gestational diabetes mellitus€¦ · gestational diabetes mellitus . gdm - who definition...

SpR Study Day

Maternal Medicine

W i t h y b u s h G e n e r a l H o s p i t a l H a v e r f o r d w e s t

2 0 A p r i l 2 0 1 2

M r R i c h a r d H u s i c k a

Gestational Diabetes Mellitus

GDM - WHO definition

carbohydrate intolerance resulting in hyperglycaemia of variable severity with onset or first recognition during pregnancy (whether or not insulin is used and regardless of whether diabetes persists after pregnancy)

World Health Organization and Department of Noncommunicable Disease Surveillance. Definition, diagnosis and classification of diabetes mellitus and its complications. Report of a WHO consultation. Part 1: diagnosis and classification of diabetes mellitus. Geneva: World Health Organization; 1999.

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Incidence of DM in pregnancy

3-6% pregnancies with DM in England & Wales around 65 000 births/year

Pre-existing DM 0.37% (12.5% of DM in pregnancy)

Type 1 - 7.5%

Type 2 - 5%

GDM 3.5% in E&W (87.5% of DM in pregnancy) True GDM

Pre-existing DM (1:1000)

Office for National Statistics. Key Population and Vital Statistics 2005. Local and Health Authority Areas. No. Series VS, No 32. Basingstoke: Palgrave Macmillan; 2007.

CEMACH. Confidential Enquiry into Maternal and Child Health: Pregnancy in Women with Type 1 and Type 2 Diabetes in 2002–03, England, Wales and Northern Ireland. London: CEMACH; 2005.

King H. Epidemiology of glucose intolerance and gestational diabetes in women of childbearing age. Diabetes Care 1998;21(Suppl 2): B9–13.

Department of Health. National Service Framework for Diabetes: Standards. London: Department of Health; 2002.

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Clinical features of GDM

Asymptomatic develops in the 2nd or 3rd trimester

Diagnosed by routine biochemical screening

or after suspicious findings

macrosomia, polyhydramnios, persistent glycosuria, recurrent infections

Rarely diagnosed retrospectively after IUD

birth of macrosomic baby

random plasma glucose or HbA1c

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Impact of GDM on pregnancy

increased perinatal morbidity and mortality same way but to a much lesser degree than pre-existing DM

maternal hyperglycaemia

excess transfer of glucose to the fetus

fetal hyperinsulinaemia

Pedersen J. Weight and length at birth of infants of diabetic mothers. Acta Endocrinologica 1954;16(4):330–42.

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Fetal hyperinsulinaemia

An overgrowth of insulin sensitive tissue adipose tissue – chest, shoulders, abdomen

shoulder dystocia, birth trauma, CS, perinatal death

Neonatal metabolic complications hypoglycaemia, RDS, hypocalcemia

A hypoxaemic state in utero risk of IUD, polycythaemia, hyperbilirubinaemia and renal vein

thrombosis

Pedersen J. Weight and length at birth of infants of diabetic mothers. Acta Endocrinologica 1954;16(4):330–42.

Hod M, Rabinerson D and Peled Y. Gestational diabetes mellitus: Is it a clinical entity? Diabetes Reviews 1995;3(4):602–13.

Freinkel N, Metzger BE. Pregnancy as a tissue culture experience: the critical implications of maternal metabolism for fetal development. In:

Pregnancy, Metabolism, Diabetes and the Fetus. CIBA Foundation Symposium 63 (New Series). London: CIBA Foundation; 1979. p. 3–23.

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What to tell women?

All women healthy diet, optimal body weight, exercise

Women with risk factors explain the nature of GDM and impact on pregnancy

risks

importance of the screening

advantages of having GDM diagnosed

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Screening and diagnosis

Original work by O’Sullivan (1964) 100g oral glucose challenge test

O’Sullivan JB, Mahan CM:Criteria for the oral glucose tolerance test in pregnancy.Diabetes 1964;13:278-285

Key questions: What level of maternal hyperglycemia measurably worsens

pregnancy outcome?

