1. Gestational Diabetes Mellitus
Dr. R V S N Sarma., M.D., M.Sc., (Canada)
Consultant Physician & Chest Specialist
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2. Gestational Diabetes Mellitus
Is it physiological?
Is it a disease?
Should we screen for gdm?
Does it require treatment?
Recent RCTs settled the issues
Crowther et al. NEJM 2005;352

3. Glucose Intolerance in Pregnancy
Prevalence
of GDM 3 to 18 %

4. GDM - Definition Distinguish GDM from Pre-gestational DM
Abnormal Glucose Tolerance
Onset (begins) with pregnancy or
Detected first time during pregnancy
No h/o of pre pregnancy DM or IGT
Hb A 1 c is usually < 7.5 in GDM
In DM + Pregnancy it is > 7.5
GDM is a forerunner of T2DM

5. Pathogenesis of GDM Pregnancy is Diabetogenic condition
A Wonderful Metabolic Stress Test
Placental Diabetogenic Hormones
Progesterone, Cortisol, GH
Human Placental Lactogen (HPL), Prolactin
Insulin Resistance (IR), ↑  cell stimulation
Reduced Insulin Sensitivity up to 80%
Impaired 1st phase insulin, Hyperinsulinemia
Islet cell auto antibodies (2 to 25% cases)
Glucokinase mutation in 5% of cases

6. Fundamental Defect in GDM
The hormones of pregnancy cause IR
They also cause direct hyperglycemia
But, the basic defect is
The maternal pancreatic  cells are unable to compensate for this increased demand

7. Normal Glucose Tolerance

8. Abnormal GT in GDM

9. Risk Stratification for GDM
High Risk Group (Indians mostly)
BMI  30; PCOD; Age > 35 years
F h/o DM; Ethnic predisposition; Acanthosis
Previous h/o GDM, IGT, Macrosomic baby
Low Risk Group
Age < 25, BMI < 23, No F h/o DM or IGT
No bad obstetric history; No ↑ risk ethnicity
Intermediate Risk Group
Not falling in the above two classes
Adopted from ADA guidelines

10. Whom to Screen for GDM ? Low Risk Group Intermediate Risk Group
No screening required for GDM
Intermediate Risk Group
Screen around 24–28 weeks of gestation
High Risk Group
As soon as possible after conception
Must - before 24–28 weeks of gestation
Better do a full 3 hr OGTT for GDM
If negative – screening in 2nd & 3rd trimester
Adopted from ADA guidelines

11. Indian Scenario
Since the pregnant mothers without any of the risk factors are so very few in India
Since we boast of being in the DM capitol
We need to screen all pregnant women
And identify early the GDM problem
We have enough tough maternal problems
Let us at least treat a treatable problem

12. GDM – Two Step Screening
Do a Random Glucose Challenge Test (GCT)
50 grams of oral glucose any time of day
1 hour post test for plasma glucose (1 hr PG)
Result > 180 mg% - Dx of GDM confirmed
Result > 140 mg% - Dx of GDM suspected
140 to 180 – We need OGTT (100 g) to confirm
One Step Screening
OGTT – 3 hours after 100 g of oral glucose

13. Glucose Challenge Test (GCT)
< 140
No GDM repeat 24 wk
140 to 180
Need to do OGTT – 3 hr
180+
GDM confirmed

14. Please be specific Do not use the ‘loose’ word ‘Blood Sugar’
Be specific to measure ‘Plasma Glucose’
Always venous sample for OGTT
No capillary blood testing for OGTT
NaF to be added as anticoagulant to blood
Centrifuge to separate plasma immediately
Plasma glucose to be estimated a.s.a.p
Glucometer can be used for monitoring

15. One abnormal Value is enough
OGTT –100g –3 hour Test
Test sample timing
Plasma Glucose value
Fasting (mg%) 95
1 hour (mg%)
180
2 hour (mg%)
155
3 hour (mg%)
140
One abnormal
Value is enough

16. Some Questions When to order for USG ? Scan for anomalies at 20-weeks
Growth scans from weeks
Breast feed or not after delivery ?
Must give breast feeding
This reduces maternal glucose intolerance

17. GDM – Fetal Morbidity Macrosomia of the baby CPD – Shoulder Dystocia
Intrapartum Trauma – Feto-maternal
Congenital Anomalies, HCM
Neonatal Hypoglycemia
Neonatal Hypocalcemia
Neonatal Hyperbilirubinemia
Respiratory Distress Syndrome (RDS)
Polycythemia (secondary) in the new born

