Guia Diabetes Gestacional

8/3/2019 Guia Diabetes Gestacional

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Global Guideline

Pregnancyand diabe tes

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The mission of the International Diabetes Federation is to promotediabetes care, prevention and a cure worldwide

International Diabetes Federation, 2009All rights reserved. No part of this publication maybe reproducedor transmitted in any form or by any means without the written

prior permission ofthe International Diabetes Federation (IDF).

Requests to reproduce or translate IDFpublications should be addressed toIDF Communications, Chausse de la Hulpe 166, B-1170 Brussels,Belgium,

by e-mail tocom m [email protected],or by fax to +32-2-5385114.

This guideline was supported by an unrestricted educational grant from Eli Lillyand Company.This company had no involvement in the writing, review andapproval ofthe manuscript.

Citation

IDF ClinicalGuidelinesTask Force.Global Guideline on Pregnancy and Diabetes.Brussels:International Diabetes Federation, 2009.

This and other IDFpublications areavailablefrom: International DiabetesFederationChausse de la Hulpe 166B-1170 BrusselsBelgiumTel: +32-2-5385511Fax:+32-2-5385114ww w.idf.org

mailto:[email protected]:[email protected]:[email protected]://www.idf.org/http://www.idf.org/http://www.idf.org/http://www.idf.org/mailto:[email protected]


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Global Guideline on Pregnancy and Diabetes

Members ofthe

Writing Group

Nam Han Cho (South

Korea) StephenColagiuri

(Australia) Lois Jovanovic

(USA)

Robert Moses (Australia)(Chair)

MariaInsSchmidt(Brazil)

Medical Writer

Elizabeth Home (UK)

Members oftheExpert ReviewCommittee

Edward Coetzee (South Africa)

Donald Coustan (USA)

Moshe Hod (Israel)

Dorte Jensen

(Denmark)

Terence Lao (Peoples Republic ofChina)

GloriaLpez-Stewart

(Chile) Sara Meltzer

(Canada) IngvarsRasa

(Latvia)

Veerasamy Seshiah(India)


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Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .4

2. Gestational diabetes mellitus (GDM) .. . . . . . . . . . . . . . . . . . . . . . .5

6. Recommendations for Standard Care . . . . . . . . . . . . . . .. . .18

Pre-pregnancy counselling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . .18

At first prenatal visit . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 19

2.1 Defining the condition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 5 Frequency of subsequent visits . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . 20

2.2 Diagnosisof GDM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . .. . 5

2.3 Rationale fortreating GDM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . 5

3. Before pregnancy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .6

3.1 General issues fordifferent groups

of women . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

3.2 Review of medications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 7

3.3 Pre-conception glycaemic control . . . . . . . . . . . . . . . . . . . . . . .. . . . . . .

8

4. During pregnancy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .9

4.1 Testing ofal l or some women forGDM . . . . . .. . . .. . 9

Ongoing management ofdiabetesduring pregnancy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . 20

Management of gestational diabetes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21

After delivery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . 22

Breastfeeding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . 22

Follow-up within 6 weeks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .22

7. Implementation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . .23

8. Evaluation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .23

4.2 Testing forGDM a two-stage or

one-stage procedure? . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . 10

4.3 Management during pregnancy . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . 10

5. After pregnancy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .16

5.1 Breastfeeding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. .

. .

5.2F

upGDM. .. .. .. .

16

5.3P

on of type 2 diabetes inwomen

who developed GDM . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . 17


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9. References. . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .24

3



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1. IntroductionPregnancy is associated with changes in insulin sensitivity which

may lead to changes in plasma glucose levels. For women withknown diabetes or forwomen who develop diabetes during the

pregnancy, these changes canput outcomes at risk. Thisguideline deals with the means of identifying women forwhom

such problems are new, and helping them, as well as womenalready known to have diabetes, to achieve the desiredoutcome ofa healthy mother and baby.Within the IDF Global Guideline forType 2 Diabetes of

2005 [1] there was a section on pregnancy, but this did notaddress type 1 diabetes and did not consider the wider issues

surrounding gestational diabetes mellitus (GDM) and preventionofdiabetes.The current guidelineincludes these additional topics,and attempts to present some of the evidence bearing on areasofcontroversy.

Since 2005 an evidence-based guideline on diabetes inpregnancyhas been published in the UK [2], the Canadian evidence-based

diabetes guideline (including pregnancy) has been revised [3], andthere have been furtherdeliberations on the implications of the

Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study[4]. In preparing the current guideline, a non-formal evidencereview was circu- lated to, and discussed by, a small WritingGroup in March

2009, then redraftedbeforecirculation to an ExpertReviewCommittee.The revised draft was referred to IDF member

organizations for comments.This document represents the finalrevision which has taken into consideration comments receivedfrom this wide consultation.

The aim was to draw up a set of recommendations for StandardCare as envisaged in the 2005 Global Guideline [1] and whichrepresents current best practice. It is acknowledged that due tolimited human and material resources, many countries or healthsystems will not be able to implement all of the

recommendations in this Guideline. The Recommendations are presented together towards the end of the document (section6).The topics covered in this Guideline have in general been presented in the order encountered before, during, and afterpregnancy, except that gestational diabetes is introduced first.

El embarazo se asocia a los cambios en la sensibilidad de lainsulina que puede llevar a los cambios en niveles de la glucosadel plasma. Para las mujeres con diabetes sabida o para lasmujeres que desarrollan la diabetes durante el embarazo, estoscambios pueden poner resultados a riesgo. Esta pauta se ocupade los medios de identificar a las mujeres para quienes talesproblemas son nuevos, y de ayudarlas, as como las mujeresconocidas ya para tener diabetes, para alcanzar el resultadodeseado de una madre y de un beb sanos.

Dentro de la pauta global de la CA para el tipo - diabetes 2 de 2005[1] haba una seccin en embarazo, pero ste no trat la diabetesdel tipo 1 y no consideraba las ediciones ms anchas mellitus dediabetes gestacional circundante (GDM) y prevencin de ladiabetes. La pauta actual incluye estos asuntos adicionales, eintenta presentar algo de la evidencia concerniente reas de lacontroversia.

Desde 2005 que una directriz evidencia-basada sobre la diabetes enembarazo se ha publicado en el Reino Unido [2], la pauta evidencia-basada canadiense de la diabetes (embarazo incluyendo) se ha revisado

[3], y ha habido otras deliberaciones en las implicaciones de lahiperglucemia y del estudio adverso del resultado del embarazo(HAPO) [4]. En la preparacin de la pauta actual, una revisin no-formal de la evidencia era circu- lated a, y discutido cerca, un pequeo

grupo de la escritura en marzo 2009, entonces rehecho antes de lacirculacin a una revisin experta El bosquejo revisado Committee.The

era organizaciones referidas del miembro de la CA para loscomentarios. Este documento representa la revisin final que ha tomado

en los comentarios de la consideracin recibidos de esta consultaamplia.

La puntera era elaborar un sistema de las recomendaciones para elcuidado estndar segn lo considerado en la pauta global 2005 [1] y querepresenta mejor prctica actual. Es la CA knowledged que debido a las

fuentes re- humanas y materiales limitadas, a muchos pases o asistemas de la salud no pueda ejecutar todas las recomendaciones en

esta pauta. Las recomendaciones se presentan juntas hacia el extremodel documento (asuntos de la seccin 6).The cubiertos en esta pauta engeneral se han presentado en la orden encontrada antes, durante, ydespus de embarazo, salvo que la diabetes gestacional se introduce

primero.


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. Gestational diabetes

mellitus (GDM)2.1 Defining the condition

The widely accepted definition is that given by the AmericanDiabetes Association (ADA) any degree of glucose intolerance withonset or first recognition during pregnancy [5].The definition isapplicable even if the conditionpersists afterpregnancy.It does not

exclude the possibil ity that unrecognized glucose intolerance may haveante dated or begun concomitantly with the pregnancy. The widespread

acceptance ofthis definitionis in no smallpart due to the fact that it doesnot mention any specific diagnostic criteria.

