Management of diabetes in pregnancy

So Young Park, M.D.

용어 정의

• 임신성 당뇨병 (gestational diabetes, GDM) :

기존에 당뇨병이 없는 상태에서 임신 기간중에 진단된 당뇨병

• 임신전 당뇨병 (preexisting diabetes, PGDM) :

임신전에 당뇨병이 진단되어 있는 경우

• 임신과 관련한 위험 - 태아의 고인슐린혈증 - 거대아 - 사산 - 양수과다증 - 임신중 고혈압 - 분만후 당뇨병의

위험성 증가

• 당뇨병 종류 - 제 1 형 당뇨병 - 제 2 형 당뇨병

• 임신과 관련한 위험 - 임신초기 ; 선천성 기형 ,

자연유산 - 임신후기 ; 고인슐린혈

증 , 거대아 , 사산 , 호흡곤란증

GDM PGDMvs.

Background

• In 1939, ‘‘benign glycosurics are more likely to give birth to larger babies than do normal women’’

• In 1952, a link between higher maternal glucose during pregnancy and neonatal hypoglycemia hypothesizing the involvement of fetal hyperinsulinemia

• In 1957, ‘‘gestational diabetes’’ by Carrington

• O’Sullivan focused on the long-term risk of diabetes developing in high risk women and using the pregnancy OGTT proposed using an upper cutoff of 2SD above the mean.

O’Sullivan criteria for diagnosing GDM with subsequently derived values

Pathophysiology of GDM

Gestational Diabetes: Caring for Yourself and Your Baby, IDC Publishing

Diagnosis of GDM

• Two step approach

- Perform screen using 50 g oral glucose load and check blood glucose at 1 hour

Diagnosis of GDM

* Two or more values meeting or exceeding the cut points are required for diagnosis.

• An observational study• 23,316 pregnant women• A 75 g OGTT with sampling at 0, 1, and 2 hours• Primary outcomes : large for gestational age (LGA), clinical neonatal hypoglycemia, cord blood C-peptide > the 90th percentile, primary cesarean section delivery rate

Frequency of primary outcomes across the glucose categories (HAPO study)

N Engl J Med 2008;358:1991-2002

International Association of Diabetes in Pregnancy Study Groups (IADPSG)

Recommendations

Diabetes Care 2010;33:676–81

Screening for and diagnosis of GDM

Diabetes Care. 2013;36 (suppl 1):S67–S74.

• Two-step approaches• screening 50g → 100g 3-hour OGTT• Based on the likelihood that a

woman would develop DM several years subsequent to pregnancy

• Evidence has accumulated ; the association of GDM with an increased risk of adverse maternal and perinatal outcomes.

• GDM diagnosis ; 5 ~ 6% of the population

• Single-step approaches• 75g 2-hour OGTT

• Based on demonstrated associations between glycemic levels and an increased risk of obstetric and perinatal morbidities.

• GDM diagnosis ; 15 ~ 20% of the population

• It is not well understood whether additional GDM women will benefit from treatment.

ACOG position IADPSG/ADA positionvs.

• The panel believes that there is not sufficient evidence to adopt a one-step approach, such as that proposed by the IADPSG.

• The panel is particularly concerned about the adoption of new criteria that would increase the prevalence of GDM, and the corresponding costs and interventions, without clear demonstration of improvements in the most clinically important health and patient-centered outcomes.

• Thus, the panel recommends that the two-step approach be continued.

Fetal outcomes related to GDM

Potential maternal complications of GDM

J Matern Fetal Neonatal Med 2010;23(3):199-203

Effects of treating GDM ; Meta-analysis of RCT

Outcome Risk Ratio (95% CI)

Fetal

Shoulder dystocia 0.42 (0.23–0.77)

Neonatal hypoglycemia 1.18 (0.92–1.52)

Macrosomia

(birthweight >4000 g)

0.50 (0.35–0.71)

Admission to the NICU 0.96 (0.67–1.37)

Maternal

Cesarean delivery 0.90 (0.79–1.01)

Preeclampsia 0.62 (0.43–0.89)

Ann Intern Med. 2013;159:123-129

Recommended targets for home-monitored glucose levels during pregnancy

Endocrinol Metab Clin N Am 2012;41:161–173

(95) (140) (120)

(99)

(100-129)(60-99)

(144)

(63-106) (140)

(99) (144) (126) (126)

(72-108) (140)

본원 70-100 100-140 90-120 90-120a

Medical management

• Self-glucose monitoring

• Diet/Exercise

• Oral agents

• Insulin

Self-glucose monitoring

• The cornerstone of diabetes management in GDM

• Glucose monitoring ≥3 times daily

- Morning fasting

- 2-hour postprandial (breakfast, lunch, and dinner)

- Before bed

Medical nutrition therapy (MNT)

• Medical nutrition therapy (MNT) and lifestyle changes can effectively manage 80% to 90% of mild GDM cases.

