gestational diabetes

Gestational DiabetesGestational DiabetesYannis DimitropoulosYannis Dimitropoulos

ST3 in Diabetes and EndocrinologyST3 in Diabetes and EndocrinologyTorbay HospitalTorbay Hospital

Buckfast Abbey Diabetes and Endocrinology Training DayBuckfast Abbey Diabetes and Endocrinology Training Day

07/05/201007/05/2010

What we will CoverWhat we will Cover

Definition and Aetiology of Gestational Definition and Aetiology of Gestational Diabetes Diabetes

Importance of diagnosis and treatment of Importance of diagnosis and treatment of Diabetes in pregnancyDiabetes in pregnancy

Aims and modalities of treatment Aims and modalities of treatment according to best available evidenceaccording to best available evidence

GESTATIONAL DIABETES(GDM)GESTATIONAL DIABETES(GDM)

A carbohydrate intolerance of variable A carbohydrate intolerance of variable severity with its onset/first recognition in severity with its onset/first recognition in pregnancy pregnancy

This includes GDM that reverts to normal This includes GDM that reverts to normal carbohydrate tolerance post-partum, but carbohydrate tolerance post-partum, but also all undiagnosed DM1, DM2 and rare also all undiagnosed DM1, DM2 and rare monogenic Diabetes first detected during monogenic Diabetes first detected during pregnancypregnancy

Why does Gestational Diabetes Why does Gestational Diabetes Mellitus happen?Mellitus happen?

Increasing prevalence of obesity in the Increasing prevalence of obesity in the population of women of childbearing age population of women of childbearing age

augments insulin resistance. augments insulin resistance.

Increasing maternal age also portends Increasing maternal age also portends increased insulin resistanceincreased insulin resistance

Insulin resistance increases further Insulin resistance increases further during pregnancyduring pregnancy

0

20

40

60

80

100

Age

ß-c

ell

fun

ctio

n (

%)

–10 –8 –6 –4 –2 0 2 4 6–12

Deterioration of Deterioration of ββ cell function cell function and insulin and insulin resistance in Type 2 diabetesresistance in Type 2 diabetes

30 40 50 60 70

0

20

40

60

80

100

Age

ß-c

ell

fun

ctio

n (

%)

–10 –8 –6 –4 –2 0 2 4 6–12

Deterioration of Deterioration of ββ cell function cell function and insulin and insulin resistance in resistance in Gestational DMGestational DM

30 40 50 60 70

Why is it important to treat Why is it important to treat Gestational Diabetes?Gestational Diabetes?

Pedersen Hypothesis (1954)Pedersen Hypothesis (1954)

Maternal hyperglycaemia leads to foetal Maternal hyperglycaemia leads to foetal hyperglycaemia which evokes an hyperglycaemia which evokes an exaggerated response to Insulin which exaggerated response to Insulin which causes increased neonatal fat deposition causes increased neonatal fat deposition and abdominal girth with increased birth and abdominal girth with increased birth weight.weight.

The above was further supported by The above was further supported by recent studies (HAPO study associations recent studies (HAPO study associations with neonatal anthropometrics, 2009)with neonatal anthropometrics, 2009)

Australian Carbohydrate Australian Carbohydrate Intolerance Study in Pregnant Intolerance Study in Pregnant

Women (ACHOIS) 2005Women (ACHOIS) 2005 Randomized double-blind intervention trial: 1000 women Randomized double-blind intervention trial: 1000 women

with GDM randomly assigned to ‘Intensive’ versus with GDM randomly assigned to ‘Intensive’ versus ‘Routine’ care‘Routine’ care

Intensive care:Intensive care: Diet and monitoring (2 weeks)Diet and monitoring (2 weeks) Treat with insulin if 2Treat with insulin if 2 XX FPG >5.5 and/or 2 FPG >5.5 and/or 2 XX 2-hr post- 2-hr post-

prandial glucoses >7 (>8 if after 35/40)prandial glucoses >7 (>8 if after 35/40) All treated with multiple Insulin injectionsAll treated with multiple Insulin injections

Significant reduction in the rate of perinatal complications Significant reduction in the rate of perinatal complications in the intervention group (1%) compared to the routine care in the intervention group (1%) compared to the routine care group (4%). group (4%).

