Management of Diabetes in Pregnancy 1 Management of
Management of Diabetes in Pregnancy 1 Management of Diabetes in Pregnancy PRECONCEPTION CARE 2 Preconception Care for Women With Established T1D or T2D All Women of ChildBearing Age Provide counseling on effective contraception for all who wish to avoid pregnancy Evaluate and treat diabetesrelated complications Women Seeking to Become Pregnant Review risks of uncontrolled diabetes during pregnancy Provide counseling on medications contraindicated during pregnancy Statins, angiotensinconverting-enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), and most non-insulin antihyperglycemic agents Handelsman YH, et al. Endocr Pract. 2015;21(suppl 1):1-87. ADA. Diabetes Care. 2015;38(suppl 1):S77-S79.
3 Potential Contraindications to Pregnancy in Women with Established Diabetes Ischemic heart disease Untreated active proliferative retinopathy Renal insufficiency Severe gastroenteropathy Jovanovic L, et al. Mt Sinai J Med. 2009;76:269-280. 4 Preconception Glucose Control for Women with T1D or T2D Preconception A1C goal ADA AACE <7.0%* <6.5%* *If achievable without hypoglycemia
Handelsman YH, et al. Endocr Pract. 2015;21(suppl 1):1-87. ADA. Diabetes Care. 2015;38(suppl 1):S77-S79. 5 Management of Diabetes in Pregnancy POST-CONCEPTION CARE 6 Diabetes in Pregnancy: Management Goals Educate patients to maintain adequate nutrition and glucose control before conception, during pregnancy, and postpartum Maintain close-to-normal glycemic control prior to and throughout pregnancy Complication risk close to that of women without diabetes Weekly A1C monitoring may be helpful to maintain goals (erythrocyte lifespan is 90 days during pregnancy) Patient safety is first priority Handelsman YH, et al. Endocr Pract. 2015;21(suppl 1):1-87. ADA. Diabetes Care. 2015;38(suppl 1):S77-S79. 7 Glucose Targets for Pregnant Women: AACE Recommendations Condition Treatment Goal
GDM Preprandial glucose, mg/dL 95* 1-Hour PPG, mg/dL 140* 2-Hour PPG, mg/dL 120* Preexisting T1D or T2D Premeal, bedtime, and overnight glucose, mg/dL Peak PPG, mg/dL A1C 60-99* 100-129* 6.0%* *Provided target can be safely achieved. FPG, fasting plasma glucose; GDM, gestational diabetes mellitus; PPG, postprandial glucose, T1D, type 1 diabetes; T2D, type 2 diabetes. Handelsman YH, et al. Endocr Pract. 2015;21(suppl 1):1-87. 8 Glycemic Targets During Pregnancy: Expert Recommendations Some experts recommend more stringent goals (in particular, for patients on insulin therapy) to prevent maternal and fetal complications
Glucose Increment Preprandial, premeal Postprandial, post-meal A1C GDM Preexisting T1D or T2D 90 mg/dL (5.0 mmol/L) 1-hour post-meal: 120 mg/dL (6.7 mmol/L) A1C <5.0% A1C <6.0% LeRoith D, et. al. Endocrinol Metab Clin N Am. 2011;40: xii-919. Castorino K et al. Curr Diabetes Rep, 2012;12:53-59. 9 Infant Outcomes With Tight Glucose Control During Pregnancy Intervention n (%) Routine care n (%) Any serious perinatal complication* 7 (1)
Shoulder dystocia Admission to neonatal nursery Jaundice requiring phototherapy Favors tight control Favors routine care Adjusted relative risk (95% CI) P value 23 (4) 0.33 (0.14-0.75) 0.01 7 (1) 16 (3) 0.46 (0.19-1.10) 0.08
357 (71) 321 (61) 1.13 (1.03-1.23) 0.01 44 (9) 48 (9) 0.93 (0.63-1.37) 0.72 0.00 1.00 2.00 *Death, shoulder dystocia, bone fracture, or nerve palsy. Crowther CA, et al. N Engl J Med. 2005;352:2477-2486. 10 Diabetes in Pregnancy: Avoiding Complications Preconception care Advances in diagnosis and treatment have dramatically reduced morbidity and mortality in both mothers and infants
