Diabetes in Pregnancy

1
Diabetes in Pregnancy

• Dr Thomas Paul MD DM (Endo)
• Dr. Mathew John MD DM(Endo)
• Department of Endocrinology
• Christian Medical College
• Vellore

2
Pregnancy may be complicated by diabetes in two
distinct forms

• Gestational diabetes mellitus (GDM) is defined
  as glucose intolerance of varying severity with
  onset or first recognition during pregnancy. This
  subset constitutes 90 of women with pregnancies
  complicated by diabetes. The most important
  perinatal concern in this group is macrosomia
  with resulting birth trauma. More than 50 women
  ultimately develop diabetes in the ensuing 20
  years and this is linked with obesity.
• Pre-gestational diabetes is diabetes that
  antedates pregnancy. Pregnancies which are
  complicated by pre-gestational diabetes, type-1
  or type-2, carry an additional risk to both
  mother and fetus beyond the effects on fetal
  growth and development in mid and late pregnancy.

3
Classification

• Pregestational diabetes A lady with known
  diabetes who conceives while on treatment with
  diet, oral hypoglycemic agents or insulin.
• Type 1 DM, Type 2 DM, Secondary DM
• Gestational diabetes mellitus is defined as
  glucose intolerance of variable degree with onset
  or first recognition during pregnancy. Some
  patients with fasting hyperglycemia detected
  early in pregnancy may be missed cases of
  diabetes that predated pregnancy. Women found
  early in pregnancy to have gestational diabetes
  are a high-risk subgroup.

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Magnitude of problem GDM

• GDM varies worldwide and among different racial
  and ethnic groups within a country.
• Variability is partly because of the different
  criteria and screening regimens
• Prevalence
• India 0.56 -6 (Ramachandran A et al
  1994 Hill et al., 2005)
• USA increased from 2.14.1 in the period
  1994 to 2002 with significant increases in all
  racial/ethnic groups (Dabelea et al., 2005).
• Native Americans, Asians, Hispanics,
  African-American, Aboriginal women are at higher
  risk (Ferrara, 2007).

Ramachandran A, Snehalatha C, Shymala P, Vijay V,
Viswanathan M. Prevalence of diabetes in pregnant
women--a study from southern India. Diabetes Res
Clin Pract. 19942571-74. Hill JC, Krisgnaveni
GV, Annamma I, Leary SD, Fall CH. Glucose
tolerance in pregnancy in South India
relationships to neonatal anthropometry. Acta
Obstet Gynecol Scand. 200584159-65 Dabelea, D,
Snell-Bergeon JK, Hartsfield CL, Bischoff KJ,
Hamman RF, McDuffie RS. Increasing Prevalence of
Gestational Diabetes Mellitus (GDM) Over Time and
by Birth Cohort. Diabetes Care 200528579-584 Fer
rara A Increasing prevalence of gestational
diabetes mellitus. Diabetes Care 200730S141-S146
5
Risk Factors for gestational diabetes screening

1. Strong family history of diabetes
2. Women who have given birth to large infants (gt4
   kg 8 lbs 13 oz)
3. History of recurrent fetal loss
4. Persistent glycosuria
5. Age gt 25 years
6. Past history of glucose intolerance or diabetes
   in a previous pregnancy

6
Risk Factors for gestational diabetes screening
7. Obesity overweight women (gt15 of
non-pregnant ideal body weight) 8. Ethnic group
with a high prevalence of diabetes (e.g. Pima
Indians, Asians, Hispanic) 9. History of
stillbirth, unexplained neonatal death,
congenital malformations, prematurity. 10.
History of pre-eclampsia or polyhydraminos 11.
Chronic hypertension 12. Recurrent severe
moniliasis or urinary tract infection 13. History
of traumatic delivery with an associated
neurological disorder in the infant
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Whom to screen?

• Risk stratification
• Low risk no screening
• Average risk at 24-28 weeks
• High risk as soon as possible

Screening is ideally initiated between the 24th
and 28th weeks of pregnancy or earlier if any of
the risk factors are present.
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Low risk for GDM

• Age lt25 years
• Weight normal before pregnancy
• Member of an ethnic group with a low prevalence
  of GDM
• No known diabetes in first-degree relatives
• No history of abnormal glucose tolerance
• No history of poor obstetric outcome

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High risk for GDM
Intermediate risk for GDM
Must exhibit one risk factor from the list in
slide 5.

