GESTATIONAL DIABETES MELLITUS - CURRENT CONCEPTS

1
GESTATIONAL DIABETES MELLITUS - CURRENT CONCEPTS

• Dr.Vivek Sundaram.MD.DNB.MRCP(UK)
• Consultant Internal Medicine,Diabetes
  Critical Care
• Sundaram Hospital,Trichy.

2
Watching TV for 2 hours/day increases Risk of
diabetes by 20....JAMA,June 2011
3
ARETAEUS(200 A.D.) .wonderful affliction with
melting down of flesh and limbs into
urine..patient never stops making water
..illness is chronic but the patient
shortlived
4
Definition

• Gestational Diabetes Mellitus (GDM) is defined as
  -carbohydrate intolerance with recognition or
  onset during pregnancy, irrespective of the
  treatment with diet or insulin.
• The importance of GDM is that two generations are
  at risk of developing diabetes in the future.

5

• The maternal metabolic adaptation is to maintain
  the mean FBG of 74.5 11 mg/dl and the PPG peak
  of 108.7 16.9mg/dl.1
• Compensatory hyperinsulinaemia due to
  insulin resistance.
• Failure of beta cells secretion to overcome the
  insulin resistance leads to GDM.

6
Diabetes and Pregnancy Why it is relevant?
7
GDM

• Pregnancy diabetogenic condition (metabolic
  stress test)
• Unmasks a compensated metabolic abnormality
• A direct consequence of the altered maternal
  metabolism
• stemming from the changing hormonal milieu.

8
GDM prevalence linked to background IGT rates
9
FREINKEL HYPOTHESIS
Uterine
After Birth
At Birth
placenta
Macrosomia
Obesity
Hypoglycemia
Maternal DM
Metabolic syndrome
IGT/DM
Amniotic Fluid Insulin
Fetus
A.A Fat CHO
CVD
10
Pathophysiology

• Human Placental Lactogen (HPL)
• Produced by syncytiotrophoblasts of placenta.
• Acts to promote lipolysis ? increased Free fatty
  acids contributing to tissue insulin resistance.
• Estrogen and Progesterone
• Interfere with insulin-glucose relationship.
• Insulinase
• Placental product that may play a minor role.

11
Pathophysiology

• Normal pregnancy
• - Mild fasting hypoglycemia increased lipolysis
  and FFAs become the main fuel substrate for the
  mother ( Mediated by human placental growth
  harmone)-accelerated starvation
• - Postprandial hyperglycemia insulin resistance
  aids glucose transfer to the fetus facilitated
  anabolism

12
GDM POSTPRANDIAL HYPERGLYCEMIA IS MORE RELEVANT
13
Risk Factors

• Age ? 35 years
• Obesity (BMI ? 30 kg/m2)
• Family history
• Previous delivery of a macrosomic infant
• Member of a high-risk population
• Polycystic ovarian syndrome
• Previous abnormal glucose tolerance

INDIAN - ETHNICITY
14
GDM dilemmas

• Early or late sreening?
• WHO or ADA criteria
• One step or twostep?
• 75 or 100 gm?
• 1 hour or 2 hour?

• To treat or not ?
• Insulin or pills?
• Early or late delivery?
• C section or normal?
• Breast feed or not?

15
Who When to screen?
UNIVERSAL

• First booking Differentiates pre GDM from GDM
• 24-28 weeks Repeat - GTT
• 32 -34 weeks Repeat -GTT

16
How to screen?

• One Step Approach Validated in the indian
  population
• 2 hrs value gt140 mg/dl with 75g oral glucose
  -GDM
• ( irrespective of the time last meal was
  consumed)
• Definitive test 75gm 2 hour OGTT ( ADA
  Criteria)
• If negative rescreen at 24 weeks /32 weeks
• If positive proceed to treatment

17
Gestational DM-Revised ADA criteria (2011)75 g
OGTT at 24-28 wks of gestation
Fasting gt 92 mg/dl
1 hr gt180 mg/dl
2 hr gt 153 mg/dl
_
_
_
ANY 1 ABNORMAL VALUE - GDM
100 g OGTT O,I,2,3 hr values . 95,180,155,140
2 abnormal values
18
Abnormal Plasma Glucose during Pregnancy
The occurrence of macrosomia was continuum as the
2 hr plasma glucose increased from 120 mg/dl
(adjusted odds ratio 3.02 95 CI 1.30 7.00,
P lt 0.05)
Balaji V, Balaji MS, Seshiah V, Mukundan S, Datta
M.Diabetes Res Clin Pract. 2006 Aug73(2)223-4.