Careful evaluations at each visit Renal impairment, cardiac disease, neuropathy Regular ophthalmologic exams Hypertension management 1st trimester through 1st year postpartum Examine active lesions more frequently 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) ACE, angiotensin-converting enzyme; ARB, angiotensin II receptor blocker; BP, blood pressure. Handelsman YH, et al. Endocr Pract. 2015;21(suppl 1):1-87. ADA. Diabetes Care. 2015;38(suppl 1):S77-S79. Jovanovic L, et al. Diabetes Care. 2011;34:53-54. 11 Diabetes in Pregnancy: Management Approaches Early referral to a specialist is essential 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 Castorino K, Jovanovic L. Clin Chem. 2011;57:221-230. Mathiesen ER, et al. Endocrinol Metab Clin N Am. 2011;40:727-738. Individualized treatment plans, involving a combination of: Glucose monitoring Medical nutrition therapy (MNT) Pharmacotherapy Exercise Weight management Psychological support 12 Glucose Monitoring in Pregnant Women with Diabetes: SMBG Recommendations Caveats and Limitations Insulin-requiring pregnant patients should perform SMBG 3 times daily
Potential for human error or inconsistencies in performing SMBG and/or self-reporting Hyper- or hypoglycemic episodes may go undetected when readings are intermittent Morning fasting Premeal (breakfast, lunch, and dinner) 1-hour postprandial (breakfast, lunch, and dinner) Before bed SMBG is the cornerstone of glucose management during pregnancy SMBG, self-monitoring of blood glucose. Jovanovic L, et al. Diabetes Care. 2011;34:53-54. Castorino K, Jovanovic L. Clin Chem. 2011;57:221-230. Chitayat, L, et al. Diabetes Technol Ther. 2009;11:S105-111. 13 Glucose Monitoring in Pregnant Women with Diabetes: A1C Recommendations Combine with SMBG to safely achieve target glucose levels Weekly A1C during pregnancy recommended SMBG alone can miss certain high glucose values
SMBG + A1C yields more complete data for glucose control Clinicians can further optimize treatment decisions with weekly A1C Caveats and Limitations HAPO study suggests OGTT may predict adverse pregnancy outcomes better than A1C in women with diabetes HAPO, Hyperglycemia and Adverse Pregnancy Outcomes; SMBG, self-monitoring of blood glucose. Jovanovic L, et al. Diabetes Care. 2011;34:53-54. Castorino K, Jovanovic L. Clin Chem. 2011;57:221-230. Lowe LP, et al. Diabetes Care. 2012;35:574-580. 14 Glucose Monitoring in Pregnant Women with Diabetes: CGM Recommendations CGM devices Measure glucose concentration of interstitial fluid using subcutaneous sensor tip implanted in abdominal wall Identify glycemic excursions that may go undetected with SMBG
Caveats and Limitations Requires specialized knowledge (provider) and patient education May be used as educational tool to improve treatment adherence CGM may be useful in patients unable to achieve target glucose levels with SMBG alone CGM, continuous glucose monitoring. Hod M, Jovanovic L. Int J Clin Pract Suppl. 2010 Feb;(166):47-52. Castorino K, Jovanovic L. Clin Chem. 2011;57:221-230. Chitayat, L, et al. Diabetes Technol Ther. 2009;11:S105-111. Blevins TC, et al. Endocr Pract. 2010;16:1-16. 15 Reduced Risk of Macrosomia With CGM Pregnant Women With T1D or T2D (N=71) 6.5 6.4 6.3 6.2 6.1 6 5.9 5.8 5.7 5.6 5.5 No CGM 6.4
6.4 P=0.1 6.1 P=0.007 5.8 No difference in A1C 8-28 28-32 32-36 70 Infants with macrosomia (%) A1C (%) CGM 60 60 50 OR: 0.36 (0.13 to 0.98) P=0.05 40
35 30 20 10 0 CGM No CGM Weeks Gestation CGM, continuous glucose monitoring; OR, odds ratio for reduced risk of macrosomia (95% confidence interval). Murphy HR, et al. BMJ. 2008;337:a1680. doi: 10.1136/bmj.a1680. 16 CGM Devices: Professional vs Personal Professional Owned by a health care professional Typically implanted for 3-5 days Data downloaded and analyzed by a health care professional Blevins TG, et al. Endocr Pract. 2010;16:1-16. Chitayat, L, et al. Diabetes Technol Ther. 2009;11:S105-S111. Personal