• Marked obesity
• Prior GDM
• Glycosuria
• Strong family history
• Ethnic group with high diabetes prevalence

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• All Indian women and women of Indian origin
  should be screened for gestational diabetes
  mellitus
• as they belong to a high risk ethnicity

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Screening test

• Glucose Challenge Test (GCT) An excellent
  screening test for gestational diabetes is the
  measurement of plasma glucose 1 hour after
  ingesting 50 g of glucose.
• A plasma glucose level obtained one hour after a
  50 g glucose load administered at any time of the
  day without regard to the time since the last
  meal, has become a well validated and widely
  applied screening procedure for women between 24
  and 28 weeks of gestation.
• Using a cut-off value gt 140 mg/dl identifies 80
  women with GDM
• Using a cut-off value gt 130 mg/dl identifies 90
  women with GDM
• Women with elevated GCT values require a
  diagnostic oral glucose tolerance test

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Screening test
Oral Glucose Tolerance Test (OGTT) Measurement
of plasma glucose after ingesting 100 g of
glucose.
Timing of measurement National Diabetes Data Group (1979) Carpenter and Coustan (CC) 1982
Fasting 105 mg/dl 95 mg/dl
1 hour 190 mg/dl 180 mg/dl
2 hour 165 mg/dl 155 mg/dl
3 hour 145 mg/dl 140 mg/dl
gt 2 values must be abnormal for at least 3 days
prior to the test, the patient should have an
unrestricted diet and unlimited physical
activity. The patient should fast for 8 hours
before the test. The CC criteria detects 54 more
women with GDM than the NDDG criteria
Classification and diagnosis of diabetes
mellitus and other categories of glucose
intolerance National Diabetes Data Group.
Diabetes 19792810391057 Carpenter MW, Coustan
DR. Criteria for screening tests for gestational
diabetes. Am J Obstet Gynecol. 1982144768-73.
13

Urine monitoring
Urine glucose monitoring is not useful in
gestational diabetes mellitus Urine ketone
monitoring may be useful in detecting
insufficient caloric or carbohydrate intake in
women treated with calorie restriction
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Effects of GDM on the fetus

• Congenital abnormalities
• Neonatal hypoglycemia
• Macrosmia (big baby syndrome gt 4 Kg or gt8 lb 13
  oz)
• Jaundice
• Polycythemia / hyperviscosity syndrome
• Hypocalcemia, hypomagnesemia
• Birth trauma (due to macrosmia and shoulder
  dystocia)
• Prematurity
• Hyaline membrane disease
• Apnea and bradycardia

The risk of fetal anomalies is not increased in
GDM patients. However, the risks of unexplained
still births (during the last 4-8 weeks of
gestation) are similar to pre-gestational
diabetes.
15
Effects of GDM on neonates
Respiratory distress Hypoglycemia Hypocalcemia Hyp
erbilirubinemia Cardiac Hypertrophy Long term
effects on cognitive development
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Macrosomic infant
Macrosomia (large for gestational age or big baby
syndrome) (birth weight gt90 percentile for
gestational age) Macrosomia is a result of
persistent maternal hyperglycemia leading to
fetal hyperglycemia and prolonged fetal
hyperinsulinism. This stimulates excessive
somatic growth mediated by insulin-like growth
factors (IGFs). Macrosomia affects all organs
except the brain.
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Congenital abnormalities due to GDM

• Cardiac (most common) transposition of great
  vessels, Ventricular septal defect, Atrial septal
  defect
• Central nervous system (7.2) spina bifida,
  Anencephaly, hydrocephalus
• Skeletal cleft lip/palate, caudal regression
  syndrome
• Genitourinary tract ureteric duplication
• Gastrointestinal anorectal atresia
• Renal agenesis, Duplex ureters, Cystic Kidney
• Situs inversus

Poor glycemic control at time of conception risk
factor
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Caudal regression syndrome (abnormal development
of lower spine)
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Caudal regression syndrome
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Effects of GDM on the mother

• Pre-eclampsia affects 10-25 of all pregnant
  women with GDM
• Infections high incidence of chorioamnionitis
  and postpartum endometritis
• Postpartum bleeding high incidence caused by
  exaggerated uterine distension
• Cesarian section more common due to fetal
  macrosmia and cephalo-pelvic disproportion
• Weight gain
• Hypertension
• Miscarriages
• Third trimester fetal deaths
• Long term risk of type-2 diabetes mellitus