Any definition of GDM has to take into account three elements of risk of perinatal morbidity and mortality in the currentpregnancy, of themotherdeveloping type 2 diabetes, and ofintrauterineprogrammingofthe

developing fetuswith subsequent expressionofdisordersin laterlife.

2.2 Diagnosis of GDMThere is a continuum of risk for maternal glucose levels and, at least,adverse pregnancy outcomes [6-11]. Currently there is a lack of

international consensus regarding the diagnostic criteriaforGDM.In most

parts of the world the diagnostic criteria are based on either the 100gram 3-hour test as commonly used in the USA or the 75 gram 2-hour

World Health Organization (WHO) test. Many national bodies have

derivedtheirown criteria based on localexperience and theirhealthcaredelivery systems.This lack of consensus may well be addressed by

recommendations arising from the International Association of Diabetesin Pregnancy Study Groups (IADPSG), a working group analysing the

results of the HAPO study.Any recommendations from this group willthen need to be considered by relevant national bodies and incorporated

into the local health service arrangements.This process will take sometime. Other than by chance, it is not clear if any diagnostic criteria of

GDM based exclusively on pregnancy outcomes will be applicable to theother two elements of risk.

Mellitus de diabetes gestacional (GDM)

2.1 Definicin de la condicin La definicin extensamenteaceptada es sa dada por el `americano de la asociacin de ladiabetes (ADA) cualquier grado de intolerancia de la glucosacon inicio o de primer reconocimiento durante el pregnancy [5]. Ladefinicin es aplicable incluso si persiste el `la condicin despusde que el `de pregnancy'. l no excluya la posibilidad que laintolerancia desconocida de la glucosa puede tener anticuadoapuesta en el pquer o comenzado concomitante con el embarazo.'La aceptacin extensa de esta definicin est en ninguna pequeaparte debido al hecho de que no menciona ninguna criterios dediagnstico especfica. Cualquier definicin de GDM tiene queconsiderar tres elementos del riesgo - de morbosidad y demortalidad perinatales en el embarazo actual, del tipo que seconvierte de la madre - la diabetes 2, y de la programacinintrauterina del feto que se convierte con la expresin subsecuentede desordenes en vida posterior.

2.2 Diagnosis de GDMHay una serie continua de riesgo para los niveles maternales y, porlo menos, los resultados adversos del embarazo [6-11] de laglucosa. Hay actualmente una carencia del consenso internacionalcon respecto a los criterios de diagnstico para GDM. En mayorespartes del mundo los criterios de diagnstico se basan en la prueba

de tres horas de 100 gramos como de uso general en los E.E.U.U. ola Organizacin Mundial de la Salud de dos horas de 75 gramos(WHO) pruebe. Muchos organmismos nacionales han derivado suspropios criterios basados en experiencia local y sus sistemas deenvo del cuidado mdico. Esta carencia del consenso se bienpuede tratar por las recomendaciones que se presentan de laasociacin internacional de la diabetes en los grupos de estudio delembarazo (IADPSG), grupo de trabajo que analiza los resultadosdel estudio de HAPO. Cualquier recomendacin de este grupoentonces necesitar ser considerada por los organmismos

nacionales relevantes y ser incorporada en los arreglos locales deAR del servicio mdico. Este proceso tardar una cierta hora. Conexcepcin de por casualidad, no est claro si algunos criterios dediagnstico de GDM basado exclusivamente en resultados delembarazo son aplicables a los otros dos elementos del riesgo.


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5

2.3 Rationale for treating GDM

It is generally acknowledged that women with GDM are atincreased risk of adverse pregnancy outcomes, particularly

relating to perinatal mortality and morbidity. It is also generallyacknowledged that treatment of women with GDM, by whatevermeans, can reduce the risk of these problems. In the developedworld an increasedperinatal mortality rate is unlikely but can stillbe demonstrated in a sufficiently large series [12]. However, insettings where obstetric care does not uniformly reach modernquality standards, perinatal mortality is still an important issue[13].

Perinatalmorbidity is an ongoing concern. Macrosomicorlarge forgestational age (LGA) infants are still common, and can beconsidered a surrogate marker forat least some of the effects of

intra-uterine programming.2.3 Anlisisrazonado para tratar GDM Se reconoce generalmenteque las mujeres con GDM estn en el riesgo creciente deresultados adversos del embarazo, la igualdad ticularly referentes

a mortalidad perinatal y la morbosidad. Tambin se reconocegeneralmente que tratamiento de mujeres con GDM, porcualesquiera medios, pueden reducir el riesgo de estos problemas.En el mundo desarrollado una tarifa de mortalidad perinatalcreciente es inverosmil pero se puede todava demostrar en unaserie suficientemente grande [12]. Sin embargo, en los ajustesdonde el cuidado obsttrico no alcanza uniformemente normas decalidad modernas, la mortalidad perinatal sigue siendo una edicinimportante [13]. La morbosidad perinatal es una preocupacin encurso. Macrosomic o grandes para los nios de la edad gestacional

(LGA) sigue siendo campo comn, y se puede considerar unmarcador sustituto por lo menos algunos de los efectos de la programacin intrauterina.

An earlierprospective controlled trial demonstrated that tightcontrol, with a high rate of insulin use, improved perinataloutcomes [14]. Later, a prospective non-randomized interventionstudy demonstrated forwomen with GDM that intensive control

(versus conventional control) improved perinatal outcomes to alevel that was comparable to a group without GDM [15]. Thehazards of a late diagnosis ofGDM, and thereforeeffectively notreatment, have been outlined [16].The Australian CarbohydrateIntolerance Study in Pregnancy (ACHOIS), a blinded randomizedtrialincluding1000 women, designed to examine whether the treatment ofwomen withGDM would reduce perinatalcomplications, found asignificant reduction in serious perinatal complications in thetreated group [17]. Recently the results of the Maternal-FetalMedicine Unit (MFMU) Network study have becomeavailable.Treating women withdesignated mild GDM lowered theriskformany adversepregnancy outcomes [18].Limited observational studies in humans strongly suggest that any

pregnancy complicated by hyperglycaemia confers a risk to theoffspringofdeveloping type 2 diabetes [19-24], and that improvingmaternal glycaemic control may reduce this risk. However, thelong follow-up necessary makes it unlikely that any randomizedcontrolled trial (RCT) evidence will be forthcoming in theforeseeablefuture.

Un ensayo controlado anticipado anterior demostr que el control deltight del `, con una alta tasa de uso de la insulina, mejor los resultadosnatales del peri- [14]. Ms adelante, un estudio no-seleccionado al azaranticipado de la intervencin demostr para las mujeres con GDM que el

control intensivo (contra control convencional) mejor resultadosperinatales a un nivel que era comparable a un grupo sin GDM [15]. Lospeligros de una ltima diagnosis de GDM, y por lo tanto con eficacia deningun tratamiento, se han contorneado [16]. El estudio australiano enel embarazo (ACHOIS), un ensayo seleccionado al azar cegador de laintolerancia del carbohidrato incluyendo 1000 mujeres, diseadas paraexaminar si el tratamiento de mujeres con GDM reducira complicacionesperinatales, encontraron una reduccin significativa en tions perinatalesserios del complica- en el grupo tratado [17]. Los resultados del estudioMaternal-Fetal de la red de la unidad de la medicina (MFMU) han estado

recientemente disponibles. Tratar a mujeres con el mild sealado GDMdel `baj el riesgo para muchos resultados adversos del embarazo [18].Los estudios de observacin limitados en seres humanos sugierenfuertemente que cualquier embarazo complicado por hiperglicemiaconfiera un riesgo al descendiente de desarrollar el tipo - diabetes 2 [19-24], y que la mejora de control glycaemic maternal puede reducir esteriesgo. Sin embargo, la carta recordativa larga necesaria hace inverosmilque cualquier evidencia de ensayo controlada seleccionada al azar (RCT)ser prxima en el futuro prximo.


