GESTATIONAL DIABETES MELLITUS -GESTATIONAL DIABETES MELLITUS - CURRENT CONCEPTS CURRENT CONCEPTS

Dr.Vivek Sundaram.MD.DNB.MRCP(UK)Consultant – Internal Medicine,Diabetes & Critical Care

Sundaram Hospital,Trichy.

Watching TV for 2 hours/day increases Risk of diabetes by 20%....JAMA,June 2011

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”

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.

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.

Diabetes and Pregnancy – Why it is relevant?

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.

GDM………

GDM IGT2%

Agarwal S, Gupta AN. Gestational Diabetes. J Assoc Physicians India 1982;30:203

2% Ramachandran A, et .al., High

prevalence of diabetes in an urban population in south India. BMJ 1988;3; 297(6648):587-90

1980s

7.6%Narendra J, Munichoodappa C, et al, Prevalence of glucose intolerance during pregnancy. Int J Diab Dev Countries 1991;11:2-4

8.2%Ramachandran A, Snehalatha c, Dharmaraj D, Viswanathan M. Prevalence of glucose intolerance in Asian Indians. Diabetes Care 1992; 15:1348-55

1990s

16.6%V Seshiah, V Balaji, Madhuri S Balaji, CB Sanjeevi, A. Green. Gestational Diabetes Mellitus in India. J Assoc Physicians India 2004;52:707

14.5%Ramachandran A, Snehalatha C, Kapur A, Vijay V, Mohan V,Das AK, Rao PV, Yajnik CS, Prasanna Kumar KM, Nair JD.For the Diabetes Epidemiology Study Group in India (DESI).Diabetologia 2001;44:1094-1101.

2000s

GDM prevalence linked to background IGT rates

FREINKEL HYPOTHESIS

Uterine After Birth

Maternal

DM

placenta

A.AFatCHO

At Birth

Macrosomia

Hypoglycemia

Fetus

Amniotic Fluid Insulin

Obesity

Metabolic syndrome

CVD

IGT/DM

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.

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”

GDM –POSTPRANDIAL HYPERGLYCEMIA IS MORE RELEVANT

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

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?

Who & When to screen?

First booking – Differentiates pre GDM from GDM

24-28 weeks [ Repeat - GTT]

32 -34 weeks [ Repeat -GTT]

UNIVERSAL

How to screen?

One Step Approach – Validated in the indian population

2 hrs value >140 mg/dl with 75g oral glucose -GDM

( irrespective of the time last meal was consumed)

Definitive testDefinitive test: 75gm 2 hour OGTT ( ADA Criteria): 75gm 2 hour OGTT ( ADA Criteria)

If negative rescreen at 24 weeks /32 weeksIf negative rescreen at 24 weeks /32 weeks

If positive proceed to treatmentIf positive proceed to treatment

Gestational DM-Revised ADA criteria (2011)

75 g OGTT at 24-28 wks of gestation

Fasting > 92 mg/dl

1 hr >180 mg/dl

2 hr > 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

Occurrence of birth weight of new born > 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

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 < 0.05])

Balaji V, Balaji MS, Seshiah V, Mukundan S, Datta M.Diabetes Res Clin Pract. 2006 Aug;73(2):223-4.

Abnormal : FPG > 90 & PPG > 120 mg/dl

19

TARGET BLOOD GLUCOSE LEVELS

Oded Langer. Maternal glycemic criteria for insulin therapy in GDM. Diabetes care, vol 21 (2), August 1998. B91-98.

Fasting PG

80 mg %

90 mg %

PPG

110 mg %

120 mg %

Mean PG level

95 mg %

105 mg %

V. Seshiah, AK Das, Balaji V, Shashank Joshi, MN Parikh, Sunil Gupta for DIPSI. GDM- Guidelines. JAPI vol 54, 2006, 622-28

Balaji V, Balaji MS, Seshiah V, Mukundan S, Datta M.Diabetes Res Clin Pract. 2006 Aug;73(2):223-4.

Birth weight between 2.5 and 3.5 KgVinod 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.

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 born2020

Fetal Morbidity

Maternal Morbidity

• Hypertension/Preeclampsia and Eclampsia

• Cesarean delivery; Pre term labour

• Polyhydramnios – fluid > 2000 ml

• Post-partum uterine atony

• Abruptio placenta

• 40-60% risk of DM (screen 6 wk/6 mths after delivery)

2222

AimAim To maintain plasma glucose To maintain plasma glucose

values as to that of non values as to that of non diabetic pregnancydiabetic pregnancy

MANAGEMENT

How to treat?

Medical nutrition therapy (MNT)

Exercise

Insulin

MNT

2 wk trial – if uncontrolled switch over to insulin

30 kcal/kg/day for 60 kg

BMI>30- 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

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.

Insulin therapy

Safe ,Effective, time tested

Human Insulin preferred

Short acting analogues – good option

May need short term hospitalization

Monitoring fasting, premeals & post meal

CHARLES BEST –FRED BANTINGCHARLES BEST –FRED BANTING

Fonseca V. Curr Med Res Opin 2003;19:635–641.

Insulin secretion defect in diabetes

-30 0 30 60 90 120

Normal

2e fase

Time (min)

120

100

80

60

40

20

0

1ste fase(acute afgifte)

Plasma-immunoreactiveInsulin (µU/mL)

-30 0 30 60 90 120

Diabetes

120

100

80

60

40

20

0

Time (min)

Plasma-immunoreactiveInsulin (µU/mL)

30

• Normal insulin physiology is matched by multiple insulin injections

Insulin therapy should closely mimic normal insulin physiology Basal needs: Intermediate-/long-acting insulins (NPH, ILPS, detemir, glargine)

Bolus needs: Rapid-/short-acting insulins given with meals (lispro, aspart, glulisine, human regular insulin)

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.

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

So, Why Modern Insulins ?

Dissociation of Insulins

Regular Human Insulin

10-3 M 10-3 M 10-5 M 10-8 M

Formulation

Capillary membraneAnalogs

10-3 M 10-3 M 10-3 M

FormulationTransient

Peak time1 hr

Peak time2-4 hr

Presentation titleSlide no 34

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

Presentation titleSlide no

35Date

• Physiological insulin profile:basal componentmeal-related peaks

• Regular insulin fails to match normal insulin peak

Fails to match the physiology

Presentation titleSlide no

36Date

• Physiological insulin profile: basal component

meal-related peaks

• Mixtard fails to re-create the physiological insulin profile

Period of unwanted hyperglycemia Period of unwanted

hypoglycemia

Presentation titleSlide no 37 Date

30%

Protamine-crystallisedinsulin

Soluble insulin analogue

Premixed is a suspension of:

30% Solublehuman insulin

NPH

INSULIN TACTICS

Twice-daily Split-mixed Regimens

RegularNPH

B SL HS

Insu

lin E

ffect

B

6-23

INSULIN TACTICS

Multiple Daily Injections (MDI):NPH + Mealtime Lispro

NPH at AM and HS + Lispro AC NPH at HS + Lispro AC

Insu

lin E

ffect

B SL HS B

Insu

lin E

ffect

B SL HS B

LisproNPH

LisproNPH

6-29

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 30:70 mix

• Give 1/3 before supper = 15 u of 30:70 mix

• Increase total dose by 2-4 units based on BG

4040

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

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):2003-2015May 8, 2008

Monitoring HbA1c LevelsMonitoring 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.

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

RICHARD S. HOLLIS PRESIDENT ACOG

Remember how fortunate we are to be included in the lives of our patients at the

most precious times of their lives

ILLNESSWELLNESS

THANK YOU