ACHOIS ResultsACHOIS Results

OutcomeOutcome Intervention Intervention Routine GroupRoutine Group

InfantsInfants NumberNumber Number Number

Total numberTotal number 506506 524524

Birth weightBirth weight 3335g3335g 3482g3482g

Macrosomia Macrosomia (>4kg)(>4kg)

49 49 (10%)(10%) 110 110 (21%)(21%)

Death Death (Neonatal/Stillbirth)(Neonatal/Stillbirth)

0 0 5 5

StillbirthStillbirth 00 3 3

Shoulder dystociaShoulder dystocia 7 7 16 16

Bone fracture Bone fracture 00 1 1

Nerve palsyNerve palsy 00 3 3

Jaundice Jaundice 44 44 48 48

Hyperglycaemia and Adverse Hyperglycaemia and Adverse Pregnancy Outcomes (HAPO) 2008Pregnancy Outcomes (HAPO) 2008

Observational multi -centre study (25.505 patients with GDM) showing Observational multi -centre study (25.505 patients with GDM) showing continuous graded associationscontinuous graded associations of maternal blood glucose levels of maternal blood glucose levels below those diagnostic of Diabetes with:below those diagnostic of Diabetes with:

Primary outcomes:Primary outcomes: -increased birth weight (strong association)-increased birth weight (strong association) -increased cord-blood serum C-peptide levels (strong association)-increased cord-blood serum C-peptide levels (strong association) -C-section (weaker association)-C-section (weaker association) -Neonatal hypoglycaemia (weaker association)-Neonatal hypoglycaemia (weaker association)Secondary outcomes:Secondary outcomes: -Premature (<37/40) delivery, -Premature (<37/40) delivery, -Shoulder dystocia/birth trauma, -Shoulder dystocia/birth trauma, -Admission to NICU-Admission to NICU -Preeclampsia and Hyperbilirubinaemia-Preeclampsia and Hyperbilirubinaemia

Hyperglycaemia and Adverse Hyperglycaemia and Adverse Pregnancy Outcomes (HAPO) 2008Pregnancy Outcomes (HAPO) 2008

There were There were no obvious glucose no obvious glucose thresholds at which risks increased.thresholds at which risks increased.

The results were applicable to all centres The results were applicable to all centres and were independent of other risk factors.and were independent of other risk factors.

International Association of Diabetes International Association of Diabetes and Pregnancy Study Groups and Pregnancy Study Groups

(IADPSG) Consensus panel (2008)(IADPSG) Consensus panel (2008) The panel recommends testing of FBG, HbA1c or RPG on The panel recommends testing of FBG, HbA1c or RPG on all high-all high-

risk pregnant women.risk pregnant women. Diagnostic of overt Diabetes:Diagnostic of overt Diabetes: FPG FPG ≥≥7.0, HbA1c 7.0, HbA1c ≥≥6.5%, RPG 6.5%, RPG ≥≥11.1 11.1 (Treat as established pregnant diabetic) (Treat as established pregnant diabetic) Diagnostic of GDM:Diagnostic of GDM: FPG FPG ≥≥5.1 but <7.15.1 but <7.1

If results not diagnostic of Diabetes (FPG < 5.1) then 75g OGTT at If results not diagnostic of Diabetes (FPG < 5.1) then 75g OGTT at weeks 24-28 for weeks 24-28 for all all pregnant women at riskpregnant women at risk

Overt Diabetes ifOvert Diabetes if FPG FPG ≥≥7.07.0 GDM if FPG GDM if FPG ≥≥ 5.1 5.1 1hr PG 1hr PG ≥≥10 10 2hr PG 2hr PG ≥≥8.58.5

NICE Guidelines 2008NICE Guidelines 2008

CEMACH: adverse outcomes in pregnant CEMACH: adverse outcomes in pregnant women with type 1 and type 2 diabetes, women with type 1 and type 2 diabetes,