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3. Before pregnancy3.1 General issues for different groupsof women

All women contemplating a pregnancy should ideally havepre-conception advice from a healthcare professional. This isparticularlyimportantforwomen who currently have diabetesor intermediate degrees of hyperglycaemia (impaired glucosetolerance IGT, or impaired fasting glucose IFG), or haveexperienced GDM in aprevi- ous pregnancy.

Women with GDM in a previous pregnancy should have had

their glycaemic status clarified in the postpartum period.Theprobability ofdeveloping GDM in a subsequent pregnancy is of

the order of 30% to 50% [25]. I f more than a year has passed

since the postpartum assessment, then these women shouldhave an oral glucose tolerance test (OGTT) prior to

conception or at least in the first trimester. If the glycaemicstatus is then normal, the OGTT should be repeated at around

26 to 28 weeks, or at an earlier time if clinically indicated.These indications may include, but are not limited to, the

development of glycos- uria, increased amniotic fluid or asuspicion of increased fetal size.Women with previous GDM

who are shown to have normal glucose tolerance postpartum,and women withpreviousGDM who experience a recurrence,

do not appear to be at increased risk of first trimester

malformations other than the risks associated with obesity.

. Antes de embarazo 3.1 Ediciones generales para

diversos grupos de mujeres Todas las mujeres quecomtemplan un embarazo deben idealmente tener

consejo de la preconcepcin de un profesional delcuidado mdico. Esto es particularmente importante para

las mujeres que tienen actualmente diabetes o gradosintermedios de hiperglicemia (tolerancia deteriorada de

la glucosa - IGT, o del de ayuno deteriorado IFG de la

glucosa), o ha experimentado GDM en un embarazo delous del previ-. Las mujeres con GDM en un embarazo

anterior deben haber hecho su estado glycaemic aclarar

en el riod postparto del PE. La probabilidad dedesarrollar GDM en un embarazo subsecuente est de laorden de el 30% hasta el 50% [25]. Si ms que un ao ha

pasado desde el gravamen postparto, despus estasmujeres deben tener una prueba de tolerancia de glucosa

oral (OGTT) antes del concepto o por lo menos en el primer trimestre. Si el estado glycaemic es entonces

normal, el OGTT se debe repetir aproximadamente 26 a

28 semanas, o en un rato anterior si clnico indicado.Estas indicaciones no se pueden incluir, sino limitar a, el

desarrollo del uria del glycos-, lquido amniticocreciente o una suspicacia del tamao fetal creciente. Las

mujeres con GDM anteriores que se demuestren paratener tolerancia normal de la glucosa postparto, y las

mujeres con GDM anteriores que experimenten unarepeticin, no aparecen estar en el riesgo creciente de

primeros tions del malforma- del trimestre con excepcinde los riesgos asociados a obesidad.


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Women already known to have diabetes (sometimes called pre-gestational diabetes in this context) need to consider how the effectsof their pregnancy may impact on the diabetes, and on any of theirdiabetes-associatedproblems.Hypoglycaemiais more likely to occur in

pregnancy,especiallyin the firsttrimester, as a greatereffortis made toattain and maintain glycaemiccontrol.A variable dietary intakeassociated with morning sickness may also increase this tendencytowards hypoglycaemia.Women with established diabetic complications,such as retinopa- thy or nephropathy, may experience a worseningduring the pregnancy. These aspects should ideally be assessedpriortoany pregnancy and/or at such intervalsduringthepregnancy as clinicallyindicated.

3.2 Review ofmedications

Women with diabetes or previous GDM may be takingmedications contra-indicated in pregnancy.These

include, but are not limited to, angiotensin convertingenzyme (ACE) inhibitors, angiotensin-II receptorblockers (ARBs), calcium channel blockers and lipidlowering agents.

In a large cohort study of pregnancy which excluded

women with diabetes, first-trimester exposure to ACE

inhibitors was associatedwith an increasedriskofmajor

congenital malformations compared to the use of other

anti-hypertensive agents [26]. If ACE inhibitors werebeing used to treat diabetic nephropathy prior to

pregnancy, then a significant deterioration in proteinuria

can be anticipated during the course of the pregnancyfollowingdiscontinuation [27,28]. This aspect will need to

be considered when offeringadvice.

There are theoretical problems potentially associatedwith the use ofARBs inpregnancy, but only very limiteddata on this topic. Calcium channel blockers have the

potential to cause fetal hypoxia and should be usedcautiously ifat all.

For statins, congenital malformations have been

reported and there is concern that decreasedcholesterolsynthesis may affect fetal development [29], but evidence on use inpregnancy is very limited. Dataon the use of fibrates and niacin are also limited.

These medications need to be stopped as part ofpre-conception planning or as soon as a pregnancy is recog-

nized. Sufficient blood pressure control should besecured by using methyldopa or labetalol.

In common with other women during pregnancy,women with diabetes need to ensure there is an

adequate intake offolic acid.

Women with type 2 diabetes who are taking eithermet-

formin and/orglyburide (glibenclamide)need to have thepotential advantages and disadvantages of these medica-

tions outlined and to continue with them if it is in theirbest interests to do so.

7



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3.3 Pre-conceptionglycaemic control

Women with diabetes have increased risk of an earlymiscarriage and are at increased riskof having a babywith malformations. Both of these risks are associatedwith less than optimal glycaemiccontrol around the time

of conception and in the first trimester. The extentofthe risk is difficult to quantify, but risks appear to beap- proximately equivalent for women with type 1

diabetes and type 2 diabetes.Women with type 2diabetes appearto have a lesseruptake ofpre-conception

counselling [30].

The increased rate of spontaneous miscarriages appearsto be low when the HbA

1c

is modestly raised, and

higherwith increasingly poor glycaemic control [31-

33]. The risks increase rapidly with higher levels ofHbA

1c. The same pattern is also found with respect to

the rate of fetal malformations [34-36]. Women who

improve theirglycaemic control before conception havea reduced rate o f fetalmalformation [37].There appears

to be no level of glycaemic controlbelow which no

increased risk has been observed [38]. Women with

diabetes should be encouraged to obtain the bestpossible glycaemiccontrol before conception,aimingfor,

in the absence ofconfoundingvari- ables that may alter

the accuracy of the assay, an HbA1c


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4. During pregnancy 4.1 Testing of all or somewomen for GDM

There is continuing debate about whether allpregnantwomen should be tested, or whether testing should bedone ifriskfactors are present, or not done i friskfactors

are absent. There is general agreement about the majorrisk factors for GDM. These include but are notlimited to increasing maternal age and weight,previousGDM or a macrosomic infant, family history of

diabetes among first-degreerelatives, andbeingfrom anethnic background with a high prevalence ofdiabetes.While there is no doubt that women with someor al l of these risk factors are more likely to develop

GDM, the reality is that any woman can develop thisproblem. An RCT found that risk-based screeningcompared withuniversalscreeningmissed about halfthewomen with GDM (1.45% vs 2.7%) [40].

An earlier observational study of Caucasian womenwhere all were tested with an OGTT found that the

prevalenceofGDM among women with no riskfactorswas

2.8%.Excluding this low-riskgroup ofwomen would stillrequire 80% ofthe women to be tested and would miss

10% ofall cases of GDM [41].Testing women according

to the older age- based American College ofObstetricians and Gynecologists (ACOG) criteria wouldmissone-thirdofcases and result in minimal cost savings[42]. A later retrospective study found that testing

according to risk factors would require 90% of thepopulation to be tested [43].A complicated scheme has

been

suggested for reducing the number of women requiring

testing [44], but this was considered unlikely to bepractical [45].