18. Macrosomia Birth weight > 4000 g - 90th percentile GA
↑ Intrapartum feto-maternal trauma
Increased need for C- Section
20 – 30% of infants of GDM – Macrosomic
Maternal factors for Macrosomia
Uncontrolled Hyperglycemia
Particularly postprandial hyperglycemia
High BMI of mother
Older maternal age, Multiparity

19. Macrosomic Newborn (4.2kg)

20. Shoulder Dystocia
Erb’s palsy

21. Macrosomia GDM Non DM P value Birth Weight 3512 g 3333 g < 0.05 LGA
40.4%
13.7%
< 0.001
Macrosomia
32.0%
11.0%
< 0.01
In this case-control study, we investigated the effects of GDM on birth weight by comparing the offspring of GDM and normal glucose tolerance mothers. The mean birth weight of the offspring of diabetic mothers was approximately 200 gm heavier than the offspring of normal glucose tolerance mothers. The frequency of being large for their gestational age was also higher in GDM offspring. Macrosomia was approximately 3 times more frequent in the offspring of GDM mothers than that of normal mothers.

22. Neonatal Hypoglycemia
Due to fetal hyperinsulinemia
Neonatal plasma glucose < 30 mg%
Poor glycemic control before delivery
Increases perinatal morbidity
Congenital anomalies – 3 to 8 times more
More if periconception hyperglycemia
Assoc. maternal fasting hyperglycemia

23. Minor Adverse Health Effects
Normal GDM DM P
Birth Wt (g) 3303± ± ±72 <0.01
Macrosomia(%) <0.01
C-S <0.01
Hypoglycemia <0.01
Hypocalcemia <0.01
Hyperbilirubinemia <0.01
Polycythemia <0.01
Cord C-Pep 1.18± ± ±0.22 <0.01
Cord Glu 100± ± ±5.5 <0.01
In this retrospective study, we have compared minor birth outcomes among women who were diagnosed with GDM, DM, and who were normal. Significant differences in all minor birth outcome variables were observed. Dose relationships in birth weight, % macrosomia, cesarian rate, hypoglycemia, hypocalcemia, polycythemia, cord c-peptide and glucose were highest in DM patients and followed by GDM patients, then normal individuals. This epidemiologic study clearly shows adverse health effects of diabetes on perinatal health.

24. Major Adverse Health Effects
Normal DM
CNS % 18.4%
Congenital heart disease 7.5% 21.0%
Respiratory disease 2.9% 7.9%
Intestinal atresia % 2.6%
Anal atresia % 2.6%
Renal & Urinary defect 3.1% 11.8%
Upper limb deficiencies 2.3% 3.9%
Lower limb deficiencies 1.2% 6.6%
Upper + Lower spine 0.1% 6.6%
Caudal digenesis % 5.3%
This slide shows the major adverse health effects in the offspring of normal glucose tolerance mothers verses that of diabetic mothers. As shown, frequency of adverse health effects was significantly greater in the offspring of DM mothers. Some of the health effects such as upper+lower spine and caudal dysgenesis were as large as 66 time more in the offspring of diabetic mothers.

25. Neonatal Complications
DM GDM Normal p-value
T. hypoglycemia(%) <0.01
P. hypoglycemia(%) <0.01
Hypocalcemia(%) <0.01
Hyperbilirubinemia(%) <0.01
Trans tachypnea(%) <0.01
Polycythemia(%) <0.01
RDS(%) <0.01 IUGR(%) <0.05
Neonatal complications were significantly more frequent in both the offspring of DM as well as that of the GDM mothers; when compared to the normal glucose tolerance mother. Moreover, these complications were even greater in the offspring of DM mothers than that of GDM mother. This phenomena might suggest neonatal sensitivity to the mother glucose metabolism during the pregnancy.

26. Congenital Anomalies - DM Control
Maternal HbA1c levels
< 7.2 Nil % %
> %
Critical periods weeks post conception
Need pre-conceptional metabolic care

27. Late effects on the offspring
Increased risk of IGT
Future risk of T2DM
Risk of Obesity

28. Maternal Morbidity Hypertension; Insulin Resistance
Preeclampsia and Eclampsia
Cesarean delivery; Pre term labour
Polyhydramnios – fluid > 2000 ml
Post-partum uterine atony
Abruptio placenta

