Transcript diabetes-pregnancy

Dr. Kanakamani Madhivanan, M.D., D.M. (Endocrinology),
Assistant Professor
Department of Endocrinology, Diabetes, Metabolism
Christian Medical College, Vellore
Plan of presentation
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Introduction
Physiology of fuel metabolism in normal
pregnancy
Pathophysiology of GDM
Epidemiology of GDM
Screening and diagnosis
Maternal and fetal risks
Management of GDM
Obstetric management
Introduction
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Global increase in prevalence of DM
Individual importance - Hyperglycemia in
pregnancy has adverse effects on both
mother and fetus
Public health importance – rising epidemic
of DM in part attributed to the diabetic
pregnancies
Prevention of type 2 DM should start
intrauterine and continue throughout life
Introduction
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Gestational diabetes (GDM) is defined as
any degree of impaired glucose tolerance of
with onset or first recognition during
pregnancy .
 Many are denovo pregnancy induced
 Some are type 2 ( 35-40%)
 10% have antibodies
Introduction
Difficult to distinguish pregestational Type 2 DM and
denovo GDM
 Fasting hyperglycemia
 blood glucose greater than 180 mg/dL on OGT
 acanthosis nicgrans
 HbA1C > 5.3%
 a systolic BP > 110 mm Hg
 BMI > 30 kg/m2
 Fetal anomalies
 Clues for Type 1
 Lean
 DKA during pregnancy
 Severe hyperglycemia with large doses of insulin
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Fuel metabolism in pregnancy
Goal is uninterrupted nutrient supply to
fetus
 The metabolic goals of pregnancy
are
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 1) in early pregnancy to develop
anabolic stores to meet metabolic
demands in late pregnancy
 2) in late pregnancy to provide fuels
for fetal growth and energy needs.
Glucose metabolism in
pregnancy
Early pregnancy
 E2/PRL stimulates b cells –Insulin sensitivity
same and peripheral glucose utilisation – 10% fall
in BG levels
 Late pregnancy
○ Fetoplacental unit extracts glucose and
aminoacids, fat is used mainly for fuel
metabolism
○ Insulin sensitivity decreases progressively upto
50-80% during the third trimester
○ variety of hormones secreted by the placenta,
especially hPL and placental growth hormone
variant, cortisol, PRL,E2 and Prog
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Glucose metabolism in
pregnancy
FASTING
accelerated
starvation and
esxaggerated
ketosis
(maternal
hypoglycemia,
hypoinsulinemia,
hyperlipidemia,
and
hyperketonemia)
Fat
Insulin resistance
Glucose
Hyperinsuli
nemia
Aminoacids
Fetus
FED
hyperglycemia,
hyperinsulinemia,
hyperlipidemia,
and reduced
tissue sensitivity
to insulin
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24-hour insulin requirement before conception is approximately 0.8 units /
kg.
In the first trimester, the insulin requirement rises to 0.7units / kg of the
pregnant weight – more unstable glycemia with a tendency to low fasting
plasma glucose and high postprandial excursions and the occurrence of
nocturnal hypoglycemia
By the second trimester, the insulin requirement is 0.8 units per kilogram.
From 24th month onwards steady increase in insulin requirement and
glycemia stabilises
By third trimester the insulin requirement is 0.9 - 1.0 unit /kg pregnant
weight per day
Last month – may be a decrease in insulin and hypoglycemias esp.
nocturnal
Magnitude of problem: Global
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Prevalence of GDM varies worldwide and
among different racial and ethnic groups
within a country
○ America – white women (3.9%) and Asian (8.7%)
○ Europe – 0.6% to 3.6%
○ Australia – 3.6% to 4.7% (Indian women – 17.7%)
○ China – 2.3%; Japan – 2.9%
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Variability is partly because of the
different criteria and screening regimens
Magnitude of the problem India
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Chennai, hospital based, universal screening –
18.9% had FPG ≥ 126 and PPPG ≥ 140.
 Trivandrum – 15%
 Bangalore – 12%
 Erode – 18.8%
Chennai, community based, universal screning,
17.8% in urban, 13.8% in semi urban and 9.9% in rural
areas.