There is general consensus that testing should be doneat an early stage of pregnancy ifrisk factors are present,

but onlypoor evidence that interventions initiated at thisearly stage are helpful.

There is insufficient evidence to come to a definitiveopinion on the advantages of selective testing.

However, selective testing could be considered:(a) if there was evidence to show that this process de-

tected the vast majority of women in the populationbeing considered;

(b) if there was evidence that the process ofselection based on risk factors could be conducted with ac-curacy;

(c) ifwomen in the populationbeing considered and not

being tested had a more benign outcome to theirundiagnosed GDM;

(d) if it was deemed cost-effective, or was the onlyoption, within a particular healthcare arrangement.

The limited evidence so far [46] indicates that a sortingsystem cannot be conducted in an efficient manner, andthat women with GDM without risk factors appear tobe no different from women with GDM and riskfactors.


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4.2 Testing for GDM a two-stage or

one-stage procedure?

A definitive diagnosis of GDM is currently made onthe result of an OGTT. Currently, a two-stage

diagnostic procedure is conducted in some parts ofthe world. A two-stage procedure involves a non-

fasting glucose chal- lenge test (GCT) followed by aformal OGTT for women who have a positive result.

The GCT will inevitably miss some women with GDM.In addition, there has been little systematic examinationof:

(a) how many women who are positive on a GCT failtoreturn forthe definitive OGTT;

(b) whether a two-stage procedure delays the

diagnosis and treatment of GDM, and what theeffect of such a possible delay might be.

A one-stage definitive procedure is preferred, but a

two- stage procedure will continue to suit many

healthcare arrangements. Potential adoption of a lowerglucose load (75 g) and a shorter duration of the

testing procedure may lead to a reconsideration aboutthe need fora two- stageprocedure.

4.3 Management duringpregnancy

4.3.1 Monitoringglucose levels

There is strong evidence of a relationshi p between el-evated maternal glucose levels and macrosomia[15,47,48]. Clinical studies where women were

randomized to test either before or after meals havefound that treatment decisions based on thepostprandialglucose levels resulted in fewer complications,

particularly macrosomia [49,50].

One study has found that management based on 1-hrather than 2-h glucose levels resulted in better obstetricoutcomes [51].Women prefer, and are more likely to becompliant with, testing 1 h after a meal [52]. For glucose

tolerant women there was a positive correlationbetween the 1 h postprandial glucose level and the fetal

abdominal circumference [53]. Women with type 1diabetes, who have an LGA infant, are more likely to

have an elevated HbA1c

than those who do not have

an LGA infant [54].The level of HbA

1cin the third trimester has a

strong

correlation with macrosomia but lacks somesensitivity.

A possible explanation is that the postprandial glucose

excursions are more important in pregnancy, andthis is not always being reflected in the HbA

1clevel

[55]. In one study, women with type 1 diabetes who

were tightly controlled, based on fasting andpostprandialglucosegoals, had no LGAbabies [56].

Continuous glucose monitoring can add an extra dimen-sion to self-monitoring and may highlight areas ofboth

unexpected hypoglycaemiaand hyperglycaemia [57,58].

Whenever it ispossible, pregnant women with diabetesshould be encouraged to self-monitor blood glucoselevelsboth fastingandpostprandial,preferably 1 h after a

meal. The target glucose levels should be as low aspossible compatible with patient comfort and safety.

The conclu- sions of the Fifth International Workshop-

Conference on Gestational Diabetes Mellitus [59], inthe absence of specific evidence, referred to upperboundary treatment targets for capillary blood glucose

levels: fasting90 to 99

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mg/dl (5.0 to 5.5 mmol/l),1 h after starting a meal


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from tablets orelecting to be treated with insu lin, ifdiet

alone is inadequate, will also need careful advice abouttheir carbohydrate choices.The same observationsabout carbohydrate regulation apply to women

diagnosed with GDM [60,61].

There may be an involuntary decrease in energy intakeat the beginning of the pregnancy related to nausea.Later in pregnancy the total energy requirements are

likely to increase. For those women who are insulintreated, there is likely to be an increase in the total dose

of insulin during the pregnancy related to thephysiological decrease in insulin sensitivity.Thus thedietary carbohydrate content and distribution will needto be changing to fulfil nutritional requirements and as the

insulin dose and type are changed.

It is possible that maternal obesity could be associated

with an increased risk of fetal abnormalities [62,63].Weightloss diets are in general not recommended during

the course of a pregnancy. However, at least forwomen with GDM who are considerably overweight,

reducing energy intake by no more than 30% of

habitual intake [64] is not associated with ketosis anddoes not cause harm [65,66].

Theproportionofenergy intakederivedfrom carbohy-drates willvary depending on the traditionaldiet and the

availabil ity ofalternative sources ofenergy. Regulatingandpotentially reducing the carbohydrate intake is aneffective strategy for helping to control glucose levels

[67,68]. Changing the nature ofthe carbohydrates con-

sumed, particularly with respect to the use of foodswith a low glycaemic index (GI), can reduce the

postprandial glucose excursions. For women with

GDM, postprandial glucose elevations are associatedwith adverse pregnancy outcomes [49,69]. In normal

pregnancies, a lowGIdiet will resultin a reduced rate

ofLGAbabies [70,71]. Forwomen with GDM, a lowGI diet can reduce the rate of insulin use, with no

compromise ofobstetric and fetal outcomes [72].

4.3.2.2Exercise

A moderate amount of exercise is beneficial for most

people most of the time, and pregnancy is no

exception.The expert opinion of ACOG was that a

minimum of 30 minutes exercise on most days of theweek was recommended during a normal pregnancy[73]. There is no indication that this opinion, withcommon sense precautions, would be anydifferent for

pregnant women with diabetes.Women who wereexercisingbefore pregnancy should be encouraged to

continue this during the pregnancy though the extentand type of exercise may need to be modified. For

women with GDM, exercise can be seen as a usefuladjunct to treatment [3,64,74]. Exercises that effectivelyavoid excessive abdominal muscular contraction arepreferred [59].

Women who exercise regularly are probably less

likely to develop GDM, although this reduced rate

appears to be related to the habitual amount of

exercise rather than exercise started in the year beforethe pregnancy [75]. An exercise programme may bean alternative to the use of insulin in women with

GDM who have not

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responded to diet alone [76,77]. This may come aboutdue to the increased insulin sensitivity associated with

exercise therapy [78,79].

Advice on exercise should be tailored to the previous

exercise habits of the individual.Ifthey were previouslysedentary, then arm exercises may be a good starting

point. Inactivity can be expected to result in a furtherreduction in insulin sensitivity.

In summary, exercise may be useful for preventingGDM and also for improving insulin sensitivity. This

is based on limited and diverse clinical studies as wellas expert opinion.The prescription of exercise duringpregnancy is hindered by lackofevidenceregarding thetype,frequency and intensity [80].

4.3.3 Insulin use duringpregnancy

Insulin has been used in pregnancy since 1922. It is es-

sentialforwomen with type 1 diabetes and is stillwidely

considered the drug of choice for women with either

type 2 diabetes orGDM who are not meetingtreatment

goals with lifestyle modification and/or oral glucose-lowering agents. The clinical experience with insulinuse is vast,but the availabil ityofclinical trialevidenceis

limited.Thelongeran insulin has been used, the greateris the collective clinical experience but not necessarily

the clinical trialevidence.Highly purifiedanimal insulinshave been largely replaced by human insulinpreparations. These in turn are now being replaced in

some marketsby insulin analogues,modified to produceeithera more

rapid action for mealtime use or a longerduration ofaction for basal use.