Owned by the patient May be implanted for longer periods (eg, several weeks) Provide continuous feedback on glucose values, which may be read/interpreted by the patient in real time 17 Medical Nutrition Therapy During Pregnancy Key recommendations Refer patients for nutritional Choose healthy low-carbohydrate, counseling with registered high-fiber sources of nutrition, with dietitian familiar with pregnancy Provide a nutritionally adequate diet for pregnancy Achieve normoglycemia Customize standard nutritional recommendations during pregnancy based on: Height Weight
Nutritional assessment Level of glycemic control fresh vegetables as the preferred carbohydrate sources Count carbohydrates and adjust intake based on fasting, premeal, and postprandial SMBG measurements Avoid sugars, simple carbohydrates, highly processed foods, dairy, juices, and most fruits Eat frequent small meals to reduce risk of postprandial hyperglycemia and preprandial starvation ketosis MNT, medical nutrition therapy. Handelsman YH, et al. Endocr Pract. 2015;21(suppl 1):1-87. ADA. Diabetes Care. 2015;38(suppl 1):S77-S79. Castorino K, Jovanovic L. Clin Chem. 2011;57:221-230. Jovanovic L, et al. Mt Sinai J Med. 2009;76:269-280. Mathiesen ER, et al. Endocrinol Metab Clin N Am. 2011;40:727-738. 18 Pharmacologic Treatment of Diabetes During Pregnancy Use insulin to treat hyperglycemia in T1D and T2D and when lifestyle measures do not control glycemia in GDM Basal insulin: NPH or insulin detemir Prandial insulin: insulin analogs preferred, but regular insulin acceptable if analogs not available Handelsman YH, et al. Endocr Pract. 2015;21(suppl 1):1-87. ADA. Diabetes Care. 2015;38(suppl 1):S77-S79.
19 Oral Antihyperglycemic Therapy During Pregnancy Medication Crosses Placenta Classification Notes Metformin Yes Category B Glyburide Minimal transfer Some formulations category B (Micronase), others category C (Diaeta)
Metformin and glyburide may be insufficient to maintain normoglycemia at all times, particularly during postprandial periods Long-term safety of these agents during pregnancy is unknown No other noninsulin antihyperglycemic agents are considered safe during pregnancy. Handelsman YH, et al. Endocr Pract. 2015;21(suppl 1):1-87. ADA. Diabetes Care. 2015;38(suppl 1):S77-S79. Poomalar GK. World J Diabetes. 2015;6:284-295. Micronase (glyburide) prescribing information. New York, NY: Pfizer Inc.; 2015. Diaeta (glyburide) prescribing information. Bridgewater, NJ: sanofi-aventis U.S. LLC; 2009. 20 Effects of Metformin Therapy During Pregnancy Metformi n treatment Insulin treatment Standard mean difference (95% CI) P value Maternal weight gain -0.47 (-0.77, -0.16)
0.003 Gestational age at delivery -0.14 (-0.25, -0.03) 0.02 Infant birth weight -0.04 (-0.17, 0.09) 0.54 - Gui J, et al. PLOS One. 2013;8(5):e64585. 21 Benefits and Risks of Metformin Therapy During Pregnancy Favors metformin Favors insulin Odds ratio (95% CI) P value 1.74 (1.13, 2.68)
0.01 0.52 (0.30, 0.90) 0.02 0.69 (0.42, 1.12) 0.13 Large for gestational age 0.78 (0.49, 1.25) 0.31 Small for gestational age 0.78 (0.48, 1.29) 0.34 Infant hypoglycemia 0.80 (0.58, 1.11) 0.19 Maternal risks Preterm birth Pregnancy-induced hypertension Preeclampsia
Infant risks Gui J, et al. PLOS One. 2013;8(5):e64585. 22 Insulin Use During Pregnancy Pregnancy Category Insulin option Notes Basal (control of fasting/preprandial glucose) NPH B Detemir B Glargine C Pump therapy with rapidacting analogs B Not formally studied in pregnancy, though frequently prescribed
Bolus (control of postprandial hyperglycemia) Aspart, lispro B Regular B Glulisine C Not studied in pregnancy Inhaled C Not studied in pregnancy Components of patient education Insulin administration Dietary modifications in response to SMBG Hypoglycemia awareness and management NPH, Neutral Protamine Hagedorn; SMBG, self-monitoring of blood glucose Handelsman YH, et al. Endocr Pract. 2015;21(suppl 1):1-87. ADA. Diabetes Care. 2015;38(suppl 1):S77-S79.