• Occurrence of birth weight of new born gt 90th
  percentile was continuum as FPG increased from 80
  mg/dl and was significant above 90 mg/dl
  (adjusted odds ratio 2.08 95 CI 1.24 3.48,
  P 0.005)

V Seshiah, V Balaji, Madhuri S Balaji, A
Paneerselvam. Abnormal Fasting Plasma Glucose
during Pregnancy. Diabetes Care vol 31 (12) e92,
December 2008
Abnormal FPG gt 90 PPG gt 120 mg/dl
19
TARGET BLOOD GLUCOSE LEVELS
Fasting PG
80 mg 90 mg
PPG
110 mg 120 mg
Mean PG level
95 mg 105 mg
Balaji V, Balaji MS, Seshiah V, Mukundan S, Datta
M.Diabetes Res Clin Pract. 2006 Aug73(2)223-4.
V. Seshiah, AK Das, Balaji V, Shashank Joshi, MN
Parikh, Sunil Gupta for DIPSI. GDM- Guidelines.
JAPI vol 54, 2006, 622-28
Oded Langer. Maternal glycemic criteria for
insulin therapy in GDM. Diabetes care, vol 21
(2), August 1998. B91-98.
Birth weight between
2.5 and 3.5 Kg
Vinod K Paul, Ashok K Deorari, Meharban Singh.
Management of Low Birth Weight Babies. In IAP
Textbook of Pediatrics. 2nd ed. A. Parthasarathy,
editor. Jaypee publications, 2002, p60.
20
GDM Fetal Morbidity

• Macrosomia of the baby
• CPD Shoulder Dystocia
• Intrapartum Trauma Feto-maternal
• Neonatal Hypoglycemia
• Neonatal Hypocalcemia
• Neonatal Hyperbilirubinemia
• Respiratory Distress Syndrome (RDS)
• Polycythemia (secondary) in the new born

21
Fetal Morbidity
22
Maternal Morbidity

• Hypertension/Preeclampsia and Eclampsia
• Cesarean delivery Pre term labour
• Polyhydramnios fluid gt 2000 ml
• Post-partum uterine atony
• Abruptio placenta
• 40-60 risk of DM (screen 6 wk/6 mths after
  delivery)

23
Aim To maintain plasma glucose values as to
that of non diabetic pregnancy
MANAGEMENT
24
How to treat?

• Medical nutrition therapy (MNT)
• Exercise
• Insulin

25

• MNT
• 2 wk trial if uncontrolled switch over to
  insulin
• 30 kcal/kg/day for 60 kg
• BMIgt30- 25kcal/kg/day
• 300 extra calories for 2 3 trimester
• 3 meals 3 snacks - avoid hypoglycemia
• 40 50 of calories as CHO,25 each as fat and
  protein

26
Exercise

• Women with GDM often need regular, moderate
  physical activity to help control their blood
  sugar levels by allowing insulin to work better.
• Examples include
• Walking
• Prenatal aerobics classes
• Swimming

Keep in mind that it may take 2 to 4 weeks before
physical activity has an effect on blood sugar
levels.
27
Insulin therapy

• Safe ,Effective, time tested
• Human Insulin preferred
• Short acting analogues good option
• May need short term hospitalization
• Monitoring fasting, premeals post meal

28
(No Transcript)
29
Insulin secretion defect in diabetes
Normal
Diabetes
Plasma-immunoreactive Insulin (µU/mL)
Plasma-immunoreactive Insulin (µU/mL)
1ste fase (acute afgifte)
120
120
100
100
80
80
60
60
40
40
2e fase
20
20
0
0
-30 0 30 60 90 120
-30 0 30 60 90 120
Time (min)
Time (min)
Fonseca V. Curr Med Res Opin 200319635641.
30
Insulin Therapy-
Physician Expectations
Insulin therapy should closely
mimic normal insulin physiology
Meal
Meal
Meal
Expected insulin changes during the day for
individuals without diabetes Insulin effect
images are theoretical representations and are
not derived from clinical trial data.