Human insulin was shown to achieve improvedpregnancy and infant outcomes compared with highlypurifiedanimal insulins [81]. Commencing in 1999, the

safety and efficacy of the rapid-acting analogue insulinlispro has been demonstrated in pregnancy in pre-existing diabetes and GDM [82,83], and it was found not

to cross the placenta [84].The second rapid-actinganalogue, insulin aspart, has also been shown to be safeand effective in pregnancy in type 1 diabetes [85,86]and GDM [87]. The use ofthese two analogues has been

the subject of a systematic review [88].There arecurrently no data regarding the rapid-acting analogue

insulinglulisinein pregnancy.

For the long-acting insulin analogues, there is limitedexperience inpregnancy with insulin glargine[89-92]butno data so farforinsulin detemir, although a trial is now

under way.

The decision about which type of insulin and which

insulin regimen to start or continue during pregnancyshould be taken after informed discussion.The more

limited clinical experience and therefore thetheoretical possibil ity of as yet unknown risksassociated with the newer insulin analogues needs to bebalancedagainstpatientpreference and overall glycaemic

control and stability.

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4.3.4 Oral glucose-lowering agentsin pregnancy

4.3.4.1 Generalconsiderations

The majority of women diagnosed with GDM can be

managed by modification of lifestyle (includingpatternsof eating and of physical activity).However, women who

exceed predetermined glycaemic goals have been gener-

ally advised to commence on insulin. Insulin is

expensive, relatively difficult to administer, and alsodifficult to store if the circumstances are less thanoptimal. In recent years two clinicaltrials have examinedthe effects of the use during pregnancy of glyburide

(glibenclamide) [93] and metformin [94].These studieshave stimulated the debate about the use of oral

glucose-lowering agents for the treatment of womenwith GDM.

Glucose profiles in women with GDM will show a basal

level and postprandial spikes.When considering the

glucose crossing from the mother to the fetus, there isa basal consistent amount and the spikes associated

with food intake. On a theoretical level, in the process

of transferof the higher postprandial glucose levels, thefetus wil l tend to recirculate the higher glucose viaamniotic fluid reuptake, thusproducing a more profoundand prolonged effect than the simpler rise and fall of

glucose seen in the mother[95]. Thus agents that lowerthe maternal basal glucose level may not have as great

an effect on the fetus as agents that lower the maternalpostprandial glucose levels. This concept should be kept

in mind when thera - peutic choices are beingconsidered.

4.3.4.2Metformin

There has been extensive clinical experience with theuse of metformin in pregnancy over more than a quarterof a century [96,97]. Metformin does cross the placenta,but there appear to have been no teratogenic problems,

although this question has not been systematicallyexam-ined.The recent Metforminin GestationalDiabetes(MiG)

study [94] has shown that metformin can be a viable

alternative to insulinin a proportion ofcases. BothNICEand CDA include metformin as an option fortreatmentof GDM, and NICE also includes metformin as an

option forthe treatment of type 2 diabetesinpregnancy,with the proviso that it is not licensed for these

indications [2,3].

4.3.4.3Sulfonylureas

Not all sulfonylureas cross the placenta, and the use of

glibenclamide(glyburide) to treat women with GDM wasexamined prospectively by Langer[93] and has subse-quently been the subjectofseveralretrospectivereports,as recently reviewed [98].As with metformin,

glibenclamide (glyburide) appears to be an alternative toinsulin in some instances, although dose titration can

mean that women may be without optimal treatment for

some weeks. Both NICE and CDA includeglibenclamide (glyburide) as an option fortreatment of

GDM (although it is not licensed for this indication)

[2,3]. However, despite these positives, forwomen with

type 2 diabetes there have been some reports of

adverse outcomes associated with the use ofglibenclamide(glyburide) in the third trimester [97,99].

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4.3.4.4 Otheragents

Insulin secretagogues ofthe meglitinideclassmightappear

to offertheoreticaladvantages in controll ingpostprandialglucose levels but have not been subject to eitherhistorical usage orprospectivestudies.The-glucosidase

inhibitors, especially the non-absorbable acarbose, also

offer theoretical postprandial advantages and are being examined. The insulin sensitizers of thethiazolidinedione class are contra-indicated inpregnancy.

4.3.4.5 Combinationtherapy

In the MiG study women taking metformin who had

insulin added were found to require a lower dose ofinsulin [94]. However, the use ofmetforminwith insulinormetformin withglibenclamide(glyburide) has not beensystematically examined in pregnancy.

4.3.4.6 Fetalmalformations

Women with type 2 diabetes or women treated forpoly-cystic ovary disease may be taking oral glucose-

lowering agents at the time of conception. Afteradjusting for the effects of less than optimal glycaemiccontrol, there does not appear to be any increase in therate of fetal malforma- tion [100,101]. Clearly a

discussionofrisks and the option ofalternative therapy isneeded at the earliestopportunity.

4.3.4.7

Conclusion

The clinical experience with insulin therapy is vast andwith- out problem and it remains the agent of choice

wheneverpossible.Therealso does not appear to be anyclearharm with respect to pregnancy outcomes from

using either


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metformin or glibenclamide (glyburide). The long-termeffects of these agents on the developing child have not beensystematically examined, but this observation also applies toinsulinin general, letalone the different types of insulin.Many

countriesalso have regulatoryrequirements or non-approvalof certain agents in pregnancy.

For women with GDM, who exceed predetermined glycaemic

goals, insulin is the preferred treatment. However, ifallowable, metformin and glibenclamide(glyburide) can be

considered safe and effective alternatives in manyinstances. In poorly resourced areas of the world, the

theoretical disadvantages of using oral glucose-loweringagents forwomen withGDM and type 2 diabetes are far

less than the risks of non-treatment. Where insulincannot be afforded, or where circumstances make itsusehazardous, then oralagents canbe the only option.

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5. After pregnancy5.1Breastfeeding

Unless there is a specific contra-indication or concern,breastfeeding is the preferred option foral l women.This

general recommendation is also applicable to womenwhose pregnancy was affected bypre-existing or ges-tational diabetes. However, it should be noted that it is

possible forbreastfeeding to have an influence on mater-nal glycaemic control, and maternal diabetes may in turninfluence the composition of breast milk.

Along with nutritional and immunological advantages,

breastfeeding has been associatedin the generalpopula-tion with a reduction in the rates ofchildhood obesity.

The breast milk of mothers with diabetes has beenshown to have a higher glucose and energy contentthan that of non-diabetic mothers [102,103]. Perhaps

because of this, the potential forbreastfeeding to be

protec- tive against subsequent overweight in thechildren ofwomen with diabetes has been questioned,and this has been examined without clearconclusionsbeing drawn [104]. In the absence ofevidence,it seemsadvisable to maintain good maternal glycaemic controlduring thebreastfeeding period.

For women with pre-existing insulin-treated diabetes, in

limited studies, there was no difference in insulinrequirements or in the rate of hypoglycaemiabetween those women who breastfed compared with

those women who did not [105,106]. However, there isrecent evidence that

type 1 diabetic women have a reduced basal insulin

need during lactation [107].

Transfer of metformin to human mi lk is minimal, at


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I ffurther pregnancies are planned, then a repeat OGTT prior to conception or at least in the first trimester is

desirable.I fno abnormalityispresent, then testingshouldbe repeated at the usual time and with the usual indica-tions during pregnancy.

If no furtherpregnancies are planned, the long-termfollow-up arrangements will depend heavily on the per-ceivedriskofdeveloping type 2 diabetes.In a high-riskgroup there should be an annual OGTT. In a low-riskgroup there could be fastingglucose every two to three

years and an OGTT only if this level is 5.5 mmol/l(100 mg/dl).

5.3 Prevention of type 2 diabetes in

women who developed GDMWomen with previous GDM are at very high risk ofdeveloping type 2 diabetes [113].The rate ofconversionwill depend on a mixture of community and genetic

factors. The prevention, or at leastdelay in the devel-opment, of type 2 diabetes is an attractive option,

as it is likely to reduce the risks associated withhaving establisheddiabetes.

