diabetes and pregnancy dr wong pui yee, bonnie mbchb, mrcog fhkam(og), fhkcog subspecialist in fetal...

Diabetes and Pregnancy

Dr Wong Pui Yee, Bonnie

MBChB, MRCOGFHKAM(OG), FHKCOG

Subspecialist in Fetal Maternal Medicine

2 parts:

Preexisting DM and pregnancy

Gestational diabetes

Diabetes in pregnancy

Pre-existing diabetes Gestational diabetes

Pre-existing diabetesIDDM

(Type1)NIDDM(Type2) True GDM

Preexisting diabetes in pregnancy

Type 1 DM ( IDDM)

Type 2 DM (NIDDM)

Preexisting DM in pregnancy

Effect of pregnancy on pre-existing DM

• Increase requirement for insulin doses

• Nephropathy , autonomic neuropathy may deteriorate

• Progress in diabetic retinopathy (2X)

• Hypoglycemia

• Diabetic ketoacidosis

Preexisting DM In Pregnancy

Effect of preexisting DM on pregnancy

(1) Maternal

1. increase risk of miscarriage

2. increase risk of preclampsia

3. increase risk of infection eg vaginal candidiasis, UTI, endometrial or wound infection

4. increase LSCS rate

Preexisting DM in Pregnancy

(2) Fetal

1. increase risk of congenital abnormalities

sacral agenesis, congenital heart disease,

neural tube defects Hba1c level Risk

normal not increased

<8% 5%

>10% 25 %

Preexisting DM in Pregnancy

2. Perinatal mortality (excluding congenital abnormality ) 2 fold increased

3. Increase risk of sudden unexplained intrauterine fetal death.

Complications of pregnancy in pre-existing DM

Maternal:Increase insulin requirment’HypoglycemiaInfectionKetoacidosisDeterioration in retinopathy’Increased proteinuria+edemaMiscarriagePolyhydramnioShoulder dystociaPreeclampsiaIncreased caesarean rate

Fetal: Congenital abnormalitiesIncreased neonatal and perinatal morta

lityMacrosomiaLate stillbirthNeonatal hypoglycemiaPolycythemiajaundice

Maternal hyperglycemia

|

Fetal hyperglycemia

|

Fetal pancreatic beta-cell hyperplasia

|

Fetal hyperinsulinaemia

|

Macrosomia,organomegaly, polycythaemia, hypoglycemia, RDS

Management

Aim

Achieve maternal near normoglycemic level to prevent adverse perinatal outc

omes

Diet

Low-carbohydrate diet , high fibre with caloric restriction

Frequent small snacks may be needed between meals

Avoid starvation

Insulin

3 pre-meal short acting insulin (actrapid) +/- intermediate-acting insulin (protophane) as it allows maximum flexibility

Target blood glucose:

fasting < 5mmol/L

2 hr <7 mmol/L

Oral Hypoglycemic agents

Implicated as teratogeneic in animal studies esp first generation sulfonyureas

In humans, scattered case reports of congenital abnormality

Risk of congenital abnormality related to maternal glycemic control rather than mode of the anti-DM agents

Oral hypoglycemic agents

For Type 2 DM patients,

to stop oral hypoglycemic agents and change to insulin

Reassure that the risk of congenital abnormality due to drug is small

Oral hypoglycemic agents

Biguanides ( metformin)Cat B drugCommonly used in Polycystic Ovarian Disease (PCOD) to treat insulin resistance and normalize reproductive functionNot teratogeneicReduce first trimester miscarriage10X reduce gestational diabetes

Glueck, Fertil Steril 2002Reece, Curr Opin Endocrinol Diabetes, 2006Hague, BMJ, 2003Glueck, Human Reprod, 2004

Oral hypoglycemic agents

Sulfonylureas1st generation drug increase risk of neonatal hypoglycemia2nd generation drug (Glyburide) no such effect and other morbidities . Cat C drug4%-20% patients failed to achieve glucose control with maximum dose of drugIncrease risk of preeclampsia and need for phototherapy

Langer, N Eng Med J , 2000Kremer, Am J Obst Gynaecol, 2004Chmait, J Perinatol ,2004Langer, Am J Obst Gynaecol, 2005

Insulin Analogues

1. rapid-acting insulin analogs

(lispro) Cat B concerns about teratogenesis, antibodies formatio

n, growth-promoting properties

majority of evidence showed that it does not cross placenta, and has no adverse maternal or fetal effects

