Gestational Diabetes is a highly prevalent condition, which has a great impact on maternal and fetal Health. It a condition triggered by metabolic adaption, which occurs during the second half of pregnancy. The aim of this review to discuss the advances in management of GDM, as well as their implications in the field, the issue of hyperglycemia in early pregnancy. Pre-eclampsia is a multisystemic disease characterized by the development of hypertension after 20 weeks of gestation, with the presence of proteinuria or, in its absence, of signs or symptoms indicative of target organ injury.
2. Defined as carbohydrate intolerance of variable
severity with onset or first recognition during
pregnancy.
The entity usually presents late in the second or
during the third trimester.
Gestational diabetes affects 3–9% of
pregnancies, affecting 1% of those under the age
of 20 and 13% of those over the age of 44.
GESTATIONAL DIABETES
INTRODUCTION
3. This diagnosis is given when a woman, who has
never had diabetes before, gets diabetes or has high
blood sugar, when she is pregnant.
Its medical name is gestational diabetes mellitus or
GDM.
It is one of the most common health problems for
pregnant women.
The word “gestational” actually refers to “during
pregnancy.”
INTRODUCTION
4. Body normally makes a hormone called insulin that
moves gluocse out of the blood and into the cells of
the body.
Women with gestational diabetes develop resistance to
insulin and cannot move glucose into the cells. This
causes the blood sugar level to remain too high.
GESTATIONAL DIABETES
5. Risk Factors
Strong familial history of diabetes
Body mass index >30 kg/m2
Previous gestational diabetes.
Have given birth to large infants (4 kg or more)
Previous polyhydromnios.
Previous unexplained fetal losses
Over the age of 30
Ethnic group (East Asian, pacific island ancestry
6. Polyhydramnios is a medical condition describing an excess
of amniotic fluid in the amniotic sac. It is seen in about 1% of
pregnancies.
There are two clinical varieties of polyhydramnios: chronic
polyhydramnios where excess amniotic fluid accumulates
gradually, and acute polyhydramnios where excess amniotic fluid
collects rapidly.
EFFECTS OF DIABETES ON PREGNANCY
8. Insulin resistance is a normal phenomenon emerging in the
second trimester of pregnancy, which in cases of GDM
progresses thereafter to levels seen in a non-pregnant person
with type 2 diabetes.
The primary function of β-cells is to store and secrete
insulin in response to glucose load. When β-cells lose the
ability to adequately sense blood glucose concentration, or
to release sufficient insulin in response, this is classified as
β-cell dysfunction.
GESTATIONAL DIABETES
9. For diagnosis of GDM, there is variation of concept. American
Diabetic Association (ADA) prefers to do screening and diagnostic
tests.
The most utilized screening test is 50-g non-fasting one-hour glucose
challenge test. Screening cutoffs are 130 mg/dL (7.20mmol/ L; 90
percent sensitivity) or 140 mg/ dL (7.75mmol/ L; 80 percent
sensitivity). The most recent ADA and American College of Obstetrics
& Gynecology (ACOG) guidelines recommend the same cutoff values
. Random or fasting glucose measurement is not recommended for
screening because of poor specificity.
In general, screening and diagnostic tests are performed between 24
and 28 weeks, because at this point in gestation the diabetogenic effect
of pregnancy is manifested. In contrast, women at high risk of
gestational diabetes should be screened at their first antepartum visit.
DIAGNOSIS
11. DIAGNOSTIC TEST
The oral glucose tolerance test (OGTT) was the gold standard
for making the diagnosis of type 2 diabetes. It is still commonly
used during pregnancy for diagnosing gestational diabetes. With
an oral glucose tolerance test, the person fasts overnight (at least
8 hours, but not more than 16 hours). The next morning, the
fasting plasma glucose is tested. After this test, the person
receives a dose of oral glucose (the dose depends upon the
length of the test). There are several methods employed by
obstetricians to do this test, but the one described here is
standard. Usually, the glucose is in a sweet-tasting liquid that the
person drinks. Blood samples are taken up to four times at
different time points after consumption of the sugar to measure
the blood glucose.
GESTATIONAL DIABETES
12. Oral glucose tolerance test (OGTT)
Procedure :
Carbohydrate intake of at least 150 g/day 3 days prior to
test, then fast for 10 to 16 hours.