• MNT nutritional goals and recommendations:– Choose healthy low-carbohydrate, high-fiber sources of nutrition,

with fresh vegetables as the preferred carbohydrate sources– 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

• As pregnancy progresses, glucose intolerance typically worsens; patients may ultimately require insulin therapy.

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.

식사요법의 실제

• 3 식 + 2~4 간식

• 표준체중 계산 : (kg)=( 키 cm-100)x0.9• 총열량 (kcal)= 표준체중 x25~30kcal + 300~350kcal

• 영양소 배분 : 탄수화물 50%, 단백질 20%, 지방 25-30%

• 식품군 1 단위당 칼로리 : 곡류군 (100 칼로리 ), 어육류군 (50~100 칼로리 ), 채소군 (20 칼로리 ), 지방군 (45 칼로리 ), 우유군 (125 칼로리 ), 과일군 (50 칼로리 )

식품 교환표

Ex) 1900kcal = 곡류군 8 단위 + 어육류군 ( 저지방 2 + 중지방 4) + 채소군 7단위 + 지방군 5 단위 + 우유군 2 단위 + 과일군 2 단위

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 GDM.

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.

Oral agents for the management of GDM

• When MNT alone fails, pharmacologic therapy is indicated– AACE guidelines recommend insulin as the optimal approach

• Metformin and glyburide (sulfonylurea) are the 2 most commonly prescribed oral antihyperglycemic agents during pregnancy.

• Due to efficacy and safety concerns, the ADA does not recommend oral antihyperglycemic agents for gestational diabetes mellitus (GDM) or preexisting T2DM.

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.

Medication Crosses Placenta

FDA Classification Notes

Metformin Yes Category B Metformin and glyburide may be insufficient to maintain normoglycemia at all times, particularly during postprandial periods

Glyburide Minimal transfer

Some formulations category B, others category C

When to add insulin

• If medical nutritional therapy (MNT) fails then add insulin when glucose are:

ADA ACOG

Fasting ≥ 105 mg/dL ≥ 95 mg/dL

1-H postprandial ≥ 155 mg/dL ≥ 130-140 mg/dL

2-H postprandial ≥ 130 mg/dL ≥ 120 mg/dL

Insulin use during pregnancy

Patient Education

• Insulin administration, dietary modifications in response to self-monitoring of blood glucose (SMBG), hypoglycemia awareness and management

Basal Insulin

• Intermediate- or long-acting insulin administered by injection, or• Rapid-acting insulin administered by insulin pump

Postprandial hyperglycemia

• Recommended approach: rapid-acting insulin analogues

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.

Characteristics of various insulin preparations

Onset, h Peak, h Duration, h FDA category

Rapid-acting analogs

Lispro (Humalog®) 0.25~0.5 0.5~2.5 3~5 B

Aspart (Novorapid®) <0.25 1~3 3~5 B

Intermediate-acting

NPH, isophane 2~4 4~10 10~16 B

Long-acting analogs

Detemir (Levemir®) 2 No peak 7.6~24 B

Glargine (Lantus®) 2 No peak 11~24 C

Premixed

75% lispro protamine/25% lispro B

70% aspart protamine/30% aspart B

50% aspart protamine/50% aspart B

Management during labor

During labor :• Maternal hyperglycaemia during labour neonatal hypoglycaemia ∝ → target glycaemic control ; 72 ~ 144 mg/dl• For women with PGDM, an insulin infusion is usually required to

achieve normoglycaemia.• Women with GDM are usually able to maintain the required blood

glucose targets without requiring an intravenous insulin or with reduced insulin dose.

After delivery :• PGDM; Insulin requirements fall to pre-pregnancy levels.• GDM: Hypoglycaemic agents can be discontinued following birth.• Breastfeeding is encouraged.

Postgrad Med J 2011; 87: 417-427

Risks factors for diabetes following a gestational diabetes pregnancy

• Family origin with high prevalence of diabetes ; South Asian, black Caribbean, Middle Eastern

• Insulin treatment in pregnancy• Maternal obesity• Weight gain postpartum• Family history of diabetes

Postgrad Med J 2011; 87: 417-427

Suggested management of women with prior GDM

Nat Rev Endocrinol 2012;8:639–649

At 1–4 months postpartum (6-8 wk)

Take home messages

• Gestational diabetes mellitus (GDM) is caused by reduced pancreatic β‑cell function, which results from the full spectrum of causes of β‑cell dysfunction.

• GDM is associated with a modest increase in adverse perinatal outcomes, an increased risk of obesity in offspring and a high risk of subsequent development of DM in mothers.

• GDM is treated nutritionally; insulin or oral antidiabetic agents can be added if maternal glucose levels and/or fetal growth parameters indicate a sufficiently high risk of perinatal complications.

• Long-term management of mothers includes assessment of diabetes risk, and lifestyle and/or pharmacological approaches for women at risk of type 2 diabetes mellitus.

Thank you for your attention…