There are several diabetes prevention studies, all with

positive outcomes. Two studies have targeted women

with previous GDM. The first was the Troglitazone

in Prevention of Diabetes (TRIPOD) study thatexclusively enrolled women with previous GDM and

showed a 55%

riskreductionin the troglitazone treated group comparedwith placebo [114].This beneficial effect was

substantiated in the follow-on Pioglitazone inPrevention of Diabetes (PIPOD) study when

pioglitazone was substituted [115].

The second study was the Diabetes Prevention Program(DPP), where women with previous GDM wereincluded [116].This study demonstrated a significantreduction in type 2 diabetes for both lifestylemodification and metformin therapy compared with

placebo. A subsequent sub-group analysis of the resultsfound that, for women with previous GDM, lifestyle

modification and metformin were equally effective[117].

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6. Recommendations for Standard CareThese recommendationsonly address areas of pregnancy care commonlyaffected bythe co-existence of diabetes, and not routine obstetric care such as fetal scanning andmonitoring.

Pre-pregnancycounsellingForal l fertile women ofchild-bearingage with diabetes, identify possibilityof

pregnancy by direct questioning on every relevant occasion. Provide contraceptiveadvice where appropriate.

Offerappropriate pre-pregnancy advice to all women so identified,especiallywith respect tothyroid status, folicacidsupplementation, and the assessment of

any diabetescomplicationsthat may change during the pregnancy.

Provideeducation on the management ofpregnancy with diabetes,explainingrisks and how they can be minimized.

Advise optimization ofglycaemic control(pre-conception target DCCT-alignedHbA

1c


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Stop ACE inhibitorsandARBs and use appropriatesubstitutes.

Stop statins,fibrates and niacin.

Assess establisheddiabetescomplications,especiallyofthe eyes and kidneys;discuss and manage identified problems.

At first prenatal visitFor women with diabetes who have had pre-pregnancy counselling,reviewunderstanding of management of diabetes inpregnancy, current drug therapy,

blood glucose control, diabetescomplications, and presence of other medicalconditions. Advise as appropriate.

For women with diabetes who may have missed pre-pregnancy counselling,determineHbA

1cas soon as practical, and offeradvice on riskon the basisofthe result.

For women who are at high riskofdiabetes because ofpreviousGDM, providehealthylifestyleadvice and offeran OGTT as soon as practical.Ifthe resultisnormal, then offeragain at 26 to 28 weeks ofgestation.A one-stage definitive

procedure ispreferred.

Forall other women (unless a selective process based on riskfactorsisdeemed moreappropriate),advise that they will be offeredtestingforGDM at26 to 28 weeks ofgestation.

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Frequency of subsequent visitsVisitsshould be as frequently as required,depending on achievementofglycaemic targets and management ofother diabetes-associated orobstetric

problems.This may be monthlyin the first two trimesters and more frequentlythereafter.

Ongoing management of diabetes during pregnancyLifestyle management

Offernutritional management and education.Adviceshould be individualized andculturallysensitive, and should be administered by a healthcare professional,ideally someone with specificexpertisein medical nutrition therapy (MNT).

Offergeneralinstruction about nutrition and specificadvice about carbohydrateintake,which wherever possibleshouldincludefoodswith a lowglycaemicindex.If insulin is being used, then the choice, quantity and distribution of carbohydratewill need to becoordinatedwith the amount, type and distribution of the varyinginsulin requirementsofpregnancy.

Encourage physical activity, tailoringadvice to the previousexercise habits of

the individual.Explain that exercise can counter the declinein insulin sensitivitythat occurs during pregnancy and that restingwill have the oppositeeffect.

Glucose control

Use HbA1c

as an ancillaryaid to self-monitoring.Aimforan HbA1c


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Ifat all possible,self-monitoringofbloodglucose(SMBG) should be donefrequently. Forwomen with pre-existingdiabetesthiswillrelate to theirprevious

pattern oftesting and the type ofinsulin regimen they are using.

Adjust the dose oforalglucose-lowering agents or insulin on the basisofself-monitoringresults, HbA

1cand experienceofhypoglycaemia, and be

prepared to changefromoralglucose-lowering agents to insulin ifrequired.

Other diabetes-associated problems

Examine eyes at first prenatalvisit and each trimester.

Monitorblood pressure and advise/treataccordingly,avoiding ACE inhibitorsand ARBs.

Management of gestational diabetesAdvise on risksofadverse pregnancy outcome and how these may be reduced.

Instructin self-monitoringofbloodglucose (to be used fourtimesdaily, fasting and1 h aftereach meal), and advise on lifestylemodification.

Ifagreed glucosecontrol targets are not met within 1 to 2 weeks ofinitiation of

lifestyle management, offerglucose-loweringmedication.Insulin has been, and islikely to remain, the treatment ofchoice but there is now adequate evidence toconsiderthe use ofmetformin and glibenclamide(glyburide) as treatment optionsforwomen who have been informedofthe possiblerisks.Combination therapy hasnot been specifically studied.

Do not use routine measurement ofHbA1c

formanagement.

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After deliveryAnticipatechanged insulinrequirements(immediatereduction), and thus the need formore frequentglucosemonitoring,ifcontinuinginsulin postpartum and during

breastfeeding.

For women who developedGDM, stop glucose-lowering therapy.At

discharge, reinforcelifestyle management advice.

BreastfeedingEncourage breastfeeding(nutritional and immunological benefits to thebaby).Advise women with type 1 diabetes or type 2 diabetes that self-monitoringshouldcontinue

and good glycaemic controlshould be maintainedduringthis period.

Insulin requirements drop immediatelyafterdelivery, and a dose adjustmentwillbe needed toallowforthe eating patterns ofthe breastfeedingmother.

Review medications, taking into consideration the potential risks associated withany transfer into the milk.Metformin andpossibly glibenclamide(glyburide) may beused. Statins should be avoided, and consideration should be given to the choice

of anti-hypertensive agents.

Follow-up within 6 weeksAt a convenienttime,from 0 to 6 weeks afterpregnancy,ideally togetherwithotherpostpartumassessments, checkfordiabetesin women who developedGDM.Ifthen

non-diabetic,advise on high riskoffuturediabetes and onpreventativelifestyle

measures. Advise checkfordiabetes every one to three years. Iffurtherpregnanciesareplanned, advise on the riskofdeveloping GDM again, and the need forpre-pregnancy counsell ing.

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7. ImplementationImplementation of these recommendations will requireliaison between healthcare professionals involved india- betes, obstetric and neonatal care, such that joint

proto- cols can be devised for pregnancy and post-pregnancy management.Localdecisionswillbe required

as to means of testing forGDM and whether a selectiveor universal approach willbe used.

Healthcare professionals will need to be trained on preg-

nancy-specific lifestyle adaptation, insulin use, screening

for complications.Availability of such staff needs to beassured. Self-monitoring equipment and insulin supply

need to be as- sured. Laboratory resources should beprovided for clinical monitoring of glucose control and

assessment of renal damage. Pre-pregnancy services mayneed tobeorganizedseparately.

8. EvaluationDelivery weight of the infant and achieved maternalHbA

1c

each trimester may be useful surrogate outcomesfor

quality assurance. Structural review should be of theexist- ence ofjoint management protocolsaddressing theabove recommendations, and appropriate availabilityofstaff.

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9. References1. IDF Clinical Guidelines Task Force. Global

Guideline for Type 2 diabetes. Brussels:International Diabetes Federation, 2005.

2. National Collaborating Centre forWomens and

Childrens Health. Diabetes inpregnancy. Revisedreprint July2008. London: RCOG Press.(ww w .nice. org.uk)

3. Canadian Diabetes Association Clinical PracticeGuidelines Expert Committee. Canadian DiabetesAssociation 2008 clinicalpractice guidelines fortheprevention and management of diabetes in Canada.