100 grams or 75 grams of anhydrous dextrose powder
• Drink within 5 minutes (first swallow is time zero)
• Terminate test should nausea and vomiting occur
Abstain from tobacco, coffee, tea, food and alcohol during
test
Sit upright and quietly during the test , Slow walking is
permitted but avoid vigorous exercise
Collect samples at 0, 1 ,2 and 3 hours
GESTATIONAL DIABETES
13. Fasting blood glucose level ≥95 mg/dl (5.33 mmol/L)
1 hour blood glucose level ≥180 mg/dl (10 mmol/L)
2 hour blood glucose level ≥155 mg/dl (8.6 mmol/L)
3 hour blood glucose level ≥140 mg/dl (7.8 mmol/L)
NOTE:
At present, the most commonly used internationally used test
is the 2-hour 75 g OGTT. This is the test recommended by
WHO and it is used in Europe.
GESTATIONAL DIABETES
Result:
14. Patient consume at least 150g carbohydrate for 3 days prior
to test
Patient should rest, no smoking, no drugs, no signs and
symptoms of infection
Fasting for 12hours is recommended and maternal
venous blood is drawn to measure the fasting blood
glucose level
A 75g glucose in 300ml drink is given to the patient and
blood is drawn at intervals to measure glucose levels.
Only a fasting and 120min sample are needed.
75g Oral Glucose Tolerance test- Modified
Oral Glucose Tolerance (MGTT)
15. Catergory Normal IGT Diabetes
Mellitus
Fasting <5.6 5.6-7.8 >7.8
2hrs <7.8 7.8-11.1 >11.1
WHO Criteria for oral glucose
tolerance test (OGTT)
16. RISKS FOR MOTHER
• Preterm labor
• C-section
• Developing High Blood pressure
• Developing Type II Diabetes later in life
POTENTIAL RISKS OF UNTREATED GESTATIONAL
DIABETES
17. RISKS FOR CHILD
• Stillbirth
• Birth Defects
• Respiratory Distress syndrome
• Becoming obese as children or adults
• Developing Diabetes
POTENTIAL RISKS OF UNTREATED GESTATIONAL
DIABETES
18. MACROSOMIA
In this condition, the baby’s body is larger than normal. Large-bodied babies
may be injured during natural delivery through the vagina, so the baby may
need to be delivered through cesarean section.
HYPOGLYCEMIA
In this condition, the baby’s blood glucose is too low. Breastfeeding may need
to be started right away to get more glucose into the baby’s system. If
breastfeeding is not possible, then the baby may need to get glucose put
directly into the blood through a thin, plastic tube in his or her arm.
JAUNDICE
In this condition ,the baby’s skin turns yellowish. The white parts of the eye
may also change color slightly. If treated, this is not a serious problem.
RESPIRATORY DISTRESS SYNDROME (RDS)
In this condition, the baby has trouble breathing. The baby may need oxygen
or other help breathing if he or she has this condition.
GDM Associated Conditions
19. MACROSOMIA
Figure 2. (Left) A macrosomic baby born to a mother with diabetes.
(Right) A normal baby born to a mother without diabetes.
GDM Associated Conditions
20. LOW CALCIUM AND MAGNESIUM LEVELS IN BABY’S
BLOOD
In this condition, spasms in the hands and feet, or twitching and
cramping of muscles can occur. The condition can be treated through
supplementation with magnesium and calcium supplements.
NOTE: Keep in mind that just because you have GDM it does not
mean that these problems will occur.
Gestational diabetes usually does not cause birth defects or
deformities.
GDM Associated Conditions
21. The fact that you have gestational diabetes will not cause
diabetes in your baby. However, your child will be at a higher
risk for developing type 2 diabetes in adulthood and may get it
at a younger age (younger than 30).
Macrosomic or large-bodied babies are at higher risk for
childhood and adult obesity.
CONTINUE…
22. MAGNETIC RESONANCE IMAGE OF PREGNANCY
COMPLICATED BY DIABETES
NORMOGLYCMIA HYPERGLYCMIA
GESTATIONAL DIABETES
24. Recent data provide strong evidence that proper treatment of GDM
reduces adverse maternal and perinatal outcomes. The Australian
Carbohydrate Intolerance Study in Pregnant Women randomized
women to receive routine care or treatment for gestational diabetes
. Primary fetal outcomes included death, shoulder dystocia, bone
fracture, and macrosomia.