Jovanovic L, et al. Mt Sinai J Med. 2009;76:269-280. Castorino K, Jovanovic L. Clin Chem. 2011;57:221-230. 23 Pharmacokinetics of Insulins Safe for Use During Pregnancy 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 options Handelsman YH, et al. Endocr Pract. 2015;21(suppl 1):1-87. ADA. Diabetes Care. 2015;38(suppl 1):S77-S79. 24 Initiation of Insulin in GDM Initiate insulin when medical nutrition therapy fails to maintain glucose below the following thresholds Glucose level Fasting 105 mg/dL 1-h postprandial 155 mg/dL
2-h postprandial 130 mg/dL GDM, gestational diabetes mellitus. ADA. Diabetes Care. 2004;27(suppl 1):SS88-S90. 25 Insulin Dosing Guidelines During Pregnancy and Postpartum Weeks gestation Insulin TDD* 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]) *Use 50% of TDD for basal insulin and 50% for premeal rapid-acting insulin boluses
Decrease nighttime basal insulin by 50% in lactating women (to prevent severe hypoglycemia) Patients with T1D 10-14 weeks gestation: period of increased insulin sensitivity; insulin dosage may need to be reduced accordingly 14-35 weeks gestation: insulin requirements typically increase steadily >35 weeks gestation: insulin requirements may level off or even decline Patients with obesity may require higher insulin dosages than those without obesity TDD, total daily dose. Castorino K, Jovanovic L. Clin Chem. 2011;57:221-230. Kitzmiller JL, et al. Diabetes Care. 2008;31:1060-1079. 26 Continuous Subcutaneous Insulin Infusion During Pregnancy Benefits Mimics physiologic insulin secretion CSII devices use aspart or lispro
Safe and effective for management of GDM, T1D, or T2D No significant difference in glycemic control for pregnancy outcomes with CSII versus MDI therapy Can help address daytime or nocturnal hypoglycemia or a prominent dawn phenomenon Limitations Complexity Requires counseling and training Cost Potential for Insulin pump failure User error Infusion site problems CSII, continuous subcutaneous insulin infusion ; GDM, gestational diabetes mellitus; MDI, multiple daily injections; T1D, type 1 diabetes; T2D, type 2 diabetes. Handelsman YH, et al. Endocr Pract. 2015;21(suppl 1):1-87. Castorino K et al. Curr Diab Rep, 2012;12:53-59. Hod M. Jovanovic L. Int J Clin Pract, 2010;64:47-52. Kitzmiller JL, et al. Diabetes Care. 2008;31:1060-1079. Castorino K, Jovanovic L. Clin Chem. 2011;57:221-230. 27 Hypoglycemia in Pregnant Women With Diabetes Pathophysiology May be related
to fetal absorption of glucose from the maternal bloodstream via the placenta, particularly during periods of maternal fasting Risk Factors Causes of Iatrogenic Hypoglycemia Clinical Consequences Management History of severe hypoglycemia before pregnancy Administration of too much insulin or other antihyperglycemic medication Minor: anxiety, confusion, dizziness, headache, hunger,
nausea, palpitations, sweating, tremors, warmth, weakness Patient education on prevention and risks (especially during early pregnancy) Impaired hypoglycemia awareness Longer duration of diabetes Skipping a meal Major: coma, traffic accidents, death A1C 6.5% at first pregnancy visit High daily insulin dosage Exercising more than usual Severe hypoglycemia: maternal seizures or hypoxia
