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임신과 당뇨병
김 성 훈
단국의대 제일병원 내과
Contents
• Epidemiology of diabetes in pregnancy
• Hyperglycemia and adverse outcome of
pregnancy
• Preconception counseling and
prepregnancy care
• Management of hyperglycemia in
pregnancy
• Diagnosis and management of GDM
Classification of diabetes in pregnancy
• Type 1 diabetes (results from β-cell destruction, usually
leading to absolute insulin deficiency)
• Type 2 diabetes (results from a progressive insulin
secretory defect on the background of insulin resistance)
• Other specific types of diabetes due to other causes, e.g.,
genetic defects in β-cell function, genetic defects in
insulin action, diseases of the exocrine pancreas (such as
cystic fibrosis), and drug- or chemical-induced (such as in
the treatment of HIV/AIDS or after organ
transplantation)
• Gestational diabetes mellitus (GDM) (diabetes diagnosed
during pregnancy that is not clearly overt diabetes)
한국모자보건학회지 14: 170-80, 2010
임신중 당뇨병 임부의 유병률 및 의료이용 추이
증 례 1
• 37세, 임신 9주 (gravida 3, para 2)
• 둘째 아이: 4세, 출생 체중(4500 g)
Hx of neonatal jaundice and hypoglycemia
• Random glucose; 325 mg/dl, A1C: 8.9%
• 지난 임신때 당뇨 진단 받지 않았고, 이번 임
신에서 prepregnancy care 받지 않았음
• 신장 161 cm, 체중 79 kg, BMI 30.5 kg/m2
• 망막검사: mild NPDR
Issues
• Epidemics of obesity and T2DM ->
women with T2DM become pregnant ↑
• Frequently undiagnosed T2DM before
pregnancy
• Lack of preconception care
• ↑Cx of pregnancy due to the
coexistence of obesity and T2DM
Diabetes in pregnancy and risk of
complications
• Pre-existing diabetes in pregnancy
is associated with high rates
of complications:
– Fetal/neonatal
• Congenital malformations
• Perinatal mortality
• Excess fetal growth
• Traumatic delivery
• Neonatal hypoglycaemia
• Hyperbilirubinaemia
• Diabetic fetopathy
– Maternal
• Pregnancy-induced hypertension/
pre-eclampsia
• Polyhydramnios
• Operative delivery
Dunne et al. Diabetes Care 2009;32:1205–6
Diabetes in pregnancy and risk of
complications
Outcome Pregnant women
with type 1 or
type 2 diabetes
National data
(background
population)
Rate ratio
Pre-term delivery 37% 7.3% 5
Birth weight ≥90th
percentile
52% 10% 5.2
Shoulder dystocia 7.9% 3% 2.6
Erb’s palsy 4.5/1000 0.42/1000 11
Neonatal unit
admission
56% 10% 5.6
Term admission for
special care
33% 10% 3.3
Confidential Enquiry into Maternal and Child Health (CEMACH): Pregnancy in Women with Type 1
and Type 2 Diabetes in 2002–03, England, Wales and Northern Ireland. London: CEMACH; 2005
Glucose control and risk of
malformation
Guerin A. Diabetes Care 30:1920, 2007
Glucose control and risk of
malformation
Guerin A. Diabetes Care 30:1920, 2007
For every 1%
decrease in A1c,
there is
approximately 50%
relative risk
reduction for a
congenital anomaly
Risks of pregnancy for the
mother with diabetes
• Pregnancy may affect pre-existing
micro- and macrovascular disease but
does not usually have any long-term
detrimental effect on either
retinopathy or nephropathy
• Risk of women with established
cardiovascular disease
Diabetic Retinopathy
– Diabetic retinopathy may accelerate during pregnancy
– Risk can be reduced by
• Gradual attainment of good metabolic control before
conception
• Preconceptual laser photocoagulation
– Baseline dilated comprehensive eye examination and
follow-up
; necessary before conception and during pregnancy
– Pre-existing diabetes should be counseled on the risk of
development and progression of diabetic retinopathy
Kitzmiller JL et al:Diabetes Care 2008;31:1060-1079
Diabetic nephropathy
The Pre-Preganacy Clinic
• Pregnancy planning/Contraceptive advice
• Optimize control and explain glycemic goals during pregnancy.
