Type 2 diabetes in pregnancy

김 성 훈

관동의대 제일병원 내과

Contents

• Case

• Risks of diabetes in pregnancy

• Risks of pregnancy for the mother with diabetes

• Risk factors for poor outcome in T2DM

• Prepregnancy care

• Management of hyperglycemia in pregnancy

증 례

• 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 임신에서 prepregnancy care 받지 않았음

• 신장 161 cm, 체중 79 kg, BMI 30.5 kg/m2

• 망막검사: mild NPDR

Classification of diabetes in pregnancy

• Type 1 diabetes (β-cell destruction)- Autoimmune

- idiopathic

• Type 2 diabetes (insulin resistance with insulin secretory defect)

• Other specific types (e.g. genetic defects of β-cell function)

• Gestational diabetes

Issues of concern

• Epidemics of obesity and T2DM -> increase in No of women with T2DM

• Frequently undiagnosed T2DM before pregnancy

• Lack of preconception care

• Increase in Cx of pregnancy due to the coexistence of obesity and T2DM

Risks of diabetes in pregnancy (I)

• Fetal macrosomia

• Birth trauma (to mother and baby)

• Induction of labor or cesarean section

Accelerated fetal growth

Risks of diabetes in pregnancy (II)

• Miscarriage

• Congenital malformation

• Stillbirth

Glucose control and risk of malformation

Guerin A. Diabetes Care 30:1920, 2007

Risks of diabetes in pregnancy (III)

• Transient neonatal morbidity- hypoglycemia, hypocalcemia, hypomagnesemia, hyperbilirubinemia, erythremia, hypertrophic cardiomyopathy, respiratory distress syndrome

• Neonatal death

• Obesity and/or diabetes developing later in the baby’s life

Maternal complications in diabetic pregnancy

• Hypoglycemia, ketoacidosis

• Pregnancy induced hypertension

• Pyelonephritis, other infections

• Polyhydramnios

• Preterm labor

• Worsening of chronic complications-retinopathy, nephropahty, neuropathy, cardiac disease

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

Cardiovascular disease

– Untreated CAD is associated with a high mortality rate during pregnancy

– Successful pregnancies have been undertaken after coronary revascularization in women with diabetes

– Exercise tolerance should be normal to maximize the probability that the patient will tolerate the increased cardiovascular demands of gestation

Potential contraindications to pregnancy

• Ischemic heart disease

• Active proliferative retinopathy, untreated

• Renal insufficiency: Ccr <50 ml/min or serum Cr >2 mg/dl or heavy proteinuria (> 2g/24 h) or hypertension (BP >130/80 mmHg despite treatment)

• Severe gastroenteropathy:nausea/vomiting, diarrhea

Remaining Problems

• A high prevalence of congenital anomalies and spontaneous abortions in infant of diabetic mothers (IDMs)

• Care of the woman with severe complications of diabetes

• Care of the ―difficult patient‖ who often presents late for antenatal care and/or nonadherent

Comparison of pregnancy outcomes in T1 and T2DM

J clin Endocrinol Metab 94:4284-91, 2009

Risk factors for poor outcome in T2DM

• Obesity - congenital malformations: NTDs (esp. spinal bifida), omphalocele, and heart defects- perinatal mortality- delivery by cesarean section- macrosomia- hypertensive disorders

• Ethnicity: Asian > Caucasian

• Poor pregnancy preparation

Paradigm shift

• Detection/diagnosis of diabetes in early pregnacy

• To consider recommendations for preconception screening to identify patients with abnormal glucose tolerance before conception

Women at very high risk for DM

1) prior history of GDM or delivery of LGA infant

2) Strong family history of T2DM

3) Diagnosis of PCOS

4) severe obesity (or BMI ≥ 30)

ADA: Standards of Medical Care in Diabetes—2011. Diabetes Care 34:S11-S61, 2011

Screen for undiagnosed T2DM at the first prenatal visit in those with risk factors, using standard diagnostic criteria (B)

임신성 당뇨병의 진단기준

당뇨병 진료지침 2011, 대한당뇨병학회

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 counselling.

• Congenital malformations.

• Perinatal complications.

• Assessment of diabetic complications.

• Review smoking, alcohol, medications, folic acid.

Laboratory and special exam of pregnant women with preexisting diabetes

Management of hyperglycemia in pregnancy

Glycemic control and perinatal outcome (I)

• Before pregnancy, in order to prevent excess spontaneous abortions and major congenital malformations, target A1C is as close to normal as possible without significant hypoglycemia. (B)

• Ensure effective contraception until stable and acceptable glycemia is achieved. (E)

• Excellent glycemic control in the first trimester continued throughout pregnancy is associated with the lowest frequency of maternal, fetal, and neonatal complications. (B)

Kitzmiller JL et al:Diabetes Care 2008;31:1060-1079

Glycemic control and perinatal outcome (II)

• Throughout 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. (B)

• Higher glucose targets may be used in patients with hypoglycemia unawareness or the inability to cope with intensified management. (E)

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 of the patient

• 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

Gynecol Endocrinol. 2010 Dec 29. [Epub ahead of print]

Exercise/Physical activity

• Educate women with diabetes as to benefits of appropriate daily physcialactivity (reduce blood glucose, weight gain and insulin requirements)

• Encourage regular exercise, at least 30 min/day

Insulin therapy

• Intensive regimen of multiple injections in a basal-bolus fashion (MDI) or an insulin pump (CSII)

Insulin profiles as used in pregnancy

Insulin profiles as used in pregnancy

Insulin Analogues in DM Pregnancy

• Rapidly acting analogues (aspart and lispro): safe

• Basal analogues not proven safe, but datemir safe in

recent trial.

We still used NPH insulin

• But during organogenesis, the risk to the fetus from

hyperglycemia is greater than any theoretical risk from

analogue insulin. Thus ? Continue analogue till 8-10 wks.

Summary and Conclusions

1. Preconception detection and management of T2DM is a critical public health issue: universal preconception screening for diabetes, with a minimun of a fasting glucose, adding an OGTT in high risk individuals

2. Women with type 2 diabetes, who are reproductive age are given preconception counselling 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