. Primary maternal outcomes were induction of labor and caesarean
delivery. Infants of women in the treatment group had significantly
fewer perinatal complications.
25. A. Diet
First-line therapy for women with gestational diabetes is dietary
modification, often referred to as medical nutritional therapy
(MNT). This is best done in consultation with an experienced
nutritionist, and should take cultural preferences into account. The
ADA also recommends nutritional counseling, if possible by a
registered dietitian, with individualization of the nutrition plan
based on height and weight. For normal-weight women (BMI: 20-
24 kg/m2) 30 kcal/kg.
MANAGEMENT
26. In the management of Type 2 DM in non- pregnant condition, physical
exercise is advocated. Very few studies or reports on the effects of physical
activity for the prevention or treatment of gestational diabetes are available
at present. Dempsey et al.; in a prospective study and in a case-control
study showed that lean as well as overweight women who were physically
active before and/or during pregnancy experienced statistically significant
reduced risks of GDM (48% risk reduction). In 2006, Zhang et al. found
that vigorous physical activity before pregnancy and continuation of
activity during early pregnancy may reduce the risk of developing abnormal
glucose tolerance and GDM.
B. Exercise
27. In non-pregnant individuals, pre-prandial(done before a meal) blood
glucose is generally monitored.
A randomized trial comparing pre-prandial to 1-h postprandial
glucose measurements showed that glycohemoglobin levels,
macrosomia, neonatal hypoglycemia and cesarean deliveries were
significantly lower among those who had postprandial monitoring.
C. Monitoring Blood Glucose
28. Recently the new technology of continuous glucose monitoring (CGM) is available.
The CGM measures interstitial glucose levels in subcutaneous tissue within a range
of 50-400 mg/dl every 5 min.
CGM can accurately detect high postprandial blood glucose levels and nocturnal
hypoglycemic events that may go unrecognized by intermittent blood glucose
monitoring. However, CGM is not recommended to replace self-monitoring of
blood glucose, but the intermittent application of CGM could be used who have
problematic severe hypoglycemia (with or without impaired hypoglycemic
awareness) or who have unstable blood glucose levels (to minimize variability) or to
gain information about variability in blood glucose levels.
CONTINUED..
29. Pregnant women with pre-gestational or gestational DM are advised to keep
their fasting blood glucose level 5.3 mmol/L and 1-hour and 2-hour post-
prandial level 7.8 and 6.7 mmol/L respectively.
HbA1c (hemoglobin that is bound to glucose) levels are measured in all
women with gestational diabetes at the time of diagnosis to identify those
who may have pre-existing type 2 diabetes. HbA1c is lower in normal
pregnancy than in normal non pregnant women.
Other alternate new measure of glycemic control—fructosamine test has
been proposed. The fructosamine measures glycemic levels over a period of
2-3 weeks. However, it is less widely used due to lack of standardization.
D. Target Blood Glucose
30.
31. Insulin is started at a dosage of 0.7 units per kg per day (based on pre-
pregnancy weight), given in divided doses. A commonly used dosing
regimen includes two thirds of the total insulin dose to be given in the
morning, with the remainder before dinner.
Regular insulin, which is often used in pregnancy for the treatment of
diabetes, has some drawbacks: it starts its action from 30 to 60 min after
subcutaneous injection and it peaks too late (2-3 hour after injection) to
be very effective in postprandial control; in addition, its action also lasts
about 8-10 hour with an increased risk of postprandial hypoglycemia .
E. Insulin treatment
32. For this reason, insulin analogue started to be used in the last few years. Two
types of insulin analogues are used, rapid acting like lispro and aspart (bolus)
and long acting (basal) like glargine and detemir. Combining these two types
of insulin, basal-bolus therapy (BBT) is planned which most closely
simulates physiological insulin profiles and already in use in non-pregnant
patients. Now this BBT is also used in pregnant patients.
Use of insulin analogue in pregnancy is associated with decrease in HbA1c,
less maternal and neonatal hypoglycemia when compared to conventional
insulin (regular and NPH).
CONTINUED….
