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DIABETES IN PREGNANCY:
MANAGEMENT
Dr . Mouna Dakar
ALL DIABETES IS NOT THE SAME
• Diabetes in pregnancy ≠ Diabetes outside of
pregnancy
Outside of pregnancy goals are :
To prevent complications of cardiovascular
disease
blindness
neuropathy
renal failure
ALL DIABETES IS NOT THE SAME
During pregnancy – goals are:
Prevent macrosomia
Prevent fetal death
Prevent other fetal complications
THIS MEANS YOU CANT TREAT THEM THE SAME
During pregnancy
• more frequent visits when not controlled
• stricter glycemic goals
DIABETES IN PREGNANCY: MANAGEMENT
APPROACHES
• Early referral to a specialist is • Individualized treatment plans,
essential1
involving a combination of:
• 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 pregnancy 2
• Glucose monitoring
• Medical nutrition therapy (MNT)
• Pharmacotherapy
• Exercise
• Weight management strategies
• 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.
CONTROL OF MATERNAL GLYCEMIA
(TARGET PLASMA GLUCOSE LEVELS)
• Fasting
• 60-90 mg/dl
• Preprandial
• 60-105 mg/dl
• 1 hr after meals
• <140 mg/dl
• 2 hr after meals
• <120 mg/dl;
GLUCOSE MONITORING
• Daily SMBG superior to intermittent monitoring
• Fasting blood sugar
• Post prandial sugars most predictive of macrosomia .
The most difficult glucose to control- post
breakfast(dawn phenomenon) most predictive of fetal
demise
• Verify glucometer with your facility’s lab
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 bed 3
•
Disadvantages include:
• Potential for human error or inconsistencies in performing SMBG and/or selfreporting
• Partial glucose profile from intermittent readings; hyper- or hypoglycemic episodes
may go undetected 4
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:
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 wall 1,3
• 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
2.
1. AACE. Endocr Pract. 2010;16(5):1-16.
Chitayat, L, et al. Diabetes Technology & Therapeutics. 2009;11:S105-111.
MANAGEMENT
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.
MEDICAL NUTRITION THERAPY(MNT)
• Goal: to provide calories and nutrients to sustain
pregnancy, but does not cause post-prandial
hyperglycemia
GDM AND MNT
• Two weeks trial of Medical Nutrition Therapy
• Pre-pregnancy BMI is a predictor of the efficacy
• If target glycemia is not achieved initiate insulin
• MNT – extra 300 calories in 2 and 3 rd trimesters
• Calories – 30 kcal/kg/day = 1800 kcal for 60 kg
• If BMI > 30; then only 25 kcal/kg/day
• 3 meals and 3 snacks – avoid hypoglycemia
• 50% of total calories as CHO, 25% protein & fat
• Low glycemic, complex CHO, fiber rich foods
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CARBOHYDRATE BUDGET
• Breakfast
1-2 carbohydrate choices
• Lunch
3-4 carbohydrate choices
• Supper
3-4 carbohydrate choices
• Snacks (1-3 )
1-2 carbohydrate choices
• Amount of CHO typically found in a 2200 calorie diet
DIET THERAPY IN GDM
• Small, frequent meals
• Avoid eating for two
• Avoid fasts and feasts
• Avoid health drinks
• Eat a bedtime snack
TIPS FOR DIET MANAGEMENT
• Small breakfast
• Mid morning snack
• High protein lunch
• Mid afternoon snack
• Usual dinner
• Bed time snack
WHEN TO INITIATE PHARMACOTHERAPY
• GDM A1 to A2
• >2 values exceed goal in 1 to 2 weeks
• FBS >95
• 2 hour PP>120
• Fetal abdominal circumference >70% at 29-33 wks
(Buchanan diabetes care 1998)
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.
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
Rapid-acting (bolus)
15 min
60 min
2 hrs
Start of each meal
Regular
insulin
Intermediate-acting
60 min
2-4 hrs
6 hrs
60-90 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
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.
INSULIN THERAPY LISPRO(HUMALOG)
• Rapid Acting-good for pre-meals!
• Onset-15min
• Peak-30-90min
• Duration-3-5 hours
• Little antibody formation; more effective than regular
insulin
• Disadvantages: expensive , once thought to increase
risk for proliferative retinopathy
INSULIN THERAPY
NPH
• Intermediate Acting Insulin
• Onset
1-2 hours
• Peak
4-8 hours
• Duration 12 hours
• Good for HS to Fasting window
• May add in Am to cover midday
LANTUS(GLARGINE-DNA ORIGIN)
• Long acting
• Once a day insulin injection
• No peak
• Steady release of insulin
• Acidic pH 4. After SQ injection it is neutralized forming
micro precipitates.