Can J Diabetes 2008; 32 (Suppl1): S168-S180.

4. The HAPO Study Cooperative Research Group.

Hyperglycemia and adverse pregnancy outcomes.N Engl J Med2008; 358: 1991-2002.

5. American Diabetes Association. Diagnosis and

classificationof diabetes mellitus (positionstatement). Diabetes Care 2009; 32 (Suppl

1): S62-S67.

6. Tallarigo L,Giampietro O, Penno G, et al. Relationof glucose tolerance to complications of pregnancy

in nondiabetic women. N Engl J Med1986; 315:

989-92.

7. Berkus MD, Langer O. Glucose tolerance test:degree of glucose abnormality correlates with

neonatal outcome. Obstet Gynecol 1993; 81:344-8.

8. Moses RG, Calvert D. Pregnancy outcomes inwomen without gestational diabetes mellitus relatedto the maternal glucose level. Is there a continuum

ofrisk? Diabetes Care 1995; 18: 1527-33.

9. Sacks DA, Greenspoon JS ,Abu-FadilS, etal.Toward universal criteria forgestational

diabetes; the75-gram glucose tolerance test inpregnancy.Am

J Obstet Gynecol 1995; 172: 607-14.

10. Weiss PAM,HaeuslerM,Tamussino K, et al. Canglucose tolerance test predict fetal hyperinsulinism?

BJOG 2000; 107: 1480-5.

11. JensenDM, Korsholm L, Ovesen P, et al.Adversepregnancy outcome in women with mild glucose

intolerance: is there a clinically meaningfulthresholdvalue forglucose?Acta Obstet Gynecol

Scand2008;87: 59-62.

12. Beischer NA,Wein P, Sheedy MT, et al.Identification and treatment of women withhyperglycaemia diagnosed during pregnancy can

significantly reduceperinatal mortality rates.Aust

NZ J Obstet Gynaecol

1996; 36: 239-47.

13. SchmidtM I,Duncan BB,Reichelt AJ,et al.Gestational diabetes mellitus diagnosed with a

2-h 75-g oral glucose tolerance test and adversepregnancy outcomes. Diabetes Care 2001; 24:

1151-5.

24
http://www.nice/http://www.nice/


44/62



45/62


14. Drexel H, Bichler A, Sailer S, et al. Prevention ofperinatal morbidity by tight metabolic control in

gestational diabetes mellitus.Diabetes Care

1988; 11:761-8.

15. Langer O, Rodriguez DA, Xenakis EMJ,et al.

Intensified versus conventional management ofgestational diabetes.Am J Obstet Gynecol

1994; 170:1036-47.

16. LangerO,Yogev Y, Most O, et al. Gestationaldiabetes:The consequences of not treating.Am

J Obstet Gynecol 2005; 192: 989-97.

17. Crowther CA, HillerJ E ,Moss JR ,et al., fortheAustralianCarbohydrate IntoleranceStudy inPregnant Women (ACHOIS)Trial Group.E ffect of treatment ofgestationaldiabetes

mellitusonpregnancy outcomes. N Engl J Med2005; 352:2477-86.

18. Landon MB,ShriverEKforthe MFMU. A

prospective multicenter randomized treatment trialof mild gestational diabetes (GDM) (abstract).Am

J Obstet Gynecol 2009; 199(6) (SupplA): S2.

19. Pettitt DJ, AleckKA, Baird HR, et al. Congenital

susceptibility to NIDDM.Role of the intrauterine

environment. Diabetes 1988; 37: 622-8.

20. Silverman BL,MetzgerBE,Cho NH, et al. Impaired

glucose tolerance in adolescent offspringof diabeticmothers. Relationship to fetal hyperinsulinism.

Diabetes Care 1995; 18: 611-7.

21. Sobngwi E, Boudou P, Mauvais-Jarvis F, et al. Effectof a diabetic environment in utero on

predisposition

to type 2 diabetes. Lancet2003; 361: 1861-5.

22. Franks PW, Looker HC, Kobes S,et al.Gestational glucose tolerance and risk of type 2

diabetes inyoung Pima Indian offspring.Diabetes 2006; 55: 460-5.

23. Hillier TA, Pedula KL,Schmidt MM,et al.Childhood obesity and metabolic imprinting.Theongoing effects of maternal hyperglycemia.Diabetes Care

2007; 30: 2287-92.

24. Clausen TD, Mathiesen ER ,Hansen T, et al. Highprevalence of type 2 diabetes and pre-diabetes inadult offspringof women with gestational diabetesmellitus or type 1 diabetes.The role ofintrauterinehyperglycemia.Diabetes Care 2008; 31: 340-6.

25. Kim C, BergerDK, Chamany S. Recurrence ofgestational diabetes mellitus:a systematic review.

Diabetes Care 2007; 30: 1314-9.

26. Cooper WO, Hernandez-Diaz S, Arbogast PG, et al.

Major congenital malformations afterfirst-trimesterexposure to ACE inhibitors. N Engl J Med2006;

354:2443-51.

27. Hod M,van Dijk DJ,Weintraub N, et al. Diabeticnephropathy andpregnancy: the effect ofACE

inhibitors prior to pregnancy on fetomaternaloutcome. Nephrol Dial Transplant1995; 10:

2328-33.

25


46/62




47/62


28. BarJ ,Chen R, Schoenfeld A, et al. Pregnancyoutcome in patients with insulin dependentdiabetes mellitus and diabetic nephropathy treatedwith ACE inhibitors before pregnancy.J Pediatr

Endocrinol Metab 1999; 12: 659-65.

29. Joint Formulary Committee. British National

Formulary. 57th

edn. London: British MedicalAssociation and Royal Pharmaceutical Society ofGreat Britain, 2009.(ww w .bnf.org)

30. Janz NK, Herman WH, BeckerMP, et al. Diabetesandpregnancy: factors associated with seekingpre-conception care. Diabetes Care 1995; 18: 157-

65.

31. Key TC, GiuffridaR,Moore TR. Predictive valueof early pregnancy glycohemoglobin in theinsulin- treated diabetic patient.Am J Obstet

Gynecol 1987;156: 1096-100.

32. MillsJL ,Simpson J L ,Driscoll SG, et al. Incidence

of spontaneous abortion among normal womenand insulin-dependent diabetic women whose

pregnancies were identified within 21 days ofconception. N Engl J Med1988; 319: 1617-23.

33. Rosenn B, MiodovnikM,Combs CA, et al. Pre-conception management of insulin-dependentdiabetes: improvement of pregnancy outcome.

Obstet Gynecol 1991; 77: 846-9.

34. Greene MF, Hare JW, Cloherty JP, et al. First-trimester hemoglobin A1 and riskformajormalformation and spontaneous abortion in diabetic

pregnancy. Teratology1989; 39: 225-31.

35. Suhonen L,HiilesmaaV,Teramo K.Glycaemic control during early pregnancy

and fetal malformations in women with type Idiabetes mellitus.Diabetologia 2000; 43:

79-82.

36. Diabetes and Pregnancy Group France. Frenchmulticentric survey of outcome of pregnancy inwomen with pregestational diabetes. Diabetes

Care

2003; 26: 2990-3.

37. Fuhrmann K, Reiher H, SemmlerK, et al.

Prevention of congenital malformations in infants of

insulin- dependent diabetic mothers. Diabetes

Care 1983; 6:219-23.

38. JensenDM, Korsholm L, Ovesen P, et al. Peri-conceptional A1C and risk of serious adverse

pregnancy outcome in 933 women with type 1diabetes. Diabetes Care 2009; 32: 1046-8.

39. Nathan D, Kuenen J ,Borg R, et al.Translating theA1C assay into estimated average glucose

values. Diabetes Care 2008; 31: 1473-8.