29. Risk of T2DM after GDM IGT and T2DM after delivery in 40% of GDM
R.R of T2DM for all with GDM is 6 (C.I. 4.1 – 8.8)
Must be counseled for healthy life style
Re-evaluate with 75 g OGTT after 6 wk, 6 months
More risk - if GDM before 24 wks of gestation
High levels of hyperglycemia during pregnancy
If the mother is obese and has +ve family h/o
GDM in previous pregnancies and age > 35 yrs.
High risk ethnic group (like Indians)

30. A Delicate Balance ! Plasma Glucose values in pregnancy
hang on a delicate balance
If the Mean Plasma Glucose (MPG) is
Less than 87 mg% - IUGR of fetus
More than 104 mg% - LGA of fetus
It is imp. to screen for hypothyroidism

31. Women with T2DM T2DM patients must plan their pregnancy
Preconception Hb A1c  7.00; MAU estimate
OADs should be discontinued; Folic acid +
Start on Insulin and titrate for euglycemia
Nutrition and weight gain counseling
ACEi and ARB must be substituted
Screening for retinopathy; nephro (eGFR <90)
Must avoid hypoglycemia and ketosis
SMBG must be trained and started

32. Recommended values for
GDM – Glycemic Targets
Recommended values for
Glycemic Targets
Pre-pregnancy Hb A1c
 7.00 (if possible  6.00)
Pregnancy values
Range
FPG
1 hr PPG
100 – 140
2 hr PPG
90 – 120
Hb A1c
 6.00

33. GDM and MNT Two weeks trial of Medical Nutrition Therapy
Pre-pregnancy BMI is a predictor of the efficacy
If target glycemia is not achieved initiate insulin
MNT – extra 300 calories in 2 and 3rd trimesters
Calories – 30 kcal/kg/day = 1800 kcal for 60 kg
If BMI > 30; then only 25 kcal/kg/day
3 meals and 3 snacks – avoid hypoglycemia
50% of total calories as CHO, 25% protein & fat
Low glycemic, complex CHO, fiber rich foods

34. Diet therapy in GDM Small, frequent meals Avoid eating for two
Avoid fasts and feasts
Avoid health drinks
Eat a bedtime snack

35. Tips for diet management
Small breakfast
Mid morning snack
High protein lunch
Mid afternoon snack
Usual dinner
Bed time snack

36. GDM and Exercise Recumbent bicycle Upper body egometric exercises
Moderate exercises
Mother to palpate for uterine contractions
Walking is the simplest and easiest
Continue pre pregnancy activity
Do not start new vigorous exercise

37. GDM and Insulins In 10 to 15% of GDM, MNT fails –Start on insulin
Good glycemic control – No increased risk
Human Insulins only – Not Analogs
Daily SMBG up to 7 times!
Insulin Glargine (Lantus) – Not to be used at all
Insulin Lispro tested and does not cross placenta
Insulin Aspart not evaluated for safty
CSII may be needed in some cases
Oral drugs not recommended (SU?, Metformin?)

38. Insulin Regimen If MNT fails after 2 - 4 weeks of trial
Initiate Insulin + Continue MNT
Dose: 0.7, 0.8 and 0.9 u/kg – 1, 2 & 3 trim.
Eg. 1st trim – 64 kg = 0.7 x 64 = 45 units
Give 2/3 before BF = 30 units of 30:70 mix
Give 1/3 before supper = 15 u of 50:50 mix
Increase total dose by 2-4 units based on BG
After BG levels stabilize – monitor till term

39. GDM and Delivery Delivery until 40 weeks is not recommended
Delivery before 39th week – assess the pulmonary maturity by phosphatase test on amniocentesis fluid
C - Section may be needed (25 -30%)
Be prepared for the neonatal complications
Assess the mother after delivery for glycemia
May need to continue insulin for a few days
Pre-gestational DM–Insulin (30% less) or OAD

40. Jagad Guru Adi Sankaracharya’s Bhaja Govindam
punarapi jananam punarapi maranam
Once again is the birth, sure follows the death
punarapi jananee jaTarae sayanam |
Yet again, is the slumber in the uterine filth
iha samsaarae bahu dustaarae
he! what to say of this miserable troth
kripayaa paarae paahi muraarae ||
O! lord, save us from this cyclical myth
Jagad Guru Adi Sankaracharya’s Bhaja Govindam

41. Punarapi Garbham Yet another conception
Punarapi Prasavam
Yet another child-birth

42. Punarapi Jananee Once again for the mom
Sisuvau KaTinam
and the babe, the miseries

43. Iha Madhu maehae This Diabetes you see
Bahu Dustarae
Terrible to the core

44. Kripaya Nivaaare Please put an end to this
Nipunarae vidyae
O! Doctor, the expert !

45. Punarapi Jananam