Chennai : 0.56%
Mysore Parthenon Study: 6%
Maharashtra, hospital based, selective
screening – 7.7% had GDM; 13.9% had IGGT.
Risk factors
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A family history of diabetes, especially in first degree relatives
Prepregnancy weight ≥110% of ideal body weight or body mass index over
30 kg/m2 or significant weight gain in early adulthood, between
pregnancies, or in early pregnancy
Age greater than 25 years
Previous delivery of a baby greater than 4.1 kg
Personal history of abnormal glucose tolerance
Member of an ethnic group with higher than the background rate of type 2
diabetes (in most populations, the background rate is approximately 2
percent)
Previous unexplained perinatal loss or birth of a malformed child
Maternal birthweight greater than 4.1 kg or less than 6 pounds 2.7 kg
Glycosuria at the first prenatal visit
Polycystic ovary syndrome
Current use of glucocorticoids
Essential hypertension or pregnancy-related hypertension
Maternal complications
Worsening retinopathy – 10% new DR, 20%
mild NPDR and 55% mod-severe NPDR
progresses
 Worsening proteinuria. GFR decline depends
on preconception creatinine and proteinuria
 Hypertension and Cardiovascular disease
 Neuropathy – No worsening (gastroparesis,
nausea, orthostatic dizziness can be
worsened)
 Infection
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Maternofetal complications
Macrosomia: 63 percent
 Cesarean delivery: 56 percent
 Preterm delivery: 42 percent
 Preeclampsia: 18 percent
 Respiratory distress syndrome: 17 percent
 Congenital malformations: 5 percent
 Perinatal mortality: 3 percent
 Spontaneous abortion, third trimester fetal deaths,
Polyhydramnios, preterm birth, ?adverse
neurodevelopmental outcome
 Risk for type 2 DM
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Neonatal complications
Morbidity associated with preterm birth
 Macrosomia ± birth injury (shouldeer dystocia, brachial
plexus injury)
 Polycythemia and hyperviscosity
 Hyperbilirubinemia
 Cardiomyopathy
 Hypoglycemia and other metabolic abnormalities
(hypocalcemia, hypomagnesemia)
 Respiratory problems
 Congenital anomalies
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Congenital anomalies
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2/3rd CVS or CNS,– 13-20 times common
Cardiac( including great vessel anomalies) : most
common
Central nervous system (spina bifida/anencephaly) :
7.2%
Skeletal: cleft lip/palate, caudal regression syndrome
Genitourinary tract: ureteric duplication
Gastrointestinal : anorectal atresia
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Skeletal and central nervous system
 Caudal regression syndrome
 Neural tube defects excluding anencephaly
 Anencephaly with or without herniation of neural elements
 Microcephaly
Cardiac
 Transposition of the great vessels with or without ventricular
 Ventricular septal defects
 Coarctation of the aorta with or without ventricular septal defects or patent ductus arteriosus
 Atrial septal defects
 Cardiomegaly
Renal anomalies
 Hydronephrosis
 Renal agenesis
 Ureteral duplication
Gastrointestinal
 Duodenal atresia
 Anorectal atresia
 Small left colon syndrome
Caudal regression syndrome
Caudal regression syndrome
Whom to screen ?
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No consensus
 recommended screening ranges from
selective screening of average- and high-risk
individuals to universal diagnostic testing of
the entire population dependent on the risk
of diabetes in the population.
Risk stratification based on certain variables
Low risk : no screening
Average risk: at 24-28 weeks
High risk : as soon as possible
Low risk for GDM
To satisfy all these criteria
Age <25 years
 Not a member of an ethnic group with high prevalence of GDM
(not Hispanic, Native American/Alaskan,
Asian/Pacific Islander, African American)
 Normal prepregnancy body weight (not 20% or more
over desired body weight or BMI 27 kg/m2 or more)
 No family history of diabetes in first-degree relatives.
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No history of abnormal glucose tolerance
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No history of poor obstetric outcome
High risk
 Marked obesity
 Prior GDM (30-50% risk for recurrence)
 Glycosuria
 Strong family history
When and how to screen?