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Effect of pregnancy on diabetes

• More insulin is necessary to achieve metabolic
  control
• Progression of retinopathy esp. severe
  proliferative retinopathy
• Progression of nephropathy especially if renal
  failure
• Increased risk of Coronary artery disease, and a
  high risk of maternal death in post MI patients
• Cardiomyopathy

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Patient educationCornerstone in GDM management

• Instruct mother about maternal and fetal
  complications
• Medical Nutrition therapy
• Glycemic monitoring teach mother about self
  monitored blood glucose measurement and glycemic
  targets
• Pre-conception counseling
• Fetal monitoring ultrasound
• Planning on delivery
• Long term risks

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Glycemic control targets

• Tight glycemic control can reduce fetal risk.
  But, stringent glycemic control puts the mother
  at increased risk of hypoglycemic events and the
  fetus at risk of being small-for-gestational age.
  
• American Diabetes Association Recommendations

Fasting whole blood glucose lt95 mg/dl
1 hr postprandial blood glucose lt140 mg/dl
2 hr postprandial blood glucose lt120 mg/dl
These are venous plasma targets, not glucometer
targets
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Why these tight glycemic targets?

• Prospective study in type-1 patients with
  pregnancy

Fasting blood sugar Macrosomia
gt105 mg/dl 28.6
95-105 10
lt95 mg/dl 3
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Self monitored blood glucose (SBMG)

• 4 times/day minimum, fasting and 1 to 2 hours
  after start of meals
• Maintain log book
• Use a memory meter
• Calibrate the glucometer frequently

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Medical Nutrition and Exercise therapy

• provide necessary nutrients for mother and fetus
  to ensure adequate gestational weight gain
• control glucose levels
• prevent starvation ketosis
• aerobic exercise, exercise that does not stress
  the trunk

Current weight in relation to ideal body weight Daily caloric intake (kcal/kg) Recommended pregnancy weight gain (kg)
lt80-90 36-40 28-40
80-120 (ideal) 30 25-35
120-150 24 15-25
gt150 12-18 15-25
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Medical nutrition therapy

• Approximately 30 kcal/kg of ideal body weight
• gt 40-45 should be carbohydrates
• 6-7 meals daily (3 meals, 3-4 snacks). Bed time
  snack to prevent ketosis
• Calories guided by fetal well being/maternal
  weight gain/blood sugars/ ketones
• Energy requirements during the first 6 months of
  lactation require an additional 200 calories
  above the pregnancy meal plan

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Insulin in GDM

• Insulin used if fasting blood glucose gt105 mg/dl
  or 1 hr postprandial blood glucose gt120 mg / dl
  on a diet
• Use basal bolus regime or pre-mixed insulin
• Short acting insulins (e.g. Lispro and Aspart)
  can be used to achieve postprandial control
• Long acting insulins (Glargine and Determir) are
  NOT licensed in pregnancy
• Insulin requirements increase by 50 from 20-24
  weeks to 30-32 weeks, after which insulin needs
  often stabilize.

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Oral Hypoglycemic agents
Glyburide is a clinically effective alternative
to insulin in GDM (Langer et al. 2000) Metformin
may be effective in GDM (Ratner et al., 2008
Coustan, 2007)
Langer O, Conway DL, Berkus MD, Xenakis EM,
Gonzales O. A comparison of glyburide and insulin
in women with gestational diabetes mellitus. N
Engl J Med. 20003431134-8 Ratner RE, Christophl
CA, Metzger BE, Dabalea D, Bennett PH, Pi-Sunyer
X, Fowler S, Kahn SE, Diabetes Prevention Program
Research Group. Prevention of diabetes in women
with a history of gestational diabetes effects
of metformin and lifestyle interventions. J Clin
Endocrinol Metab. 2008934774-9 Coustan DR
Pharmacological management of gestational
diabetes an overview. Diabetes Care. 200730
Suppl 2S206-8.
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Preconception counseling
All women with pre-existing type-1 or type-2
diabetes, when planning on pregnancy, should
receive pre-conception counseling so that they
understand the importance of achieving
near-normal blood glucose before conception to
reduce the risk of congenital malformations and
spontaneous abortions.