2002/3 and 20072002/3 and 2007

NICE -Risks of Gestational NICE -Risks of Gestational Diabetes in PregnancyDiabetes in Pregnancy

Foetal macrosomiaFoetal macrosomia Birth trauma (to mother and baby)Birth trauma (to mother and baby) IOL or caesarean sectionIOL or caesarean section Transient neonatal morbidityTransient neonatal morbidity Neonatal hypoglycaemiaNeonatal hypoglycaemia Perinatal deathPerinatal death Obesity and/or Diabetes developing later on in Obesity and/or Diabetes developing later on in

baby’s lifebaby’s life increased risk of the mother developing GDM increased risk of the mother developing GDM

with following pregnancies and Diabetes later in with following pregnancies and Diabetes later in lifelife

NICE -Risk Factors for Screening NICE -Risk Factors for Screening for GDMfor GDM

BMI> 30kg/mBMI> 30kg/m²²Previous macrosomic baby 4.5kg or abovePrevious macrosomic baby 4.5kg or aboveFoetal abdominal circumference Foetal abdominal circumference >97>97thth centile on centile on

USSUSSPrevious Gestational DiabetesPrevious Gestational DiabetesPolyhydramniosPolyhydramniosHistory of PCOSHistory of PCOSFamily history of Diabetes (first degree)Family history of Diabetes (first degree)Family origin with a high prevalence of Diabetes Family origin with a high prevalence of Diabetes (South Asian, Afro-Caribbean, Middle Eastern, Chinese)(South Asian, Afro-Caribbean, Middle Eastern, Chinese)

The Torbay Hospital Antenatal The Torbay Hospital Antenatal Diabetes Clinic referral processDiabetes Clinic referral process

If previously diagnosed with GDM, Obstetric If previously diagnosed with GDM, Obstetric Clinic review with dating scan (12/40) for OGTT Clinic review with dating scan (12/40) for OGTT at earliest opportunity or proceed directly to CBS at earliest opportunity or proceed directly to CBS monitoring if previous Insulin-treated GDM.monitoring if previous Insulin-treated GDM.

For all others with risk factors OGTT at 28/40For all others with risk factors OGTT at 28/40

Refer to Diabetes ANC if:Refer to Diabetes ANC if: Fasting blood glucose >5.5 Fasting blood glucose >5.5 mmol/lmmol/l

Low-risk GDM if 2hr glucose 7.8-8.5Low-risk GDM if 2hr glucose 7.8-8.5mmol/lmmol/l

High-risk GDM if 2hr glucose >8.5 High-risk GDM if 2hr glucose >8.5 mmol/lmmol/l

Low vs. High Risk GDM Low vs. High Risk GDM managementmanagement

Low Risk: Low Risk: If macrosomia or polyhydramnios on USS, refer If macrosomia or polyhydramnios on USS, refer

to Diabetes ANC directly.to Diabetes ANC directly. If USS normal, review by midwife for diet and If USS normal, review by midwife for diet and

lifestyle advice. CBS monitoring for 1 week and lifestyle advice. CBS monitoring for 1 week and review by Diabetes Specialist Midwife. If CBS review by Diabetes Specialist Midwife. If CBS <5.5 fasting and <7.0 post-prandial, for repeat 1 <5.5 fasting and <7.0 post-prandial, for repeat 1 week CBS monitoring at 33/40 and repeat week CBS monitoring at 33/40 and repeat growth scan at 36/40.growth scan at 36/40.

The Torbay Hospital Diabetes The Torbay Hospital Diabetes Antenatal ClinicAntenatal Clinic

Multi –disciplinary:Multi –disciplinary: Diabetes in Pregnancy Specialist NurseDiabetes in Pregnancy Specialist Nurse Specialist Diabetes DieticianSpecialist Diabetes Dietician Consultant Diabetologist (and/or SpR)Consultant Diabetologist (and/or SpR) Diabetes Specialist Midwife Diabetes Specialist Midwife


CBS values and patterns are reviewed in association with dietary, CBS values and patterns are reviewed in association with dietary, especially carbohydrate intake. especially carbohydrate intake.