Mathiesen ER, et al. Endocrinol Metab Clin N Am. 2011;40:727-738. Inturrisi M, et al. Endocrinol Metab Clin N Am. 2011;40:703-726. Jovanovic L, et al. Mt Sinai J Med. 2009;76:269-280. Kitzmiller JL, et al. Diabetes Care. 2008;31:10601079. Hod M. Jovanovic L. Int J Clin Pract. 2010;64:47-52. Frequent SMBG Regular meal timing Accurate medication administration Exercise management 28 Treatment of Hypoglycemia Hypoglycemia symptoms (BG <70 mg/dL) Patient conscious and alert Consume glucose-containing foods (fruit juice, soft drink, crackers, milk, glucose tablets); avoid foods also containing fat Repeat glucose intake if SMBG result remains low after 15 minutes Consume meal or snack after SMBG has returned to normal to avoid recurrence Patient severely confused or unconscious (requires help) Glucagon injection, delivered by another person Patient should be taken to hospital for evaluation and
treatment after any severe episode BG, blood glucose; SMBG, self-monitoring of blood glucose. Handelsman YH, et al. Endocr Pract. 2015;21(suppl 1):1-87. 29 Physical Activity During Pregnancy Unless contraindicated, physical activity should be included in a pregnant womans daily regimen Regular moderate-intensity physical activity can help to reduce glucose levels in patients with GDM, T1D, T2D Walking Cardiovascular training with weight-bearing, limited to the upper body to avoid mechanical stress on the abdominal region Monitor for hypoglycemia GDM, gestational diabetes mellitus; T1D, type 1 diabetes; T2D, type 2 diabetes. Castorino K, Jovanovic L. Clin Chem. 2011;57:221-230. ADA. Diabetes Care. 2004;27(suppl 1):S88-S90. Jovanovic L, et al. Mt Sinai J Med. 2009;76:269-280. 30 Weight Management in Pregnant Women With Diabetes Healthy weight gain targets based on prepregnancy BMI Minimal weight gain for patients with BMI >30 kg/m2 Independent of maternal glucose levels, higher
maternal BMI associated with increased risk of: Caesarean delivery Infant birth weight >90th percentile Cord-blood serum C-peptide >90th percentile Achieve weight objectives by maintaining a balanced diet and exercising regularly BMI, body mass index. Castorino K, Jovanovic L. Clin Chem. 2011;57:221-230. Metzger BE, et al. BJOG 2010;117:575-584. 31 Labor and Delivery for Women With Diabetes Increased risk of transient neonatal hypoglycemia during the 4-6 hours prior to delivery Monitor blood glucose levels closely during labor to determine patients insulin requirements Most women with GDM will not require insulin once labor begins Endocrinologist or diabetes specialist should manage glycemia in women with T1D during labor and delivery GDM, gestational diabetes mellitus; T1D, type 1 diabetes. Castorino K, Jovanovic L. Clin Chem. 2011;57:221-230. 32 Psychological Support During Pregnancy in Women With Diabetes Individualized psychosocial interventions are likely to help improve both pregnancy outcomes and patient quality of life
Mental health professionals with expertise in diabetes should be included in 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 Snoek SJ, et al. Psychology in Diabetes Care, 2nd Ed. West Sussex, England: John Wiley & Sons Inc., 2005:54. Jovanovic L, et al. Mt Sinai J Med. 2009;76:269-280. 33 Diabetes in Pregnancy: Postpartum and Lactation Metformin and glyburide are secreted into breast milk and are therefore contraindicated during lactation Breastfeeding plus insulin therapy may lead to severe hypoglycemia Women with T1D at greatest risk Preventive measures Reduce basal insulin dosage Carbohydrate intake prior to breastfeeding Bovine-based infant formulas are linked to increased risk of T1D Avoid in offspring of women with diabetes or at risk for diabetes (eg, history of gestational diabetes, family history of diabetes) Soy-based products are a potential substitute Castorino K, Jovanovic L. Clin Chem. 2011;57:221-230. 34
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