Does intervention improve outcome?

Is such intervention cost effective?

What is the optimum screening and/or diagnostic test?

Coustan DR:Management of gestational diabetes mellitus: A self-fulfilling prophecy? JAMA 1996;275:1199-1200

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National Collaborating Centre for

Women’s and Children’s Health

Diabetes in pregnancymanagement of diabetes and its complications

from preconception to the postnatal period

Clinical GuidelineMarch 2008 (revised reprint July 2008)Funded to produce guidelines for the NHS by NICE

RCOG

Press

2008RCOG Press

Published by the Royal College of

Obstetricians and Gynaecologists.

To purchase further copies and for

a complete list of RCOG Press titles,

visit: www.rcogbookshop.com

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Diabetes in pregnancymanagement of diabetes and its complications

from preconception to the postnatal period

ClinicalGuideline

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Other NICE guidelines produced by the National Collaborating Centre for

Women’sand Children’sHealth include:

• Antenatal care: routine care for the healthy pregnant woman

• Fertility: assessment and treatment for people with fertility problems

• Caesarean section

• Type 1 diabetes: diagnosis and management of type 1 diabetes in children

and young people

• Long-acting reversible contraception: the effective and appropriate use of

long-acting reversible contraception

• Urinary incontinence: the management of urinary incontinence in women

• Heavy menstrual bleeding

• Feverish illness in children: assessment and initial management in children

younger than 5 years

• Urinary tract infection in children: diagnosis, treatment and long-term

management

• Intrapartum care: care of healthy women and their babies during childbirth

• Atopic eczema in children: management of atopic eczema in children from

birth up to the age of 12 years

• Surgical management of otitis media with effusion in children

Guidelines in production include:

• Induction of labour (update)

• Surgical site infection

• Diarrhoea and vomiting in children under 5

• When to suspect child maltreatment

• Meningitis and meningococcal disease in children

• Neonatal jaundice

• Idiopathic constipation in children

• Hypertension in pregnancy

• Socially complex pregnancies

• Autism in children and adolescents

Enquiries regarding the above guidelines can be addressed to:

National Collaborating Centre for Women’sand Children’sHealth

King’s Court

Fourth Floor

2–16 Goodge Street

London

W1T 2QA

[email protected]

A version of this guideline for women with diabetes and the public is available from the NICE

website (www.nice.org.uk/CG063) or from NICE publications on 0845 003 7783; quote reference

number N1485.

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NICE 2008

The 2 hour 75g oral glucose tolerance test (OGTT) should be used to test for GDM WHO criteria

Women with any risk factor OGTT at 24-28 weeks

GDM in previous pregnancy early self monitoring of blood glucose or

OGTT at 16-18 weeks and

OGTT at 28 weeks if results normal

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NICE 2008

The WHO definition of GDM encompasses both impaired glucose tolerance (IGT) and diabetes.

World Health Organization and Department of Noncommunicable Disease Surveillance. Definition, diagnosis and classification of diabetes

mellitus and its complications. Report of a WHO consultation. Part 1: diagnosis and classification of diabetes mellitus. Geneva: World Health

Organization; 1999.

IGT: fasting < 7.0 mmol/l, 2 hour ≥ 7.8 mmol/l Diabetes: fasting ≥ 7.0 mmol/l, 2 hour ≥ 11.1 mmol/l

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Risk factors for GDM

BMI > 30 kg/m2

Previous baby ≥ 4.5 kg

Previous GDM

Family history of DM (first-degree relative with DM)

Family origin with a high prevalence of DM: South Asian

specifically women whose country of family origin is India, Pakistan or Bangladesh

Black Caribbean

Middle Eastern family origin

specifically Saudi Arabia, United Arab Emirates, Iraq, Jordan, Syria, Oman, Qatar, Kuwait, Lebanon or Egypt

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NICE 2008

Approximately 20–50% of women will have a positive screening result using these risk factors

Proportions will be varying considerably from one geographical area to another

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Ethnicity

Systematic review of 13 studies:

Non-white race/ethnicity most consistent predictor of future recurrence

Recurrence rates

52–69% in the minority ethnic populations

30–37% in non-Hispanic white populations

Kim C, Berger DK and Chamany S. Recurrence of gestational diabetes mellitus: a systematic review. Diabetes Care 2007;30(5):1314–19.

