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 > 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

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
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 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 weeks
High risk : as soon as possible

27. 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.
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

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
> 2 values must be abnormal
Fasting
> 95 mg/dl
1-h
> 180 mg/dl
2-h
> 155 mg/dl
3-h
> 140 mg/dl

33. 75 g GTT ADA WHO Fasting > 95 mg/dl 1-h > 180 mg/dl 2-hOR
2-h
> 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 >30).
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 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% of total calories) are distributed, as needed, as snacks.

41. Monitoring BG Atleast 4 times Pre vs postprandial monitoring
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 < 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)
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
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) > 95 or PP > 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 Glibenclamide
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 Acarbose Thiazolidinediones and GLP-1
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 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: 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: 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
5–15 % 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 <40 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
6m , 15m and 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 < 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 < 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 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