• Switch Type 2 diabetics to insulin. Review educational needs.
• Genetic counseling.
• Congenital malformations.
• Perinatal complications.
• Assessment of diabetic complications.
• Review smoking, alcohol, medications, folic acid.
Laboratory and special exam of pregnant women with preexisting diabetes
Kitzmiller JL et al:Diabetes Care 2008;31:1060-1079
Management of hyperglycemia in pregnancy
Optimal glycemic goals
• premeal, bedtime, and overnight glucose: 60–99 mg/dl
• peak postprandial glucose: 100–129 mg/dl
• mean daily glucose: <110 mg/dl
• A1C <6.0 %
Kitzmiller JL et al:Diabetes Care 2008;31:1060-1079
Recommended targets for capillary
glucose during pregnancy
Source Fasting 1 h Peak 2 h Premeal
ADA GDM 95 140 - 120 -
ADA preexisting 60-99 - 100-129 - 60-99
IDF 99 - 144 - -
NICE 95 140 - 115 -
ADIPS 99 144 126 126 -
Mathiesen 72-110 140 72-144 - 72-110
Assessment of metabolic control
• SMBG: daily and fingerstick
• Postprandial capillary glucose 1hr after
beginning the meal: postmeal peak glucose
• CGM: T1D, esp, hypoglycemia unawareness
• Urine ketone: ill or persistent hyperglycemia
(>200 mg/dl)
• A1C:monthly
Medical Nutrition Therapy (MNT)
• Individualized MNT
• Basic plan: dietary recommendations for all
pregnant women, adjusted to the individual needs
• CHO and caloric contents: modified based on the
woman’s height, weight, and degree of glucose
intolerance
• Carbohydrate-restricted diet; small frequent
meals and high-fiber and low GI foods
Goals for weight gain (1)
Prepregnancy BMI Total wt.gain (kg) Rate of wt.gain(2&3Tri.)kg/wk
Underweight (<18.5) 12.5 - 18 0.51 (0.44-0.58)
Normal weight (18.5-24.9) 11.5 - 16 0.42 (0.35-0.50)
Overweight (25-29.9) 7 - 11.5 0.28 (0.23-0.33)
Obese (≥30) 5 - 9 0.22 (0.17-0.27)
Institute of Medicine, 2009
Goals for weight gain (2)
• Less weight gain is safe and has a
beneficial effect on perinatal outcomes
in obese women: a weight gain of 0-7
pounds was associated with the least
macrosomia
Cheng YW et al. Gestational weight gain and gestational diabetes
mellitus: perinatal outcomes. Obstet Gynecol 112:1015-1022, 2008
Exercise/Physical activity
• Educate women with diabetes as to
benefits of appropriate daily physcial
activity (reduce blood glucose, weight
gain and insulin requirements)
• Encourage regular exercise, at least 30
min/day
Insulin therapy during pregnancy
• Basal–bolus insulin regimens (MDI) or CSII
are recommended for optimal glycaemic
control in pregnancy in women with pre-
existing diabetes
• Oral antidiabetic drugs in women with type 2
diabetes should be discontinued and insulin
initiated and titrated to achieve the
recommended glycemic control prior to
conception
Pharmacokinetics of human insulin and
insulin analogs
Type of insulin Onset of action Peak plasma values Duration of action
Regular human insulin 30-60 min 1-3 h 5-7 h
NPH insulin 60-90 min 8-12 h 18-24 h
Insulin lispro 15-60 min 0.5-1 h 2-4 h
Insulin aspart 10-20 min 1-3 h 3-5 h
