2 Diabetes in Pregnancy: Management Goals Provide preconception care for women with preexisting T1DM or T2DM or a history of GDMEducate patients to maintain adequate nutrition and glucose control before conception, during pregnancy, and postpartum1Close to normal glycemic control prior to and throughout pregnancy offers substantial benefit for both mother and child2Maintenance of normoglycemia prior to and through the first trimester results in a complication risk close to that of women without diabetes3For all glucose management protocols, AACE recommendations stress patient safety as the first priority1,41. 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 IncrementPatients with GDMPatients with Preexisting T1DM or T2DMPreprandial, premeal≤95 mg/dL (5.3 mmol/L)Premeal, bedtime, and overnight glucose:60-99 mg/dL ( mmol/L)Postprandial, post-meal1-hour post-meal: ≤140 mg/dL (7.8 mmol/L) or2-hour post-meal: ≤120 mg/dL (6.7 mmol/L)Peak postprandial glucose mg/dL( mmol/L)A1CA1C ≤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 complications1,2Glucose IncrementPatients With Gestational Diabetes Mellitus (GDM)1Patients With Preexisting T1DM or T2DM1,2Preprandial, premeal≤90 mg/dL (5.0 mmol/L)1,2Postprandial, post-meal1-hour post-meal: ≤120 mg/dL (6.7 mmol/L)1,2A1CA1C <5.0%3 A1C <6.0%4LeRoith 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 pregnancy1A 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 GDM2Improvements in maternal health-related quality of life2ADA. 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 infants1,2Preconception careRenal impairment, cardiac disease, neuropathy3Careful evaluations at each visit1st trimester through 1st year postpartumExamine active lesions more frequently1Regular ophthalmologic examsTarget: systolic BP mmHg; diastolic BP mmHgLifestyle changes, behavior therapy, and pregnancy-safe medications (ACE inhibitors and ARBs contraindicated in pregnancy)3Hypertension management1. 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 essential1Collaborative effort among obstetrician/ midwife, endocrinologist, ophthalmologist, registered dietitian, and nurse educatorAll team members should be engaged in patient education/care prior to and throughout pregnancy2Individualized treatment plans, involving a combination of:Glucose monitoringMedical nutrition therapy (MNT)PharmacotherapyExerciseWeight management strategiesPsychological supportCastorino 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)1ADA guidelines for pregnant patients requiring insulin:SMBG ≥3 times dailyMore frequent SMBG may be required, including:2Morning fastingPremeal (breakfast, lunch, and dinner)1-hour postprandial (breakfast, lunch, and dinner)Before bed3Disadvantages include:Potential for human error or inconsistencies in performing SMBG and/or self-reportingPartial glucose profile from intermittent readings; hyper- or hypoglycemic episodes may go undetected41. 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 controlTo safely achieve target glucose levels, combine A1C with frequent self-monitoring of blood glucose (SMBG)1,2Recent research suggests weekly A1Cs during pregnancy:1SMBG alone can miss certain high glucose valuesSMBG + A1C = more complete data for glucose controlClinicians can further optimize treatment decisions with weekly A1COther 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 diabetes31. 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 period1Continuous glucose monitoring (CGM) measures glucose concentration of interstitial fluid using subcutaneous sensor tip implanted in abdominal wall1,3Identifies glycemic excursions that may go undetected with SMBG1May be recommended when patient unable to achieve target glucose levels with SMBG alone2Educational tool to improve treatment adherence4Benefits:Improved glycemic control during third trimesterReduced infant birth weightDecreased risk of infant macrosomia1,2,31. 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 devicesOwned by a health care professional1Typically implanted for 3-5 days1Data downloaded and analyzed by a health care professional1Personal CGM devicesOwned by the patientMay be implanted for longer periods (eg, several weeks)1Provide continuous feedback on glucose values, which may be read/interpreted by the patient in real time2AACE. 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 pregnancy1,2MNT is based on standard nutritional recommendations during pregnancy, with customization based on:HeightWeightNutritional assessmentLevel of glycemic control3,4,5Goals:Provide a nutritionally adequate diet for pregnancyAchieve normoglycemiaTarget Glucose Levels for Normoglycemia3Preprandial glucose ≤95 mg/dL (5.3 mmol/L)1-hour postprandial glucose ≤140 mg/dL (7.8 mmol/L) or2-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 GDMMedical nutrition therapy (MNT) and lifestyle changes can effectively manage 80% to 90% of mild GDM cases1,2MNT nutritional goals and recommendations:Choose healthy low-carbohydrate, high-fiber sources of nutrition, with fresh vegetables as the preferred carbohydrate sources4Count carbohydrates and adjust intake based on fasting, premeal, and postprandial SMBG measurements4,6Avoid sugars, simple carbohydrates, highly processed foods, dairy, juices, and most fruits4,5Eat frequent small meals to reduce risk of postprandial hyperglycemia and preprandial starvation ketosis5As pregnancy progresses, glucose intolerance typically worsens; patients may ultimately require insulin therapy1,31. 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 indicatedAACE guidelines recommend insulin as the optimal approach1Insulin therapy is required for the treatment of T1DM during pregnancy2Metformin and the sulfonylurea glyburide are the 2 most commonly prescribed oral antihyperglycemic agents during pregnancy1,2Due to efficacy and safety concerns, the ADA does not recommend oral antihyperglycemic agents for gestational diabetes mellitus (GDM) or preexisting T2DM3,4MedicationCrosses PlacentaClassificationNotesMetforminYesCategory B1Metformin and glyburide may be insufficient to maintain normoglycemia at all times, particularly during postprandial periods2GlyburideMinimal transferSome formulations category B, others category C1,5,61. 