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Ethnic risk of GDM

11x in Indians

8x in South East Asians

6x in Arabs/Mediterraneans

3x in Afro-Caribbeans

highest prevalence of GDM in inner city areas

Nelson-Piercy C.Diabetes mellitus in Handbook of Obstetric Medicine, Fourth Edition, 2010

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Previous GDM and recurrence rate

Recurrence of the GDM is 30–84%

75–77% in case of insulin-treatment in a previous pregnancy

Major CA, DeVeciana M, Weeks J, et al. Recurrence of gestational diabetes: who is at risk? American Journal of Obstetrics and Gynecology

1998;179(4):1038–42.

Spong CY, Guillermo L, Kuboshige J, et al. Recurrence of gestational diabetes mellitus: identification of risk factors. American Journal of

Perinatology 1998;15(1):29–33.

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Age – risk factor?

….. new research shows that maternal age, alone and

in correlation with the maternal racial origin, may also be a significant factor contributing to the development of GDM.

Makgoba M, Savvidou M, Steer P. An analysis of the interrelationship between maternal age, body mass index and racial origin in the development of gestational diabetes mellitus. BJOG 2011; DOI: 10.1111/j.1471-0528.2011.03156.x.

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Easy to prevent?

Mike Marsh, Deputy Editor-in-Chief of BJOG:

“It is crucial that women are aware of the benefits of healthy eating and weight control prior to pregnancy as this may reduce the risk of them developing diabetes in pregnancy.

Avoiding being overweight prior to pregnancy is particularly important for older women of South Asian and Black African racial origin.”

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Does treatment help ?

ACHOIS trial RCT, 2005 (GDM defined as per WHO)

490 women with IGT in the treatment group

510 women with IGT receiving routine care

Treating GDM improves outcomes for women and babies

the rate of serious perinatal outcomes

1% intervention group vs. 4% controls, P = 0.01

34 needed to treat to prevent a serious outcome in a baby

Crowther CA, Hiller JE, Moss JR, et al.; Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS) Trial Group. Effect of

treatment of gestational diabetes mellitus on pregnancy outcomes. New England Journal of Medicine 2005;352(24):2477–86.

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Counseling for GDM

Good glycaemic control reduces risk of fetal macrosomia

trauma during birth (to themselves and the baby)

induction of labour or caesarean section

neonatal hypoglycaemia and perinatal death

Crowther CA, Hiller JE, Moss JR, et al.; Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS) Trial Group. Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. New England Journal of Medicine 2005;352(24):2477–86.

The role of diet, body weight and exercise may prevent or delay development of DM 2 in later life

risk doubled for each stone gained

risk 40-60% in next 10-15 years

Nelson-Piercy C. Diabetes mellitus in Handbook of Obstetric Medicine, Fourth Edition, 2010

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Counseling - Blood glucose monitoring

Blood glucose targets during pregnancy for women with DM (including GDM) preprandial 3.5–5.9 mmol/l

1 hour postprandial < 7.8 mmol/l

Recommended self-monitoring of blood glucose fasting blood glucose and 1 hour after meal

in insulin-treated DM advise to test blood glucose before going to bed at night

National Institute for Clinical Excellence. Diabetes in Pregnancy: Management of Diabetes and Its Complications from Preconception to the

Postnatal period: Guideline CG63. London, England: National Institute for Clinical Excellence, 2008.