33. Traditionally insulin is considered as the gold standard
for management of GD. But it can be problematic for
some women as it is expensive and invasive.
For this a safe and effective oral agent for the treatment
of gestational diabetes is highly desired.. The sulfonylurea
glyburide is close to meeting these goals, with prospective
and retrospective studies
F. Oral Anti-diabetic agents
34. Fetal surveillance consists of screening for congenital anomalies,
monitoring for fetal well-being, and ultrasound assessment of fetal
growth.
The frequency of antenatal monitoring depends on the patient’s
degree of metabolic control, the type of therapy she is receiving
and the presence of other risk factors (hypertension).
This typically consists of twice-weekly non stress testing, with
amniotic fluid determinations beginning early in the third trimester.
Antenatal care
35. As women with pre gestational diabetes, the goal of intrapartum management is to
avoid maternal hyperglycemia and thus minimize the risk of neonatal hypoglycemia
after delivery.
Patients controlled by diet will not require intrapartum insulin and may simply need
glucose level monitoring on admission for delivery. During labor, patients with insulin-
requiring diabetes need capillary hourly monitoring of blood glucose levels. Published
protocols recommend low-dose insulin infusion for intrapartum management of
patients with insulin requiring diabetes.
A study suggests 5% dextrose infusion in active labor when maternal blood glucose
is below 100 mg/dl. For blood glucose concentrations exceeding 100 mg/dl, no
dextrose is included in the intravenously administered solution.
Intrapartum management
36. Contraception should be discussed and a commitment sought to a
program of planned pregnancies.
Low-dose oral contraceptive (OC) can be prescribed to GDM
patients with careful monitoring of their serum lipids and glucose
concentrations. If OCs is contraindicated barrier methods can be
used.
Postpartum Management
37. The main elements of the therapy include education, nutritional
therapy, exercise, and medical treatment.
The recommended daily calorie intake is 30 kcal/kg for women
with a BMI of 22-25, 24 kcal/kg for women with a BMI of 26-
29, and 12-15 kcal/kg for women with a BMI of >30.
This calorie intake may turn 75%-80% of women with GDM
into normoglycemic state
NEW APPROACHES IN THE TREATMENT
OF GESTATIONAL DIABETES
39. The use of oral anti-diabetics (OAD) during pregnancy is a
relatively new practice.
MAJOR ORALANTI-DIABETIC AGENTS
Biguanides: Metformin falls into this group. These agents
enhances peripheral glucose uptake, inhibit gluconeogenesis
and reduce plasma triglyceride concentrations. Metformin can
pass across the placenta. In a study that compared the use of
insulin versus metformin during pregnancy, use of metformin
did not result in an increase in perinatal complications
Continued…
40. Sulfonylureas: Glyburide (glibenclamide) and Glimepiride
fall into this group. These drugs increase insulin secretion and
peripheral sensitivity to insulin and decrease hepatic clearance
of insulin.
Glyburide is a second generation oral sulfonylurea
hypoglycemic agent. It acts by enhancing the release of insulin
from the pancreatic beta cells, therefore for its action, some
degree of pancreatic insulin-releasing function is required.
Continued…
41. Case study #1: Mrs. C
Mrs. C is a 22 year old primigravida coming for her first antenatal
checkup at 12 weeks of gestation.
On examination, she is 152 cm tall and weighs 69 kg. BMI, 30
kg/m2
She does not have a family history of diabetes.
Mrs. C had a fasting blood glucose done
Her results are as follows.
CASE STUDIES
42. Mrs. C undergoes repeat testing at 26 weeks’gestation.
Her results on the 75 gm glucose load (fasting) are as follows.
After 2 weeks, her results were as follows.
Continued…
43. Mrs. C is put on 4 units of rapid acting insulin before
breakfast and advised to monitor her blood glucose
daily. She does well.
After 2 weeks, her reports are as follows.
Continued…
44. Mrs. C is now on 6 units of NPH insulin at bedtime in addition to
4 units of rapid acting insulin before breakfast. She starts
complaining of excess hunger during the early hours of the
morning. Her reports are as follows.
Continued…
45. Her insulin dose has stabilized
NPH (neutral protamine Hagedorn) 8 units at bedtime
rapid acting insulin 6 units before breakfast, 4 units before
lunch and 4 units before evening meal.