Further patient education regarding the significance of monitoring Further patient education regarding the significance of monitoring blood sugars in pregnancy and the effect of dietary intake on CBS blood sugars in pregnancy and the effect of dietary intake on CBS readings.readings.

In some cases, a further week of monitoring with tight dietary controlIn some cases, a further week of monitoring with tight dietary control Progression to Insulin treatment if CBS still high. Progression to Insulin treatment if CBS still high. Patients may need a full basal Bolus type regime with TDS short-Patients may need a full basal Bolus type regime with TDS short-

acting Novorapid and Insulatard nocte ab initio or insulin at certain acting Novorapid and Insulatard nocte ab initio or insulin at certain times of the day to begin with. Insulin requirements gradually times of the day to begin with. Insulin requirements gradually increase up to week 37/40, then decline.increase up to week 37/40, then decline.

For selected cases, Metformin or Glibenclamide are used.For selected cases, Metformin or Glibenclamide are used. The aims of the treatment are:The aims of the treatment are: fasting values <5.5mmol/l fasting values <5.5mmol/l post-meal values <7.0mmol/l post-meal values <7.0mmol/l


Intra-partum management plan is outlined in the multi-disciplinary Intra-partum management plan is outlined in the multi-disciplinary “Diabetes in Pregnancy” notes by week 32/40. “Diabetes in Pregnancy” notes by week 32/40.

For all DM1, DM2 and GDM patients on Insulin, Sliding-scale Insulin For all DM1, DM2 and GDM patients on Insulin, Sliding-scale Insulin is usually started whilst in established labour and stopped post-is usually started whilst in established labour and stopped post-vaginal delivery. vaginal delivery.

Sliding-scale Insulin may be continued for a short period of time in Sliding-scale Insulin may be continued for a short period of time in cases of C-Section.cases of C-Section.

Post-natal issuesPost-natal issues Advice regarding GDM risk in future pregnancies, the importance of Advice regarding GDM risk in future pregnancies, the importance of

weight-control and screening prior to future planned pregnancies. weight-control and screening prior to future planned pregnancies. Post-partum 6/52 FPG Post-partum 6/52 FPG

REFERENCESREFERENCES

ACHOIS Trial NEJM June 2005 Vol. 352 no 24, pp. 2477-2486ACHOIS Trial NEJM June 2005 Vol. 352 no 24, pp. 2477-2486 HAPO Study NEJM May 2008 Vol. 358, no 19, pp. 1991-2003HAPO Study NEJM May 2008 Vol. 358, no 19, pp. 1991-2003 HAPO study associations with neonatal anthropometrics 2009HAPO study associations with neonatal anthropometrics 2009 CEMACH: adverse outcomes in pregnant women with type 1 and CEMACH: adverse outcomes in pregnant women with type 1 and

type 2 diabetes, 2002/3 and 2007type 2 diabetes, 2002/3 and 2007 IADPSG Consensus Panel statement 2008IADPSG Consensus Panel statement 2008 NICE guideline: Diabetes in Pregnancy March 2008NICE guideline: Diabetes in Pregnancy March 2008 South Devon Healthcare NHS Foundation Trust clinical guideline South Devon Healthcare NHS Foundation Trust clinical guideline

0485: Diabetes in Pregnancy (reviewed 2009)0485: Diabetes in Pregnancy (reviewed 2009) Effects of treatment in women with GDM: systematic review and Effects of treatment in women with GDM: systematic review and

meta-analysis BMJ April 2010 vol. 340: p. 796meta-analysis BMJ April 2010 vol. 340: p. 796 Medical Management of Diabetes in Pregnancy. Rob Dyer, Kath Medical Management of Diabetes in Pregnancy. Rob Dyer, Kath

Williams, Jane Hogg and Sarah Thorne Torbay 2010Williams, Jane Hogg and Sarah Thorne Torbay 2010

Thank you!Thank you!

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