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Counseling - Diet

The goals - optimisation of glycaemic control

Avoid postprandial hyperglycaemia ! an important aim of dietary therapy is reducing postprandial

glucose levels

de Veciana M, Major CA, Morgan MA, et al. Postprandial versus preprandial blood glucose monitoring in women with gestational

diabetes mellitus requiring insulin therapy. New England Journal of Medicine 1995;333(19):1237–41.

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GDM - Diet

82% - 93% of women with GDM will achieve blood glucose targets on diet alone carbohydrates from low glycaemic index sources

lean proteins including oily fish

balance of polyunsaturated fats and monounsaturated fats

If BMI > 27 kg/m2 restrict calorie intake to 25 kcal/kg/day or less

does not result in ketonemia



Moses RG, Barker M, Winter M, Petocz P, Brand-Miller JC. Can a low- glycemic index diet reduce the need for insulin in gestational diabetes

mellitus? A randomized trial. Diabetes Care 2009;32:996–1000. doi:10.2337/dc09-0007

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Diet in pre – existing DM

Women with pre-existing DM will have received extensive advice about dietary management

Women with DM 1 will have been on a structured education course Dose Adjustment for Normal Eating (DAFNE) Offer course to those not trained as a matter of urgency

6/12 after the course the mean HbA1c fell by 1%

Structured education programmes for DM 2 X-PERT

DAFNE Study Group. Training in flexible, intensive insulin management to enable dietary freedom in people with type 1 diabetes: dose adjustment for normal eating (DAFNE) randomised controlled trial. BMJ 2002;325:746–8. doi:10.1136/bmj.325.7367.746 Deakin TA, Cade JE, Williams R, Greenwood DC. Structured patient education: the Diabetes X-PERT Programme makes a difference. Diabet Med 2006;23:944–54. doi:10.1111/j.1464-5491.2006.01906.x

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Composition of the diet

Dietary advice for pregnant women with DM

(modified from Nutrition Subcommittee

of the Diabetes Care Advisory Committee

of Diabetes UK)

Nutrition Subcommittee of the Diabetes Care Advisory Committee of Diabetes UK. The implementation of nutritional advice for people with diabetes. Diabet Med 2003;20:786–807. doi:10.1046j.1464-5491.2003.01104.x

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When to start hypoglycemic therapy?

Diet and exercise fail to maintain blood glucose targets during a period of 1–2 weeks

Ultrasound investigation suggests incipient fetal macrosomia AC > 70th percentile



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What treatment? NICE 2008

Clinically effective therapy includes oral agents (metformin and glibenclamide)

insulin therapy

regular human insulin or rapid- acting insulin analogues

Health economic analysis glibenclamide is cost- effective

lack of clinical evidence from NHS setting

RCT investigating metformin is due to report (MiG)

Therapy should be individually tailored


Postnatal period: Guideline CG63. London, England: National Institute for Clinical Excellence, 2008

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Treatment - Oral agents (update)

Glibenclamide (Glyburide) shorter-acting sulfonylurea in 2000 - same outcomes as insulin treatment (4% switched to insulin)

safe for most GDM and some DM 2 less episodes of hypoglycaemia than insulin and more convenient

new RCT 2010

women with GDM randomised to metformin or glibenclamide 35% of the metformin group required insulin 16% of the glibenclamide group required insulin

Langer O, Conway DL, Berkus MD, Xenakis EM, Gonzales O. A comparison of glyburide and insulin in women with gestational diabetes mellitus. N Engl J Med 2000;343:1134–8. Moore LE, Clokey D, Rappaport VJ, Curet LB. Metformin compared with glyburide in gestational diabetes. A randomised controlled trial. Obstet Gynecol 2010;115:55–9. doi:10.1097/AOG.0b013e3181c52132

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Treatment - Oral agents (update)