24-28 weeks
 High risk
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 First prenatal visit
50 g glucose loading test
 High risk women – 3 hr GTT with 100 g
glucose
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50 g GTT
A 50-g oral glucose load is given without
regard to the time elapsed since the last
meal and plasma or serum glucose is
measured one hour later
 A value ≥130 mg/dL is considered
abnormal ; we use ≥130 mg/dL as the
threshold for our patients.
 Capillary blood should not be used for
screening unless the precision of the
glucose meter is known, it has been
correlated with simultaneously drawn
venous plasma samples, and has met
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100 g GTT
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Oral glucose tolerance test ( OGTT) with 100 gm
glucose
Overnight fast of at least 8 hours
At least 3 days of unrestricted diet and unlimited
physical activity
> 2 values must be abnormal
Fasting
> 95 mg/dl
1-h
> 180 mg/dl
2-h
> 155 mg/dl
3-h
> 140 mg/dl
75 g GTT
ADA
WHO
Fasting
> 95 mg/dl
1-h
> 180 mg/dl
2-h
> 155 mg/dl
Fasting
> 95 mg/dl
OR
2-h
> 140 mg/dl
Whom and when to screen?
Indian Scenario -The DIPSI
Guidelines
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75 gm GCT with single PG at 2 hrs –
 ≥ 140 mg/dL is GDM
 ≥ 120 mg/dL is DGGT
Universal screening
 First trimester, if negative at 24 – 28
weeks and then at 32 – 34 weeks
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MANAGEMENT ISSUES
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Patient education
Medical Nutrition therapy
Pharmacological therapy
Glycemic monitoring: SMBG and targets
Fetal monitoring: ultrasound
Planning on delivery
Medical nutrition therapy
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Goals
 Achieve normoglycemia
 Prevent ketosis
 Provide adequate weight gain
 Contribute to fetal well-being
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Nutritional plan
 Calorie allotment
 Calorie distribution
 CH2O intake
Calorie allotment
30 kcal per kg current weight per day in
pregnant women who are BMI 22 to 25.
 24 kcal per kg current weight per day in
overweight pregnant women (BMI 26 to
29).
 12 to 15 kcal per kg current weight per
day for morbidly obese pregnant women
(BMI >30).
 40 kcal per kg current weight per day in
pregnant women who are less than BMI
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Carb intake
Postprandial blood glucose concentrations
can be blunted if the diet is carbohydrate
restricted. Complex carbohydrates, such as
those in starches and vegetables, are more
nutrient dense and raise postprandial
blood glucose concentrations less than
simple sugars.
 Carbohydrate intake is restricted to 3340% of calories, with the remainder divided
between protein (about 20%) and fat
(about 40%).
 With this calorie distribution, 75 to 80
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Calorie distribution
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Variable opinion
Most programs suggest three meals and three
snacks; however, in overweight and obese women
the snacks are often eliminated
 Breakfast — The breakfast meal should be small
(approximately 10%of total calories) to help
maintain postprandial euglycemia.
Carbohydrate intake at breakfast is also limited
since insulin resistance is greatest in the
morning.
 Lunch — 30% of total calories
 Dinner — 30% of total calories
 Snacks — Leftover calories (approximately 30%
Monitoring BG
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Atleast 4 times
 Fasting and 3 one hr postprandial
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Pre vs postprandial monitoring
 Better glycemic control (HbA1c value 6.5
versus 8.1 percent)
 A lower incidence of large-for-gestational
age infants (12 versus 42 percent)
 A lower rate of cesarean delivery for
cephalopelvic disproportion (12 versus 36
percent)
Monitoring BG
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Home monitoring
 Maintain log book
 Use a memory meter
 Calibrate the glucometer frequently
HbA1C
 Ancillary test for feedback to the patient
 Lower values when compared to nonpregnant state –
lower BG and increase in red cell mass and slight
decrease in life span – measured every 2-4 weeks
 Target < 5.1%
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Studies report no to moderate correlations
between HbA1 and different components of the
glucose profile when an HbA1 result of 4% to 5%
includes a capillary blood glucose range of 50 to
160 mg/dL.