Insulin Analogues

2. Long acting analogs

glargine

Cat C drug

Not well studied systemically

Monitoring

Regular home glucose monitoring with h’stix

Insulin may be need to be adjusted as gestation advances

Hba1c monitoring

Fetal monitoring with USG

Refer ophthamologist

Delivery

Timing and mode of delivery individualised

Intrapartum insulin infusion with glucose monitoring

no contraindication for Breast feeding either with insulin or oral hypoglycemic agents

Pre-conception Counselling

Allows for optimisation of diabetic control prior to conception, and assessment of the presence of complications like hypertension, nephropathy, and retinopathyShould counsel that good control and lower hba1c lower the risk of congenital abnormalities and improve outcomeIf necessary, proliferative retinopathy may be treated with photocoagulation prior to conceptionContraindications to pregnancy only :ischemic heart dx, untreated proliferative retinopathy, severe renal impairment(creatinine>250 mmol/L)

Gestational diabetes

Definition

Carbohydate intolerance of variable severity first recognised during the present pregnancy.

This includes women with preexisting but previously unrecognised diabetes

Gestational diabetes

No consensus for 4 decades!

Gestational diabetes

Should all pregnant women be screened or only those with risk factors?Is it safe to screen all?Which screening test and which diagnostic test are the most reliable?Which cut-off values should we use?What are the risk for mothers and babies and can treatment improve outcome?What are the connection between gestational diabetes and type 2 DM?Is it physiological or pathological ?

Gestational diabetes

Screening and diagnosis

In general, the test is performed btn 24-28 wk because at this point in gestation the diabetogenic effect of pregnancy is manifest and there is sufficient time remaining in pregnancy for therapy to exert its effect

Gestational diabetes

Screening and diagnosis In general, risk factor includes: 1. age>25y 2. BMI > 25 3. previous GDM 4. Family hx of DM in 1st degree relative 5. previous macrosomic baby (<4 kg) 6. polyhydramnio 7. large for date baby in current pregnancy 8. previous unexplained stillbirth

Gestational diabetes

Screening

Fasting / random glucose/ glucose challenge test(50gm)

Diagnosis

Glucose challenge test

(75gm/100gm ?)

Gestational diabetes

Diagnosis

WHO criteria 1998,

75 gm glucose fasting 2 hr (mmol/L)

Impaired fasting glucose 6.1-6.9

IGT <or =7 and 7.8-11

DM >or = 7 or > or=11.1

Gestational diabetes

Incidence

2-9%

more common in Asian and Indian women

In developed countries, increasing trend because of epidemic of obesity

Gestational diabetes

Clinical significance of GDM

1. High incidence of macrosomia, and adverse pregnancy outcomes,

2. A significant proportion(30%) identified as GDM in fact have DM before pregnancy

Gestational diabetes

Women with glucose intolerance just above normal range are at low risk for pregnancy complications, those with more severe glucose intolerance approaching the criteria of diabetes are at risk of neonatal complications

Fetal complications

Macrosomia (>4 kg) risk is 16-29% as compared to 10% in control

Increase in caesarean delivery, intrumental deliveries ( forceps/vacuum), birth trauma, such as brachial plexus injuries , clavicular fracturesIncrease in neonatal hypoglycemia (24% ), hyperbilirubinemia, hypocalcemia, polycythemiaChildren are at risk of type 2 DM and obesity in life

Maternal complications

Increase risk of hypertensive disorders

Increase risk of caesarean and intrumental deliveries

Increased Risk (40-60%) of developing type 2 DM within10-15 yr.

Gestational diabetes

Does treatment improves outcomes?Conflicting results 1. Cochrane datebase systemic review 2005 (3 studies only) no difference in outcomes except neonatal hypoglycemia

2. Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS study) 2005 ( 490/510 subjects)

treatment of diabetes reduces serious perinatal morbility and may improve the woman’s health-related quality of life

Gestational diabetes

Large randomized study on going

HAPO trial in USA

(Hyperglycemia and Adverse Pregnancy Outcome study)

Gestational diabetes

Management

Management similar as preexisting DM

Need for glucose monitoring

Start with Diet control

Commence insulin for poor control

Delivery plan individualised

Gestational diabetes

In view of risk of developing type 2 DM

the woman should be screened annually for DM on yearly basis.

Diabetes and PregnancyConclusion

(1) Preexisting DM in pregnancy

• Good glucose control is important for decreasing morbidities

• Insulin is still the gold standard of tx in pregnancy

• Increasing evidence for clincial effectiveness for treatment with oral hypoglycemic agents

Diabetes and pregnancyconclusion

(2) Gestational diabetes

no consensus

The morbidities increases as glucose level approaching the diagnosis as DM

Possible that treatment improves outcomes

Overlap with preexisting DM, esp type2

Long term implication for health of the mother and baby

Thank you very much!