DIABETES DAN KEHAMILAN

Lab Farmakologi
FKUB
MALANG

2 BAGIAN :
1. Preexisting DM and pregnancy
2. Gestational diabetes

Diabetes in pregnancy
Pre-existing diabetes

IDDM
(Type1)

NIDDM
(Type2)

Gestational diabetes

Pre-existing diabetes

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

Preexisting DM in
Pregnancy

(2) Fetal
1. increase risk of congenital abnormalities
sacral agenesis, congenital heart disease,
neural tube defects
Hba1c level
normal
<8%
>10%

Risk
not increased
5%
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
Hypoglycemia
Infection
Ketoacidosis
Deterioration in retinopathy
Increased proteinuria+edema
Miscarriage
Polyhydramnio
Shoulder dystocia
Preeclampsia
Increased caesarean rate

Fetal:
Congenital abnormalities
Increased neonatal and perinatal
mortality
Macrosomia
Late stillbirth
Neonatal hypoglycemia
Polycythemia
jaundice

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
outcomes

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 drug
Commonly used in Polycystic Ovarian Disease
(PCOD) to treat insulin resistance and normalize
reproductive function
Not teratogeneic
Reduce first trimester miscarriage
10X reduce gestational diabetes

Glueck, Fertil Steril 2002

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

Oral hypoglycemic
agents
Sulfonylureas
1st generation drug increase risk of neonatal hypoglycemia
2nd generation drug (Glyburide) no such effect and other
morbidities .
Cat C drug
4%-20% patients failed to achieve glucose control with
maximum dose of drug
Increase risk of preeclampsia and need for phototherapy

Langer, N Eng Med J , 2000

Kremer, Am J Obst Gynaecol, 2004
Chmait, J Perinatol ,2004
Langer, Am J Obst Gynaecol, 2005

Management
Aim
Achieve maternal near normoglycemic
level to prevent adverse perinatal
outcomes

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 drug
Commonly used in Polycystic Ovarian Disease
(PCOD) to treat insulin resistance and normalize
reproductive function
Not teratogeneic
Reduce first trimester miscarriage
10X reduce gestational diabetes

Glueck, Fertil Steril 2002

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

Oral hypoglycemic
agents
Sulfonylureas
1st generation drug increase risk of neonatal
hypoglycemia
2nd generation drug (Glyburide) no such effect and other
morbidities .
Cat C drug
4%-20% patients failed to achieve glucose control with
maximum dose of drug
Increase risk of preeclampsia and need for phototherapy
Langer, N Eng Med J , 2000
Kremer, Am J Obst Gynaecol, 2004
Chmait, J Perinatol ,2004
Langer, Am J Obst Gynaecol, 2005

Insulin Analogues
1. rapid-acting insulin analogs
(lispro) Cat B
concerns about teratogenesis, antibodies formation,
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
hstix
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
retinopathy
Should counsel that good control and lower hba1c lower
the risk of congenital abnormalities and improve outcome
If necessary, proliferative retinopathy may be treated with
photocoagulation prior to conception
Contraindications 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 2428 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. polyhydramnion
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
Impaired fasting glucose

6.1-6.9

IGT
DM

<or =7
>or = 7

2 hr (mmol/L)

and
or

7.8-11
> 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 fractures
Increase in neonatal hypoglycemia (24% ),
hyperbilirubinemia, hypocalcemia, polycythemia
Children 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 womans 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 Pregnancy

Conclusion
(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 pregnancy

conclusion
(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!