Mrs. C goes into labour at 39 weeks.
Following delivery, blood glucose levels normalised and she
was able to stop insulin.
After 6 weeks, she underwent an OGTT, the results of
which are as follows.
Continued..
46.
47. Pre-eclampsia can be defined as ‘a blood pressure ≥140/90
mmHg after 20 weeks of gestation and involvement of one or
more organ systems with previously normal blood pressure.
PRE-ECLAMPSIA
48. 1. Preeclampsia (PE)-eclampsia (BP elevation after 20 weeks of
gestation with proteinuria or any of the severe features of
preeclampsia)
2. Chronic hypertension (CHTN, of any cause that predates
pregnancy)
3. Chronic hypertension with superimposed preeclampsia
(chronic hypertension in association with preeclampsia)
4. Gestational hypertension (GH: BP elevation >20 weeks of gestation
in the absence of proteinuria or any of the severe features of
preeclampsia)
Updated Classification
51. The exact mechanism of pre-eclampsia is unclear.
However, most current theories attribute pre-eclampsia
to poor placental perfusion, secondary to abnormal
placentation.
In normal placentation, the trophoblast invades the
myometrium and the spiral arteries of the uterus,
destroying the tunica muscularis media. This renders the
spiral arteries dilated and unable to constrict, providing the
pregnancy with a high flow, low resistance circulation.
PATHOPHYSIOLOGY
52. In pre-eclampsia, the remodelling of spiral arteries is incomplete.
A high resistance, low-flow uteroplacental circulation develops,
as the constrictive muscular walls of the spiral arterioles are
maintained.
The resultant increase in blood pressure, combined with
hypoxia and oxidative stress from inadequate uteroplacental
perfusion, leads to a systemic inflammatory
response and endothelial cell dysfunction (resulting in leaky blood
vessels).
Continue…
56. 1. Blood pressure
The NICE recommends keeping systolic blood pressure below
150 mmHg and diastolic blood pressure below 80–100 mmHg
and using labetalol as first-line treatment for hypertension.
There is an increasing trend toward tighter blood pressure
control in pre-eclampsia in those with essential or gestational
hypertension.
MANAGEMENT
57. Lifestyle modifications help lower
blood pressure
Modification Recommendation Lowers Systolic Blood
Pressure by (Range)
Weight reduction •Maintain normal body weight
•Body mass index (BMI) 18.5–24.9
kg/m2
5–20 mm Hg / 10 kg
4 mm Hg / 5 kg
DASH •Increase potassium (fruits and
vegetables) and calcium (dairy)
•DASH may be too high in protein,
potassium and phosphorus for CKD
8–14 mm Hg
Physical activity •At least 30 minutes most days 4–9 mm Hg
Sodium restriction •2,300 mg per day
•1,500 mg per day for hypertension,
diabetes, and CKD
2–8 mm Hg
58. Traditionally, severe hypertension has been treated with short
acting parenteral antihypertensive agents, most frequently
intravenous hydralazine or labetalol.
This is because of the speed of onset of action but means that
they require more intensive monitoring and can affect the fetus if
large shifts in blood pressure occur.
2. Oral Anti-hypertensives
59. A systematic review showed that, in most women, nifedipine
achieved treatment success similar to that of hydralazine or
labetalol. Less than 2% of women who received nifedipine
experienced hypotension.
There were no differences in adverse maternal or fetal outcomes.
Thus, the authors suggest that oral nifedipine is a suitable
treatment for severe hypertension in pregnancy and post-partum.
Continue….
60. Magnesium sulphate is recommended in severe preeclampsia
to prevent eclamptic seizures in the mother.
This is established in clinical practice for women with severe
hypertension or proteinuria or with mild to moderate
hypertension or proteinuria with the addition of clinical or
biochemical signs.
Magnesium sulphate
61. Preconcep
tion
Antenatal Delivery Postpartum Further
follow-up
Pre-
ecla
mps
ia
Assessment of
risk factors.
Hospital
admission at
diagnosis.
Antihypertensives
to be started if
BP>150/100.
Regular blood
investigations (2-
3/week)
Delivery
between
34-37
weeks,
depending
on
maternal/
foetal
condition
Initial monitoring
as inpatient, to be
discharged to the
community when
BP <149/99
with/without
treatment and
blood results are
stable
Medical review at
2 weeks, if
continuing
antihypertensives.
