred treatment:
<60 mg/dL via 15-20 g glucose1,2
SMBG) Mild to 15-minutes:
moderate recheck
Alternative SMBG
hypoglycemia treatments include
(patient can fast-acting
swallow) carbohydrates
(eg, 8 oz nonfat milk,
4 oz juice)1 Repeat
Hypoglycemia treatment
not resolved

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 womans 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
Patients 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 patients 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.

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