Insulin glulisine 10-20 min 1-2 h 3-5 h
Glargine 4-5 h No peak >24 h
Detemir 4-6 h No peak 20 h
증 례 2
• 임신 28주의 32세 여성
• 임신 27주에 50g OCT:1시간 혈당이 174 mg/dL
• 100g OGTT: fasting-97 mg/dL, 1 hour-189
mg/dL, 2 hour-166mg/dL, 3 hour-140mg/dL
• 신장 164cm, 체중은 75kg (임신전 68kg)
• 혈압 110/70mmHg, 신체 검사, 소변검사나 다른
검사 소견은 정상
임신성 당뇨병의 진단기준
당뇨병 진료지침 2013, 대한당뇨병학회
Management of GDM
How to initiate insulin therapy: GDM
1. Short-acting insulin alone
1) each meals
2) only prebreakfast short-acting insulin for
isolated postbreakfast hyperglycemia
2. short –acting insulin and NPH (or insulin detemir)
3. premixed insulin
Summary of antepartum care
• Medical Nutritional therapy
• Regular exercise
• Maternal SMBG or fetal AC for
intensified Tx
• Insulin remains the mainstay of Tx
• glyburide and metformin may be
offered as an alternative
Insulin therapy during labor and delivery
• Maintain the maternal glucose level: 70-140 mg/dL
• 5% dextrose in half-normal saline at 100-125 ml/h
• Continue measuring BG every 1 or 2 hrs
• short-acting insulin in normal saline (eg, 25U/250 ml of saline
with 10ml/h iv and adjust the dosage to maintain the BG 70-140
mg/dL)
• Most women with GDM will not require insulin during labor
• After delivery, insulin requirements decreases sharply and
reduce the insulin dose to 25-40% of the pre-delivery
Management of women with prior GDM
Buchanan TA et al. Nat. Rev Endocrinol 8: 639, 2012
Summary
1. Preconception detection and management of T2DM
may become a critical public health issue
2. Women with diabetes who are reproductive age need
preconception counseling and prepregnancy care in
the 6-12 months before pregnancy
3. The key to improving outcome of pregnancy in
women with diabetes is strict glycemic control
4. Diagnosing and treating GDM can reduce perinatal
complications and postpartum follow up and
prevention of DM is important
감사합니다.

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임신과 당뇨병 - 제일병원 김성훈 교수

  • 1. 임신과 당뇨병 김 성 훈 단국의대 제일병원 내과
  • 2. Contents • Epidemiology of diabetes in pregnancy • Hyperglycemia and adverse outcome of pregnancy • Preconception counseling and prepregnancy care • Management of hyperglycemia in pregnancy • Diagnosis and management of GDM
  • 3. Classification of diabetes in pregnancy • Type 1 diabetes (results from β-cell destruction, usually leading to absolute insulin deficiency) • Type 2 diabetes (results from a progressive insulin secretory defect on the background of insulin resistance) • Other specific types of diabetes due to other causes, e.g., genetic defects in β-cell function, genetic defects in insulin action, diseases of the exocrine pancreas (such as cystic fibrosis), and drug- or chemical-induced (such as in the treatment of HIV/AIDS or after organ transplantation) • Gestational diabetes mellitus (GDM) (diabetes diagnosed during pregnancy that is not clearly overt diabetes)
  • 4. 한국모자보건학회지 14: 170-80, 2010 임신중 당뇨병 임부의 유병률 및 의료이용 추이
  • 5.