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 EducationInsulin administration, dietary modifications in response to self-monitoring of blood glucose (SMBG), hypoglycemia awareness and management1Basal InsulinIntermediate- or long-acting insulin administered by injection, orRapid-acting insulin administered by insulin pump2,3Postprandial HyperglycemiaRecommended approach: rapid-acting insulin analogues2Alternative 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)3Insulin OptionsInsulin NPH: safe intermediate alternative (category B)2Insulin detemir: safe long-acting alternative (category B)2,3Lispro and aspart: safe rapid-acting insulin analogues (category B)2,3Insulin glargine: frequently prescribed in pregnancy; however, safety in pregnancy has not been definitively established (category C)2,31. 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 InsulinGlucose Levels for Insulin Initiation in GDM1Fasting 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 Pregnancy1NameTypeOnsetPeak EffectDurationRecommended Dosing IntervalAspartRapid-acting (bolus)15 min60 min2 hrsStart of each mealLisproRegular insulinIntermediate-acting2-4 hrs6 hrs60-90 minutes before mealNPHIntermediate-acting (basal)4-6 hrs8 hrsEvery 8 hoursDetemirLong-acting (basal)n/a12 hrsEvery 12 hoursFollowing a positive pregnancy test, patients with preexisting diabetes being treated with insulin or oral antihyperglycemic medications should be transitioned to one of the above options21. 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 Postpartum1Weeks gestationTotal 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 frameFrom weeks 14 through 35 of gestation, insulin requirements typically increase steadilyAfter 35 weeks gestation, insulin requirements may level off or even decline2Obese patients may require higher insulin dosages than non-obese individuals2Castorino 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 pumpSafe and reliable method for satisfying basal insulin needs in pregnant patients with gestational diabetes mellitus (GDM), T2DM, or T1DM1,2CSII may need to be combined with CGM for optimal glycemic control in T1DM1Can be used to effectively mimic physiologic insulin secretion2No significant difference in glycemic control for pregnancy outcomes with CSII versus multiple-dose insulin (MDI) therapy3Can help address daytime or nocturnal hypoglycemia or a prominent dawn phenomenon4Insulin aspart and lispro are the standard of care for CSII5Disadvantages of CSII:Complexity–requires counseling and trainingCostPotential for insulin pump failure/user error or infusion site problems2,4AACE. 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 PathophysiologyMay be related to fetal absorption of glucose from the maternal bloodstream via the placenta, particularly during periods of maternal fastingRisk FactorsHistory of severe hypoglycemia before pregnancyImpaired hypoglycemia awarenessLonger duration of diabetesA1C ≤6.5% at first pregnancy visitHigh daily insulin dosage1Causes of Iatrogenic HypoglycemiaAdministration of too much insulin or other anti-hyperglycemic medicationSkipping a mealExercising more than usual2,3Clinical ConsequencesSigns of hypoglycemia: anxiety, confusion, dizziness, headache, hunger, nausea, palpitations, sweating, tremors, warmth, weakness4Risks of hypoglycemia: coma, traffic accidents, death1,5Severe hypoglycemia can lead to maternal seizures or hypoxiaManagementInform patients of increased risk of severe hypoglycemia during early pregnancy4Educate patients on hypoglycemia prevention:Frequent SMBGRegular meal timingAccurate medication administrationCareful management of exercise programs41. 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 assistance1Mild to moderate hypoglycemia (patient can swallow)Preferred treatment: g glucose1,2Alternative treatments include fast-acting carbohydrates (eg, 8 oz nonfat milk, 4 oz juice)115-minutes: recheck SMBGHypoglycemia resolved (normal SMBG confirmed)Snack or meal should be consumed to prevent recurrence1Hypoglycemia not resolvedRepeat treatment1. 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 regimenRegular moderate-intensity physical activity (eg, walking) can help to reduce glucose levels in patients with GDM1,2Other appropriate forms of exercise during pregnancy:Cardiovascular training with weight-bearing, limited to the upper body to avoid mechanical stress on the abdominal region31. 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 gain1Independent of maternal glucose levels, higher maternal BMI has been associated with increased risk of:Caesarean deliveryInfant birth weight >90th percentileCord-blood serum C-peptide >90th percentile2Evidence supports a goal of minimal weight gain during pregnancy for obese women1Patients should be advised to achieve weight objectives by maintaining a balanced diet and exercising regularly11. 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 delivery1During the 4-6 hours prior to delivery, there is increased risk of transient neonatal hypoglycemia1Labor and delivery in women with insulin-dependent type 1 diabetes should be managed by an endocrinologist or a diabetes specialist1Blood glucose levels should be monitored closely during labor to determine patient’s insulin requirementsMost women with gestational diabetes mellitus who are receiving insulin therapy will not require insulin once labor begins11. 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 pregnancy1Individualized psychosocial interventions are likely to help improve both pregnancy outcomes and patient quality of life1Include specialists in the psychological aspects of diabetes as part of the multidisciplinary healthcare teamHealthcare teams can help manage patients’ stress and anxiety before and during pregnancyIdentify and address barriers to effective diabetes management, such as fear of hypoglycemia and an inadequate social support network1. 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 lactation1Breastfeeding plus insulin therapy may lead to severe hypoglycemia1Greatest risk is in women with T1DMPreventive measures are: reduce basal insulin dosage and/or carbohydrate intake prior to breastfeedingBovine-based infant formulas are linked to increased risk of T1DM1Avoid in offspring of women with a genetic predisposition for diabetesSoy-based products are a potential substitute1. Castorino K, Jovanovic L. Clin Chem. 2011;57(2):