Levels of HbA1c are related to the rate of
congenital anomalies and spontaneous early
abortions in pre-existing diabetes, but the use of
this measure, which retrospectively reflects
glycemic profile in the last 10 weeks, for treatment
evaluation in GDM is questionable. In addition,
the association between glycosylated hemoglobin
and pregnancy outcome in GDM or prediction of
macrosomia is poor
Glycemic targets (ACOG)
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ACOG
 Fasting venous plasma ≤ 95 mg/dl
 1 hour postprandial ≤ 140 mg/dl
 2 hour postprandial ≤ 120 mg/dl
 Pre-meal ≤ 100 mg/dl
 A1C ≤ 6%
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ADA
 premeal 80-110
 2 hr postmeal not more than 155
These are venous plasma targets, not glucometer targets
PHARMACOLOGICAL
INTERVENTION
If the FPG at diagnosis is ≥ 120, can
consider immediate therapy.
 Otherwise, MNT for 2 weeks
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 If majority FPG (4/7) > 95 or PP > 120 then
to start on insulin.
Insulin
 ≈ 15% need insulin
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Total dose varies. ≈ 0.7 to 2 units per kilogram (present
pregnant weight)
FBG high – Night NPH ≈ 0.2 units/kg
PPBG high – bolus ≈ 1.5 units/10 gm CH2O for
breakfast and ≈ 1 unit /10 gm CH2O for lunch and
dinner
If both pre and postprandial BG high or if the woman's
postprandial glucose levels can only be blunted if
starvation ketosis occurs - four injection/day regimen.
 Total 0.7 unit/kg up to week 18
 0.8 unit/kg for weeks 18 to 26
 0.9 unit/kg for weeks 26 to 36
 1. unit/kg for weeks 36 to term.
 In a morbidly obese woman, the initial doses of insulin may need
to be increased to 1.5 to 2. units/kg to overcome the combined
OHA in pregnancy
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Systematic review by John Hopkins
University
 maternal glucose levels did not differ
substantially between gravidae treated with
insulin versus those treated with oral
glucose-lowering agents
 there was no consistent evidence of an
increase in any adverse maternal or neonatal
outcome with use of glyburide, acarbose, or
metformin compared with use of insulin
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Inconsistent data. ADA, ACOG, USFDA
do not endorse.
OHA in pregnancy
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Tolbutamide and chlorpropamide
 Cross placenta. Fetal hperinsulinemia.
Prolonged fetal hypoglycemia
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Glibenclamide
 Minimal transplacental transport
 Observational studies – no excess anomalies
or hypoglycemia
 Only RCT – 404 women. Glib vs insulin. No
difference
second-generation sulfonylureas
especially glyburide, do not significantly
cross the diabetic or nondiabetic
placenta. Fetal concentrations reached
no more than 1% to 2% of maternal
concentrations.
 tolbutamide diffused across the placenta
most freely, followed by
chlorpropamide, then glipizide, with
glyburide crossing the least.
 Metformin crosses placenta – not
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OHA in pregnancy
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Metformin
 Category B
 No adverse outcome after first trimester
 Second, third trimester safe and effective
 Vs. insulin – no serious adverse effects
 No studies vs. glibenclamide
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Acarbose
 Two prelim studies
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Thiazolidinediones and GLP-1
 Not studied
Fetal monitoring
Baseline ultrasound : fetal size
 At 18-22 weeks: major malformations
fetal echocardiogram
 26 weeks onwards: growth and liquor volume
 III trimester: frequent USG for accelerated growth
( abdominal: head circumference)
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Timing of delivery
Small risk of late IUD even with good control
 Delivery at 38 weeks – to avoid late still birth and fetal
growth leading to shoulder dystocia
 Vaginal delivery: preferred
 Caesarian section only for routine obstetric indication
just GDM is not an indication !