• Assess maternal and fetal risk
• Mother should learn self-administration of
  insulin and regular monitoring of blood glucose.
• Target HbA1c lt 7
• Emphasize diet and exercise
• Folic acid supplementation 5 mg/day
• Ensure no transmissible diseases HBsAg, HIV,
  rubella
• Try and achieve normal body weight
  diet/exercise
• Stop drugs oral hypoglycemic drugs, ACE
  inhibitors, beta blockers and potentially
  teratogenic drugs

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Clinical parameters checked at each visit

• Medications
• Pre-pregnancy weight
• Weight gain
• Edema
• Pallor
• Thyroid enlargement
• Blood pressure
• Fundal height

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Laboratory parameters to be monitored at each
visit

• Hemoglobin
• Blood Sugar
• HbA1C (first trimester only)
• Urine microscopy and albumin
• Thyroid function (if goiter present)

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Fetal monitoring

• Baseline ultrasound fetal size
• Ultrasound evaluation of neural tube defects and
  other congenital malformations should begin by
  15-21 weeks of
• At 18-22 weeks fetal anatomic survey, major
  malformations
• At 20-22 weeks fetal echocardiogram for cardiac
  defects
• At 26 weeks onwards ultrasound to evaluate
  fetal growth and amniotic fluid volume
• Third trimester Fetal surveillance to reduce
  risk of still birth include non-stress test,
  biophysical profile, maternal monitoring of fetal
  activity, frequent USG for accelerated growth
• abdominal head circumference

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Timing of delivery

• Small risk of late intra-uterine death even with
  good glycemic control
• Delivery usually at 38 weeks
• Beyond 38 weeks, increased risk of intrauterine
  death without an increase in RDS

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Management of labor and delivery

• Vaginal delivery preferred
• Cesarian section only for routine obstetric
  indication
• GDM alone is not an indication !
• gt 4.5 Kg fetus Cesarean delivery may reduce the
  likelihood of brachial plexus injury in the
  infant
• Unfavorable condition of the cervix is a problem
• Maintain euglycemia during labor
• Maternal hyperglycemia in labor fetal
  hyperinsulinemia and worsen fetal acidosis
• Maintain sugars 80-120 mg/dl (capillary
  70-110mg/dl )
• Feed patient the routine GDM diet
• Maintain basal glucose requirements
• Monitor sugars 1-4 hrly intervals during labour
• Give insulin only if blood sugar gt120 mg/dl

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Glycemic management during labour

• Later stages of labour start dextrose to
  maintain basal nutritional requirements 150-200
  ml/hr of 5 dextrose
• Elective Cesarian section check fasting blood
  sugar if within target range no insulin is
  needed start dextrose drip
• Continue hourly self monitored blood glucose
• Post delivery keep patients on dextrose-normal
  saline till fed
• No insulin unless sugars more than normal ( not
  GDM targets ! )

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Post partum follow up

• Check blood sugars before discharge
• Breast feeding helps in weight loss
• Lifestyle modification exercise, weight
  reduction
• Oral glucose tolerance test at 6-12 weeks
  postpartum classify patients into
  normal/impaired glucose tolerance and diabetes
• Preconception counseling for next pregnancy

Increased risk of cardiovascular disease, future
diabetes and dyslipidemia
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Immediate management of neonate

• Hypoglycemia 50 of macrosomic infants
• 515 optimally controlled GDM
• Starts when the cord is clamped
• Exaggerated insulin release secondary to
  pancreatic ß-cell hyperplasia
• Increased risk blood glucose during labor and
  delivery exceeds 90 mg/dl

Anticipate and treat hypoglycemia in the infant
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Management of neonate

• Hypoglycemia lt40 mg/dl
• Encourage early breast feeding
• If symptomatic give a bolus of 2- 4 ml/kg, IV,
  10 dextrose
• Check after 30 minutes, start feeding
• IV dextrose 6-8 mg/kg/min infusion
• Check for calcium, if seizure/irritability/RDS
• Examine infant for other congenital abnormalities

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Long term risk offspring

• Increased risk of obesity and abnormal glucose
  tolerance due to changes in fetal islet cell
  function
• Encourage breast feeding less chance of obesity
  in later life
• Lifestyle modification

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Conclusion

• Gestational diabetes is a common problem in
  worldwide
• Risk stratification and screening is essential
  in all pregnant women, particularly those from
  ethnicities with increased risk
• Tight glycemic targets are required for optimal
  maternal and fetal outcome
• Patient education is essential to meet targets
• Long term follow up of the mother and baby is
  essential

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Courtesy MSNBC News Services Jan. 24, 2005
17 pound baby born to Brazilian diabetic mother