Otherwise at 6-8
weeks
MANAGEMENT STRATEGIES
62. Medication: Drug Class: Common Side-Effects:
Labetalol (1st line) Beta-blocker. Postural hypotension, fatigue, headache, nausea and
vomiting, epigastric pain.
Nifedipine Calcium channel blocker. Peripheral oedema, dizziness, flushing, headache,
constipation.
Methyldopa Alpha-agonist. Drowsiness, headache, oedema, GI disturbances, dry
mouth, postural hypotension, bradycardia, hepatotoxicity.
Anti-Hypertensive Medication Used in
Pregnancy
63. A 36 year old leady from AL-Mabeala G8P7, LMP:
15/5/2012 at 37weeks of gestation, EDD: 20/2/2013 referred
from HC for evaluation of High blood pressure in the last 5
days, avg of BP 130/90 mmHg. K/C/O PIH on labetalol.
P/C Hx:
She complains of headache since 2 weeks which is
bilateral, sharp in nature, progressive, intermittent,
aggravated by waking, not relived by paracetamol, and
it disturbing her daily activity. The headache associated
with nausea, vomiting, dizzenss, palpitation,
fatigability, labiality of mood. But there is no history of
fall or visual disturbance or abnormal movements. She
sleeps well.
CASE STUDY :
64. At the same episode she developed cough which was
intermittent, continuous all the day, productive of
yellow sputum, small amount, no blood, no foul smell.
It is Associated with difficulty in breathing in exertion.
No audible sounds or fever.
Also she complains of abdominal pain and cramps
(labour pain). And she noticed that her leg start to be
swelling in the last two days markedly.
She denied any urinary symptoms (pain, burning
sensation, UTI symptoms). Bowel habits are normal.
CONTINUE…
65. OBS Hx:
G8P7, all her previous pregnancies were uneventful (SVD, normal
baby weight, no complications) except for the last pregnancy were
she developed high BP at 37+ weeks of gestation and she was
induced.
After Last pregnancy she developed low Hb post partum (Hb
6mg/dL with blood loss 100 mL) received 2 units of blood post
delivery.
Current pregnancy: all her antenatal scans were normal, all
booking investigations were normal.
Booking Hb was 10,7 mg/dL; at 32-34 Hb was 8,8 mg/Dl
OGCT: 7.5
Anomaly scan normal
Las t scan on 2/2/2013: cephalic, AFI: 12cm, Doppler normal, efw
3.2Kg
CONTINUE…
66. Gestational diabetes is a condition that complicates significant
portion of the pregnancies and having significant consequences
on the health status of the mother and the baby.
It still remains unclear which treatment option would be more
appropriate when the women with a known GDM or diabetes
become pregnant. The use of oral anti-diabetic agents during
pregnancy is a relatively recent matter of debate. The current
reports suggest that metformin and glyburide could be used
during pregnancy.
CONCLUSION
67. Important evidence regarding the optimum methods of
diagnosis and management of pre-eclampsia is still emerging.
Until effective treatments are established, their biggest impact
will remain in women presenting with suspected disease.
Magnesium sulphate protects the preterm baby from
neurological insults, and a low threshold for use in preterm
pre-eclampsia is justified.
Continue…
68. American Diabetes Association. Diagnosis and Classification of
Diabetes Mellitus. Diabetes Care. 2011;34:62–9.
2. Lehnen H, Zechner U, Haaf T. Epigenetics of gestational diabetes
mellitus and offspring health: the time for action is in early stages of
life. Mol Hum Reprod. 2013;19:415–22. [PubMed]
3. O’Sullivan JB, Mahan CM. Criteria for oral glucose tolerance test in
pregnancy. Diabetes. 1964;13:278–85.
4. Metzger BE, Lowe LP, Dyer AR, Trimble ER, Chaovarindr U.
Hyperglycemia and adverse pregnancy outcomes. N Engl J
Med. 2008;358:1991–2002
5. Karakash SD, Einstein FH. Diabetes in pregnancy: glycemia control
guidelines and rationale. Curr Opin Endocrinol Diabetes
Obes. 2011;18:99–103.
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