 Unfavorable condition of the cervix is a problem
 4500 grams, cesarean delivery may reduce the
likelihood of brachial plexus injury in the infant
(ACOG). Assessing fetal weight accurately is a problem
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Management of labor and delivery
Maternal hyperglycemia in labor: fetal hyperinsulinemia,
worsen fetal acidosis and neonatal hypoglycemia
 Insulin requirements come down
 Maintain sugars: 70-90 mg/dl
 Routine GDM diet
 Maintain basal glucose requirements
 Monitor sugars 1-4 hrly intervals during labour
 Give insulin as infusion only if sugars more than 120 mg/dl
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Glycemic management during
labour
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Later stages of labour: start dextrose to maintain
basal nutritional requirements: 150-200 ml/hr of
5% dextrose
Elective LSCS: check FBS, if in target no insulin,
start dextrose drip
Continue hourly SMBG
Post delivery keep patients on dextrose-normal
saline till fed
No insulin unless sugars more than normal
nonpregnant levels
Post partum follow up
Check BG before discharge
 Breast feeding: helps in weight loss. Insulin,
tolbutamide compatible. Chlropropamide secreted small
amounts – watch for hypoglycemia in infant. Glyburide
and glipizide not secreted Metformin secreted - no
adverse effects
 Lifestyle modification: exercise, weight reduction
 OGTT at 6-12 weeks postpartum: classify patients into
normal/impaired glucose tolerance and diabetes
 Contraception – low dose EP can be used. Progestin only
pills shown to increase risk of T2DM in GDM
 Preconception counseling for next pregnancy
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Immediate management of neonate
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Hypoglycemia : 50 % of macrosomic infants
5–15 % optimally controlled GDM
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Starts when the cord is clamped
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Exaggerated insulin release secondary to
pancreatic ß-cell hyperplasia
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Increased risk : blood glucose during labor and
delivery exceeds 90 mg/dl
Anticipate and treat hypoglycemia in the infant
Management of neonate
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Hypoglycemia <40 mg/dl
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Encourage early breast feeding
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If symptomatic give a bolus of 2- 4 ml/kg, IV 10%
dextrose
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Check after 30 minutes, start feeds
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IV dextrose : 6-8 mg/kg/min infusion
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Check for calcium, if seizure/irritability/RDS
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Examine infant for other congenital abnormalities
Future risks - Mother
Atleast 6 weeks post delivery, 75 g OGTT for
all GDM
 ≥ 90% normoglycemic
 Recurrence of GDM – 30-60%
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 Older
 Multipara
 Weight gain interpregnancy
 Higher infant BW in index pregnancy
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IGT and T2DM
 20% IGT postpartum
 3.7% @ 6m , 4.9% @ 15m and 18.9% @ 9 y
Who will progress to DM?
WC and BMI – stronset predictors
 Autoantibodies
 DM at earlier gestational age
 Gestational requirement of insulin
 Higher FBG
 Higher BG on OGTT
 Neonatal hypoglycemia
 Recurrent GDM
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Preconception counselling
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Diabetic mother : glycemic control with
insulin/SMBG
Target: HbA1c < 7%
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Folic acid supplementation: 5 mg/day
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Ensure no transmissible diseases: HBsAg, HIV,
rubella
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Try and achieve normal body weight: diet/exercise
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Stop drugs : oral hypoglycemic drugs, ACE
inhibitors, beta blockers
Risk of developing DM in
offspring
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Type 1  Father - 1 in 17 risk
 Mother - 1 in 25 risk if, at the time of pregnancy, the
mother is < 25 years of age but a 1 in 100 risk if the
mother is 25 years of age or older.
 These risks are doubled if the affected parent developed
diabetes before age 11.
 Both parents have type 1 diabetes - 1 in 10 - 1 in 4.
Type 2 polyglandular autoimmune syndrome – 50%
Type 2
 Single parent - 1 in 7 if the parent was diagnosed before
age 50 and 1 in 13 if the parent was diagnosed after age
50.
 There is some evidence that the offspring's risk is greater
when the parent with type 2 diabetes is the mother. I
Conclusion
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Gestational diabetes is a common problem in India
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Risk stratification and screening is essential in all
Indian pregnant women
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Tight glycemic targets are required for optimal
maternal and fetal outcome
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Patient education is essential to meet these targets
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Long term follow up of the mother and baby is
essential
THANKS