Gestational diabetes mellitus

1
Gestational diabetes mellitus
Dr. Kanakamani Madhivanan, M.D., D.M.
(Endocrinology), Assistant Professor Department
of Endocrinology, Diabetes, Metabolism Christian
Medical College, Vellore
2
Plan of presentation

• 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

3
Introduction
4
Introduction

• 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

5
Introduction

• 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

6
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 gt 5.3
• a systolic BP gt 110 mm Hg
• BMI gt 30 kg/m2
• Fetal anomalies
• Clues for Type 1
• Lean
• DKA during pregnancy
• Severe hyperglycemia with large doses of insulin

7
Fuel metabolism in pregnancy
8
Fuel metabolism in pregnancy

• Goal is uninterrupted nutrient supply to fetus
• The metabolic goals of pregnancy are
• 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.

9
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

10
Glucose metabolism in pregnancy
FASTING accelerated starvation and esxaggerated
ketosis (maternal hypoglycemia, hypoinsulinemia,
hyperlipidemia, and hyperketonemia)
FED hyperglycemia, hyperinsulinemia,
hyperlipidemia, and reduced tissue sensitivity to
insulin
Fat
Hyperinsulinemia
Insulin resistance
Glucose
Aminoacids
Fetus
11

• 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

12
EPIdemiology AND Risk factors
13
Magnitude of problem Global

• 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
• Variability is partly because of the different
  criteria and screening regimens

14
Magnitude of the problem - India

• 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.  

15
Risk factors

• 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

16
Maternal and Fetal risks
17
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

18
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

19
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

20
Congenital anomalies

• 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

21

• 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

22
Caudal regression syndrome
23
Caudal regression syndrome
24
SCREENING AND DIAGNOSIS
25
Whom to screen ?

• 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

26
(No Transcript)
27
Low risk for GDM

• To satisfy all these criteria
• Age lt25 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.
• No history of abnormal glucose tolerance
• No history of poor obstetric outcome

28
High risk

• Marked obesity
• Prior GDM (30-50 risk for recurrence)
• Glycosuria
• Strong family history

29
When and how to screen?

• 24-28 weeks
• High risk
• First prenatal visit
• 50 g glucose loading test
• High risk women 3 hr GTT with 100 g glucose

30
(No Transcript)
31
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 federal
  standards for laboratory testing.

32
100 g GTT

• 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
• gt 2 values must be abnormal

Fasting gt 95 mg/dl
1-h gt 180 mg/dl
2-h gt 155 mg/dl
3-h gt 140 mg/dl
33
75 g GTT
ADA
WHO
Fasting gt 95 mg/dl
1-h gt 180 mg/dl
2-h gt 155 mg/dl
Fasting gt 95 mg/dl
OR OR
2-h gt 140 mg/dl
34
Whom and when to screen? Indian Scenario -The
DIPSI Guidelines

• 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

35
Management of gdm

36
MANAGEMENT ISSUES

• Patient education
• Medical Nutrition therapy
• Pharmacological therapy
• Glycemic monitoring SMBG and targets
• Fetal monitoring ultrasound
• Planning on delivery

37
Medical nutrition therapy

• Goals
• Achieve normoglycemia
• Prevent ketosis
• Provide adequate weight gain
• Contribute to fetal well-being
• Nutritional plan
• Calorie allotment
• Calorie distribution
• CH2O intake

38
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 gt30).
• 40 kcal per kg current weight per day in pregnant
  women who are less than BMI 22.

39
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 33-40 of
  calories, with the remainder divided between
  protein (about 20) and fat (about 40).
• With this calorie distribution, 75 to 80 percent
  of women with GDM will achieve normoglycemia.

40
Calorie distribution

• 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 10of 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 of
  total calories) are distributed, as needed, as
  snacks.

41
Monitoring BG

• Atleast 4 times
• Fasting and 3 one hr postprandial
• 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)

42
Monitoring BG

• 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 lt 5.1

43

• 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
• Glycosylated protein and fructosamine widely
  variable and not yet established

44
Glycemic targets (ACOG)

• 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
• ADA
• premeal 80-110
• 2 hr postmeal not more than 155

These are venous plasma targets, not glucometer
targets
45
PHARMACOLOGICAL INTERVENTION

• If the FPG at diagnosis is 120, can consider
  immediate therapy.
• Otherwise, MNT for 2 weeks
• If majority FPG (4/7) gt 95 or PP gt 120 then to
  start on insulin.

46
Insulin

• 15 need insulin
• 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 insulin
  resistance of pregnancy and obesity.

47
OHA in pregnancy

• 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
• Inconsistent data. ADA, ACOG, USFDA do not
  endorse.

48
OHA in pregnancy

• Tolbutamide and chlorpropamide
• Cross placenta. Fetal hperinsulinemia. Prolonged
  fetal hypoglycemia
• Glibenclamide
• Minimal transplacental transport
• Observational studies no excess anomalies or
  hypoglycemia
• Only RCT 404 women. Glib vs insulin. No
  difference

49

• 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 teratogenic in
  rat models

50
OHA in pregnancy

• 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
• Acarbose
• Two prelim studies
• Thiazolidinediones and GLP-1
• Not studied

51
Obstetric management
52
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)

53
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

54
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

55
Glycemic management during labour

• 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

56
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

57
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
58
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 feeds
• IV dextrose 6-8 mg/kg/min infusion
• Check for calcium, if seizure/irritability/RDS
• Examine infant for other congenital abnormalities

59
Future risks in mother and child
60
Future risks - Mother

• Atleast 6 weeks post delivery, 75 g OGTT for all
  GDM
• 90 normoglycemic
• Recurrence of GDM 30-60
• Older
• Multipara
• Weight gain interpregnancy
• Higher infant BW in index pregnancy
• IGT and T2DM
• 20 IGT postpartum
• 3.7 _at_ 6m , 4.9 _at_ 15m and 18.9 _at_ 9 y

61
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

62
Preconception counselling

• Diabetic mother glycemic control with
  insulin/SMBG
• Target HbA1c lt 7
• 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

63
Risk of developing DM in offspring

• Type 1 -
• Father - 1 in 17 risk
• Mother - 1 in 25 risk if, at the time of
  pregnancy, the mother is lt 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
• Both parents - 1 in 2.

64
Conclusion

• Gestational diabetes is a common problem in India
• Risk stratification and screening is essential in
  all Indian pregnant women
• Tight glycemic targets are required for optimal
  maternal and fetal outcome
• Patient education is essential to meet these
  targets
• Long term follow up of the mother and baby is
  essential

65

• THANKS