  • 6. 증 례 1 • 37세, 임신 9주 (gravida 3, para 2) • 둘째 아이: 4세, 출생 체중(4500 g) Hx of neonatal jaundice and hypoglycemia • Random glucose; 325 mg/dl, A1C: 8.9% • 지난 임신때 당뇨 진단 받지 않았고, 이번 임 신에서 prepregnancy care 받지 않았음 • 신장 161 cm, 체중 79 kg, BMI 30.5 kg/m2 • 망막검사: mild NPDR
  • 7. Issues • Epidemics of obesity and T2DM -> women with T2DM become pregnant ↑ • Frequently undiagnosed T2DM before pregnancy • Lack of preconception care • ↑Cx of pregnancy due to the coexistence of obesity and T2DM
  • 8. Diabetes in pregnancy and risk of complications • Pre-existing diabetes in pregnancy is associated with high rates of complications: – Fetal/neonatal • Congenital malformations • Perinatal mortality • Excess fetal growth • Traumatic delivery • Neonatal hypoglycaemia • Hyperbilirubinaemia • Diabetic fetopathy – Maternal • Pregnancy-induced hypertension/ pre-eclampsia • Polyhydramnios • Operative delivery Dunne et al. Diabetes Care 2009;32:1205–6
  • 9. Diabetes in pregnancy and risk of complications Outcome Pregnant women with type 1 or type 2 diabetes National data (background population) Rate ratio Pre-term delivery 37% 7.3% 5 Birth weight ≥90th percentile 52% 10% 5.2 Shoulder dystocia 7.9% 3% 2.6 Erb’s palsy 4.5/1000 0.42/1000 11 Neonatal unit admission 56% 10% 5.6 Term admission for special care 33% 10% 3.3 Confidential Enquiry into Maternal and Child Health (CEMACH): Pregnancy in Women with Type 1 and Type 2 Diabetes in 2002–03, England, Wales and Northern Ireland. London: CEMACH; 2005
  • 10. Glucose control and risk of malformation Guerin A. Diabetes Care 30:1920, 2007
  • 11. Glucose control and risk of malformation Guerin A. Diabetes Care 30:1920, 2007 For every 1% decrease in A1c, there is approximately 50% relative risk reduction for a congenital anomaly
  • 12.
  • 13. Risks of pregnancy for the mother with diabetes • Pregnancy may affect pre-existing micro- and macrovascular disease but does not usually have any long-term detrimental effect on either retinopathy or nephropathy • Risk of women with established cardiovascular disease
  • 14. Diabetic Retinopathy – Diabetic retinopathy may accelerate during pregnancy – Risk can be reduced by • Gradual attainment of good metabolic control before conception • Preconceptual laser photocoagulation – Baseline dilated comprehensive eye examination and follow-up ; necessary before conception and during pregnancy – Pre-existing diabetes should be counseled on the risk of development and progression of diabetic retinopathy
  • 15. Kitzmiller JL et al:Diabetes Care 2008;31:1060-1079 Diabetic nephropathy
  • 16. The Pre-Preganacy Clinic • Pregnancy planning/Contraceptive advice • Optimize control and explain glycemic goals during pregnancy. • Switch Type 2 diabetics to insulin. Review educational needs. • Genetic counseling. • Congenital malformations. • Perinatal complications. • Assessment of diabetic complications. • Review smoking, alcohol, medications, folic acid.
  • 17. Laboratory and special exam of pregnant women with preexisting diabetes Kitzmiller JL et al:Diabetes Care 2008;31:1060-1079
  • 19. Optimal glycemic goals • premeal, bedtime, and overnight glucose: 60–99 mg/dl • peak postprandial glucose: 100–129 mg/dl • mean daily glucose: <110 mg/dl • A1C <6.0 % Kitzmiller JL et al:Diabetes Care 2008;31:1060-1079
  • 20. Recommended targets for capillary glucose during pregnancy Source Fasting 1 h Peak 2 h Premeal ADA GDM 95 140 - 120 - ADA preexisting 60-99 - 100-129 - 60-99 IDF 99 - 144 - - NICE 95 140 - 115 - ADIPS 99 144 126 126 - Mathiesen 72-110 140 72-144 - 72-110
  • 21. Assessment of metabolic control • SMBG: daily and fingerstick • Postprandial capillary glucose 1hr after beginning the meal: postmeal peak glucose • CGM: T1D, esp, hypoglycemia unawareness • Urine ketone: ill or persistent hyperglycemia (>200 mg/dl) • A1C:monthly