MiG trial 2008 Metformin – biguanide

safe and effective in GDM in the second half of pregnancy

perinatal outcomes similar

lower incidence of

PIH, pre-eclampsia, hypoglycaemia

lower postprandial glucose, lower maternal weight

46% needed insulin to achieve adequate control

With lower glycaemic targets achieved = less complication

birth weight >4kg, pre-eclampsia, prematurity

Follow-up after 2 years

better subcutaneous to visceral fat ratio

Rowan JA, Hague WM, Gao W, Battin MR, Moore MP; MiG Trial Investigators. Metformin versus insulin for the treatment of gestational

diabetes. N Engl J Med 2008;358:2003–15.

Rowan JA, Gao W, Hague WM, McIntyre HD. Glycemia and its relationship to outcomes in the metformin in gestational diabetes trial. Diabetes

Care 2010;33:9–16

Rowan JA et al. Diabetes Care 2011;34:2279

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Insulin. NICE 2008

Rapid-acting insulin analogues aspart and lispro – benefits compared with regular insulin

outside pregnancy (also demonstrated in the pregnant population)

fewer episodes of hypoglycaemia

reduction in postprandial glucose excursions

improvement in overall glycaemic control

Long-acting insulin analogues Still unclear safety of the long actin insulin analogue – glargin

isophane insulin (NPH) remains the first choice in pregnancy



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Insulin regimen

RCT (392 patients) insulin four times daily vs. insulin twice daily four-times-daily insulin

improves glycaemic control and perinatal outcomes does not increase the risks of maternal hypoglycaemia and caesarean

section

CSII should be offered if adequate control is not obtained

without disabling hypoglycaemia

In insulin-treated DM - provide concentrated glucose solution

in type 1 DM give also glucagon

Nachum Z, Ben Shlomo I, Weiner E, et al. Twice daily versus four times daily insulin dose regimens for diabetes in pregnancy: randomised controlled trial. British Medical Journal 1999;319(7219):1223–7.

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Fetal growth and wellbeing

USS 4 weekly fetal growth and AFI from 28 to 36 weeks

Monitoring of fetal wellbeing before 38 weeks is not recommended (unless IUGR)

Contact with the diabetes care team every 1–2 weeks throughout pregnancy



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Preterm labour and DM

Steroids and tocolysis can be used

additional insulin and close monitoring if treated by steroids

sliding scale vs. outpatient regimes

betamimetic drugs should not be used for tocolysis

National Institute for Clinical Excellence. Diabetes in Pregnancy: Management of Diabetes and Its Complications from Preconception

to the Postnatal period: Guideline CG63. London, England: National Institute for Clinical Excellence, 2008

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Timing and mode of birth

Elective IOL or CS (if indicated) after 38 weeks if uncomplicated pregnancy

reduces the risk of stillbirth and shoulder dystocia

does not increase CS rate

VBAC – no contraindication

Macrosomia discuss the risks and benefits of vaginal birth, IOL and CS



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Hyperglycaemia intrapartum

Risk of fetal hypoglycaemia post partum response to poorly controlled DM

response to maternal hyperglycaemia during the labour

Maternal hyperglycaemia associated with fetal distress

CEMACH 47% of the women with DM 1 and 41% with DM 2 had sub-

optimal glycaemic control during labour and birth (P = 0.28)

Confidential Enquiry into Maternal and Child Health. Diabetes in pregnancy: are we providing the best care? Findings of a national enquiry:

England, Wales and Northern Ireland. London: CEMACH; 2007.

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Glycaemic control during labour and birth

Women with DM monitor capillary blood glucose on an hourly basis

aim for blood glucose 4 - 7 mmol/l

Women with DM 1 i.v. dextrose and insulin if blood glucose is not 4 - 7 mmol/l



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Post partum - Breastfeeding

Breastfeeding probably doesn't affect glycaemic control

no high-quality studies

lower FBG 6/52 post partum in those exclusively breastfeeding

compared with those who stopped breastfeeding before 6/52 post partum or with those who bottle - fed

Ferris AM, Dalidowitz CK, Ingardia CM, et al. Lactation outcome in insulin-dependent diabetic women. Journal of the American Dietetic Association 1988;88(3):317–22.