• Normal insulin physiology is matched by multiple
  insulin injections

31
Comparison of Human insulins/Analogs
Insulin Onset
Peak Duration
Short acting Regular
30-60 min 2-4 h 4-6 h Lispro/aspart
5-15 min 1-2 h
3-4 h Glulisine Intermediate
acting NPH 1-4 h 4-8 h 10-20
h Long acting Glargine 1-2 h
Flat 24 h Detemir
1-4 Flat
12-20
32

• So, Why Modern Insulins ?

33
Dissociation of Insulins
Regular Human Insulin
10-3 M
10-3 M
10-5 M
10-8 M
Û
Û
Û
Formulation
Capillary membrane
Analogs
10-3 M
10-3 M
10-3 M
Û
Û
Formulation
Transient
34
Limitations of conventional soluble human insulin

• Inability of s.c. injected soluble insulin to
  mimic the physiological pattern
• Delayed onset of action (30-60 min after
  injection) i.e. should be injected 30-60 min
  prior to a meal
• Prolonged duration of action (6-8 hrs after
  injection)
• Inadequate insulin when in need
• Insulin when not needed

35
The shortcomings of conventional insulin
(regular)

• Physiological insulin profile
• basal component
• meal-related peaks

36
Shortcomings of human insulin

• Physiological insulin
• profile basal component
• meal-related peaks

Period of unwanted hyperglycemia
Period of unwanted hypoglycemia
37
What is premixed insulin?
Premixed is a suspension of
30
Soluble insulin analogue
30
Soluble human insulin
Protamine-crystallised insulin
NPH
38
INSULIN TACTICS Twice-daily Split-mixed Regimens
Regular
NPH
Insulin Effect
B
S
L
HS
B
6-23
39
INSULIN TACTICS Multiple Daily Injections
(MDI)NPH Mealtime Lispro
NPH at AM and HS Lispro AC
NPH at HS Lispro AC
6-29
40
Insulin Regimen

• If MNT fails after 2 wks of trial initiate
  Insulin
• 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 3070 mix
• Give 1/3 before supper 15 u of 3070 mix
• Increase total dose by 2-4 units based on BG

41
Oral agents -GDM

• Glibenclamide ( Currently not recommended)
• Metformin Select group ( pre GDM/PCOS)

ADVANTAGES Easy to take Need far less
education Affordable No social stigma
Not endorsed by any formal recommendations apart
from NICE Guidelines
42
(No Transcript)
43
Original Article Metformin versus Insulin for
the Treatment of Gestational Diabetes
Janet A. Rowan, M.B., Ch.B., William M. Hague,
M.D., Wanzhen Gao, Ph.D., Malcolm R. Battin,
M.B., Ch.B., M. Peter Moore, M.B., Ch.B., for the
MiG Trial Investigators
N E J M.358(19)2003-2015 May 8, 2008
44
Monitoring HbA1c Levels

• HbA1c in early pregnancy - differentiates
  between a pre gestational diabetic and GDM. If
  the HbA1c level is more than 6, she is likely to
  be a pre GDM.
• HbA1c is useful in monitoring the glucose
  control during pregnancy, but not for the day to
  day management. Estimation of fructosamine during
  pregnancy is less frequently used.

45
Conclusions

• Universal screening ideal for our women
• 2 hour 75 gm screening is cost effective
• 2 hour 75 gm GTT ( Definitive test)
• Diet and exercise provides good control in many
• Insulin analogues are safe and very effective
• Oral agents are an alternative in select
  situations
• Postpartum follow-up is an integral part of GDM
  management

46
Remember how fortunate we are to be included in
the lives of our patients at the most precious
times of their lives

• Richard S. Hollis President ACOG

47
ILLNESS WELLNESS
48
THANK YOU