• Cannot be mixed with any other insulin
• Category C
INSULIN TOTAL DAILY DOSE REGIMEN
• 1st trimester
0.7 u/kg
• 2nd trimester
0.8u/kg
• 3rd trimester
1.0u/kg
• Dose range 0.25u/kg to 1.0u/kg
********INSULIN THERAPY –DAILY BREAKDOWN
LISPRO COVERAGE
• TDD x 40%
Pre Breakfast
• TDD x 30%
Pre Lunch
• TDD x 20 %
Pre Dinner
• TDD x 10%
Bedtime
• NPH is added for coverage at bedtime
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 rapidacting 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.
2.
Castorino K, Jovanovic L. Clin Chem. 2011;57(2):221-30.
Kitzmiller JL, et al. Diabetes Care. 2008;31(5):1060-79.
INSULIN REGIMEN
• If MNT fails after 2 - 4 weeks of trial
• Initiate Insulin + Continue MNT
• Dose: 0.7, 0.8 and 0.9 u/kg – 1, 2 & 3 trim.
• Eg. 1st trim – 64 kg = 0.7 x 64 = 45 units
• Give 2/3 before BF = 30 units of 30:70 mix
• Give 1/3 before supper = 15 u of 50:50 mix
• Increase total dose by 2-4 units based on BG
• After BG levels stabilize – monitor till term
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BEWARE OF VICIOUS CYCLE
BG
Appetite
Wt Gain
Insulin
resistance
PHARMACOLOGIC THERAPY: CSII
• Continuous subcutaneous insulin infusion (CSII or
insulin pump therapy), consists of a syringe or
cartridge filled with short- or rapid-acting insulin that
is connected to a catheter inserted into subcutaneous
tissue.
• The pump is programmed to dispense a continuous
infusion of basal insulin.
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 T1DM 1
• 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 CSII 5
• 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.
HOW BIG IS THE PROBLEM?
MANAGEMENT OF GDM/TYPE 2
ORAL AGENTS
• First line glyburide ( not used in Type 1)
• Max dose 20mg/day
• Usual dose 5-10mg targeted for time when glucose
abnormal ( there is a 2.5mg dose)
• It’s a sulfonylurea - don’t use in patients with sulfa
allergy
• Long tail –most common side effect is hypoglycemia
ORAL HYPOGLYCEMIC AGENTS
GLYBURIDE
• An effective alternative to insulin in the treatment of
gestational diabetes .
• 30 –40 % failure rate in some series of studies
• Patients prefer oral agents rather than injections!
• Other agents Metformin( biguanide)
MANAGEMENT OF GDM/TYPE 2
ORAL AGENTS
• Metformin – insulin sensitizer
• Maximum dose studied 2000mg/day but have seen
patients on up to 2500.
• Crosses the placenta in appreciable amounts
• Doesn’t cause hypoglycemia
• Can be combined with glyburide
• Most common side effect is GI upset
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
Placenta
Classification
Notes
Metformin
Yes
Category B1
Glyburide
Minimal
transfer
Metformin and glyburide may be insufficient to
maintain normoglycemia at all times, particularly
during postprandial periods2
•
Some formulations
category B, others
Due to efficacy and safety
concerns, the ADA does not recommend oral
category C1,5,6
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.
PHARMACOLOGIC THERAPY: GDM (CONTINUED)
• Oral antidiabetes medications have been studied
during pregnancy but are not yet approved for use.
• Both glyburide and metformin have been used
successfully under research protocols.
GDM AND DELIVERY
• Delivery until 40 weeks is not recommended
• Delivery before 39th week – assess the pulmonary
maturity by phosphatase test on amniocentesis fluid
• C - Section may be needed (25 -30%)
• Be prepared for the neonatal complications
• Assess the mother after delivery for glycemia
• May need to continue insulin for a few days
• Pre-gestational DM–Insulin (30% less) or OAD
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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 begins 1
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.
MAJOR GOALS
• Manage all diabetes patients with a team approach
• Major Goals:To prevent
Macrosomia,hyperbilirubenemia,birth trauma,neonatal
hypoglycemia in the baby
• To prevent: operative deliveries(including –vacuum
extraction,forceps delivery,and cesarean
deliveries),genital trauma,and prevent preeclampsia in
the mother