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Post partum - Management

GDM stop hypoglycaemic treatment immediately after birth

Insulin-treated pre-existing DM reduce insulin immediately after birth and monitor blood glucose levels

carefully to establish the appropriate dose inform about risk of hypoglycaemia in the postnatal period

especially when breastfeeding advise to have a meal or snack available before or during feeds

DM 2 and breastfeeding can resume or continue to take metformin/glibenclamide immediately

but other oral hypoglycaemic agents should be avoided while breastfeeding

Women with diabetes who are breastfeeding avoid any drugs for the treatment of DM complications that were

discontinued for safety reasons in the preconception period National Institute for Clinical Excellence. Diabetes in Pregnancy: Management of Diabetes and Its Complications from Preconception to the Postnatal period: Guideline CG63. London, England: National Institute for Clinical Excellence, 2008

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Follow - up after birth

Pre-existing DM refer back to their routine diabetes care arrangements

GDM exclude persisting hyperglycaemia before transfer to community care

remind of the symptoms of hyperglycaemia

offer lifestyle advice

including weight control, diet and exercise

FBG 6/52 post partum and annually thereafter

inform about the risks of GDM in future pregnancies

screening for DM when planning future pregnancies

OGTT or fasting plasma glucose

early blood glucose self-monitoring or an OGTT in future pregnancies

subsequent OGTT at 28/40 if normal results

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Planning of pregnancy

importance of contraception

need for preconception care

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Update since NICE 2008 guideline - HAPO

The multinational Hyperglycaemia and Pregnancy Outcome (HAPO) study defined the relationship of maternal glucose tolerance to

neonatal outcomes in over 23000 women

linear relationship between maternal fasting and postprandial glucose level and birth weight above 90th centile

same apply to adiposity

no apparent threshold effect

HAPO Study Cooperative Research Group, Metzger BE, Lowe LP, Dyer AR, Trimble ER, Chaovarindr U, Coustan DR, et al. Hyperglycemia and

adverse pregnancy outcomes. N Engl J Med 2008;358:1991–2002.

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Update since NICE 2008 guideline - IADPSG

The International Association of Diabetes and Pregnancy Study Groups

consensus report 2010

effort to achieve international consensus

radical redrawing of diagnosis and screening

dg levels set at the levels of blood glucose at which adverse outcomes (LGA, cord C

peptide and newborn fat >90th C) are increased 1.75 fold over the mean from HAPO

test for all population

expected incidence of GDM over 16% !!!

International Association of Diabetes and Pregnancy Study Groups Consensus Panel, Metzger BE, Gabbe SG, Persson B, Buchanan TA, Catalano

PA, Damm P, et al. International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of

hyperglycemia in pregnancy. Diabetes Care 2010;33:676–82.

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Update since NICE 2008 guideline - SIGN

Scottish guidelines adopted IADPSG criteria oGTT for high risk women

fasting glucose for low risk women

Scotish Intercollegiate Guidelines Network. National clinical guideline 116: Management of diabetes. Edinburgh: SIGN; 2010

[http://www.sign.ac.uk/pdf/sign116.pdf].

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Current challenges

How to translate the results of trials into the practice? probably no more studies without dg or treatment of diabetes

Major increase in incidence but probably only 8-20% would need insulin or oral treatment

Can we indicate high risk women for intensive intervention?

low risk group which does not need testing?

Dietary changes in larger proportion of pregnant women Would it be beneficial?

Would it prevent GDM and complications?

Can we influence the health of the next generation?

Diagnosis and Treatment of Gestational Diabetes, RCOG, Scientific Advisory Committee Opinion Paper 23, January 2011

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