  • 22. Medical Nutrition Therapy (MNT) • Individualized MNT • Basic plan: dietary recommendations for all pregnant women, adjusted to the individual needs • CHO and caloric contents: modified based on the woman’s height, weight, and degree of glucose intolerance • Carbohydrate-restricted diet; small frequent meals and high-fiber and low GI foods
  • 23. Goals for weight gain (1) Prepregnancy BMI Total wt.gain (kg) Rate of wt.gain(2&3Tri.)kg/wk Underweight (<18.5) 12.5 - 18 0.51 (0.44-0.58) Normal weight (18.5-24.9) 11.5 - 16 0.42 (0.35-0.50) Overweight (25-29.9) 7 - 11.5 0.28 (0.23-0.33) Obese (≥30) 5 - 9 0.22 (0.17-0.27) Institute of Medicine, 2009
  • 24. Goals for weight gain (2) • Less weight gain is safe and has a beneficial effect on perinatal outcomes in obese women: a weight gain of 0-7 pounds was associated with the least macrosomia Cheng YW et al. Gestational weight gain and gestational diabetes mellitus: perinatal outcomes. Obstet Gynecol 112:1015-1022, 2008
  • 25. Exercise/Physical activity • Educate women with diabetes as to benefits of appropriate daily physcial activity (reduce blood glucose, weight gain and insulin requirements) • Encourage regular exercise, at least 30 min/day
  • 26. Insulin therapy during pregnancy • Basal–bolus insulin regimens (MDI) or CSII are recommended for optimal glycaemic control in pregnancy in women with pre- existing diabetes • Oral antidiabetic drugs in women with type 2 diabetes should be discontinued and insulin initiated and titrated to achieve the recommended glycemic control prior to conception
  • 27. Pharmacokinetics of human insulin and insulin analogs Type of insulin Onset of action Peak plasma values Duration of action Regular human insulin 30-60 min 1-3 h 5-7 h NPH insulin 60-90 min 8-12 h 18-24 h Insulin lispro 15-60 min 0.5-1 h 2-4 h Insulin aspart 10-20 min 1-3 h 3-5 h Insulin glulisine 10-20 min 1-2 h 3-5 h Glargine 4-5 h No peak >24 h Detemir 4-6 h No peak 20 h
  • 28. 증 례 2 • 임신 28주의 32세 여성 • 임신 27주에 50g OCT:1시간 혈당이 174 mg/dL • 100g OGTT: fasting-97 mg/dL, 1 hour-189 mg/dL, 2 hour-166mg/dL, 3 hour-140mg/dL • 신장 164cm, 체중은 75kg (임신전 68kg) • 혈압 110/70mmHg, 신체 검사, 소변검사나 다른 검사 소견은 정상
  • 29. 임신성 당뇨병의 진단기준 당뇨병 진료지침 2013, 대한당뇨병학회
  • 30.
  • 32. How to initiate insulin therapy: GDM 1. Short-acting insulin alone 1) each meals 2) only prebreakfast short-acting insulin for isolated postbreakfast hyperglycemia 2. short –acting insulin and NPH (or insulin detemir) 3. premixed insulin
  • 33. Summary of antepartum care • Medical Nutritional therapy • Regular exercise • Maternal SMBG or fetal AC for intensified Tx • Insulin remains the mainstay of Tx • glyburide and metformin may be offered as an alternative
  • 34. Insulin therapy during labor and delivery • Maintain the maternal glucose level: 70-140 mg/dL • 5% dextrose in half-normal saline at 100-125 ml/h • Continue measuring BG every 1 or 2 hrs • short-acting insulin in normal saline (eg, 25U/250 ml of saline with 10ml/h iv and adjust the dosage to maintain the BG 70-140 mg/dL) • Most women with GDM will not require insulin during labor • After delivery, insulin requirements decreases sharply and reduce the insulin dose to 25-40% of the pre-delivery
  • 35. Management of women with prior GDM Buchanan TA et al. Nat. Rev Endocrinol 8: 639, 2012
  • 36. Summary 1. Preconception detection and management of T2DM may become a critical public health issue 2. Women with diabetes who are reproductive age need preconception counseling and prepregnancy care in the 6-12 months before pregnancy 3. The key to improving outcome of pregnancy in women with diabetes is strict glycemic control 4. Diagnosing and treating GDM can reduce perinatal complications and postpartum follow up and prevention of DM is important