40. Griffin M E, Coffey M , Johnson H, et al. Universal

vs. risk factor-based screening for gestational

diabetes mellitus: detection rates, gestation atdiagnosis and outcome. Diabet Med 2000; 17:

26-32.

26
http://www.bnf.org/http://www.bnf.org/http://www.bnf.org/


48/62




49/62


41. Moses RG, Grif fithsR, Davis W. Gestationaldiabetes. Do al l women need to be tested?Aust

NZ J Obstet Gynaecol 1995; 35: 387-9.

42. Coustan DR,Nelson C, Carpenter MW, et al.

Maternal age and screening forgestational diabetes:

A population-based study. Obstet Gynecol 1989;

73:557-61.

43. WilliamsCB, Iqbal S, Zawacki CM, et al. Effect ofselective screening forgestational diabetes.

Diabetes Care 1999; 22: 418-21.

44. Naylor CD, Sermer M,Chen E,Farine D, fortheToronto Trihospital Gestational Diabetes Project

Investigators. Selective screening forgestationaldiabetes mellitus.N Engl J Med1997; 337:

1591-6.

45. Greene MF. Screening forgestational diabetesmellitus (editorial). N Engl J Med1997; 337:

1625-6.

46. Simmons D, Devers MC,Wolmarans L,et al.

Difficulties in the use of risk factors to screen forgestational diabetes mellitus (letter). Diabetes

Care

2009; 32: e8.

47. Landon MB,Gabbe SG, Piana R, et al.Neonatalmorbidity in pregnancy complicated by diabetesmellitus:predictive value of maternal glycemic

profiles.Am J Obstet Gynecol 1987; 156:

1089-95.

48. InksterME,Fahey TP, Donnan PT, et al. Poorglycated haemoglobin control and adversepregnancy outcomes in type 1 and type 2 diabetes

mellitus: Systematic review of observational studies.

BMC Pregnancy and Childbirth 2006; 6: 30.

49. de Veciana M,MajorCA, Morgan MA, et al.

Postprandial versus preprandial blood glucosemonitoring in women with gestational diabetesmellitus requiring insulin therapy. N Engl J Med

1995;333: 1237-41.

50. Manderson JG ,Patterson CC, Hadden DR, et al.

Preprandial versus postprandial blood glucose

monitoring in type 1 diabeticpregnancy: arandomized controlled clinicaltrial.Am J

Obstet Gynecol 2003; 189: 507-12.

51. Moses RG, Lucas EM,Knights S. Gestationaldiabetes mellitus.At what time should the

postprandial glucose level be monitored?Aust

NZ J Obstet Gynaecol 1999; 39: 458-60.

52. Sivan E,Weisz B,Homko CJ,et al. One or two

hours postprandial glucose measurements: are theythe same?Am J Obstet Gynecol 2001; 185:

604-7.

53. Parretti E,MecacciF, Papini M,et al.Third-trimester maternal glucose levels from diurnal

profilesin nondiabeticpregnancies: correlation withsonographic parameters offetal growth.Diabetes Care 2001; 24: 1319-23.

54. BerkMA,Mimouni F, MiodovnikM,et al.

Macrosomia in infants of insulin-dependent diabeticmothers. Pediatrics 1989; 83: 1029-34.

27


50/62

27




51/62

g y

55. Evers IM ,De ValkHW, Mol BWJ,et al.Macrosomia despite good glycaemic control inType I diabeticpregnancy; results of a nationwide

study in TheNetherlands. Diabetologia 2002;

45: 1484-9.

56. JovanovicL,Druzin M,Peterson CM. Effect ofeuglycemia on the outcome of pregnancy ininsulin- dependent diabetic women as compared

with normal control subjects. Am J Med1981; 71:

921-7.

57. JovanovicL.The role of continuous glucosemonitoring in gestational diabetes mellitus.Diabetes Technol Ther2000; 2 (Suppl1): S67-S71.

58. Yogev Y, Chen R, Ben-Haroush A, et al. Continuousglucose monitoring forthe evaluation of gravid

women with type 1 diabetes mellitus.Obstet

Gynecol

2003; 101: 633-8.

59. MetzgerB E,BuchananTA, Coustan DR, et al.

Summary and recommendations of the Fifth

International Workshop-Conference on GestationalDiabetes Mellitus.Diabetes Care 2007; 30 (Suppl

2): S251-S260.

60. Peterson CM, Jovanovic-Peterson L.Percentage ofcarbohydrate and glycemic response to breakfast,lunch,and dinner in women with gestationaldiabetes. Diabetes 1991; 40 (Suppl 2):172-4.

61. Jovanovic-Peterson L, Peterson CM.Nutritionalmanagement of the obese gestational diabetic

pregnant woman (guest editorial).J Am Coll

Nutr

1992; 11: 246-50.

62. Stothard KJ,Tennant PWG, BellR,et al. Maternal

overweight and obesity and the risk of congenitalanomalies: A systematic review and meta-analysis.JAMA 2009; 301: 636-50.

63. Oddy WH, De Klerk NH, MillerM,et al.Association of maternal pre-pregnancy weight with

birthdefects: Evidencefrom a case-control study in

Western Australia.Aust NZ J Obstet Gynaecol 2009;

49: 11-5.

64. American Diabetes Association. Gestationaldiabetes mellitus (position statement). Diabetes Care2004; 27 (Suppl1): S88-S90.

65. Magee MS,Knopp RH, Benedetti TJ .Metaboliceffects of 1200-kcal diet in obese pregnant womenwith gestational diabetes. Diabetes 1990; 39: 234-

40.

66. Rae A, Bond D, EvansS, et al. A randomisedcontrolled trial of dietary energy restriction in themanagement of obese women with gestational

diabetes.Aust NZ J Obstet Gynaecol 2000; 40:

416-22.

67. JovanovicL.Time to reassess the optimal dietaryprescription forwomen with gestational diabetes.

Am J Clin Nutr1999; 70: 3-4.

68. SheardNF, Clark NG, Brand-MillerJC, et al.Dietary carbohydrate (amount and type) in the

prevention and management of diabetes. A

statement by the American Diabetes Association.Diabetes Care 2004;27: 2266-71.

28


52/62




53/62

69. Jovanovic-Peterson L,Peterson CM, Reed GF, et al.,the National Institute of Child Health and HumanDevelopment Diabetes in Early Pregnancy Study.

Maternal postprandial glucose levels and infantbirth weight: the Diabetes in Early Pregnancy Study.

Am J Obstet Gynecol 1991; 164: 103-11.

70. Clapp JE .Diet, exercise, and feto-placentalgrowth.

Arch Gynecol Obstet1997; 261: 101-7.

71. Moses RG, Luebcke M, Davis WS, et al.The effectof a low-glycemic-index diet during pregnancy onobstetric outcomes.Am J Clin Nutr2006; 84:

807-12.

72. Moses RG, Barker M,Winter M,et al. Can a lowglycemic index diet reduce the need forinsulin ingestational diabetes mellitus?A randomized trial.

Diabetes Care 2009; 32: 996-1000.

73. ACOG Committee of Obstetric Practice .ACOGCommittee Opinion, No. 267, January 2002:exercise during pregnancy and the postpartumperiod. Obstet Gynecol 2002; 99: 171-3.

74. American College of Obstetricians andGynecologists. Gestational diabetes.ACOGPractice Bulletin 2001; 30: 525-38.

75. Gavard JA ,Artal R. Effect of exercise on pregnancy

outcome. Clinical Obstetrics and

Gynecology2008; 51:467-80.

76. Jovanovic-Peterson L,DurakEP, Peterson

CM. Randomized trial of diet versus diet pluscardiovascular conditioning on glucose levels in

gestational diabetes.Am J Obstet Gynecol

1989; 161:415-9.

77. Bung P, Artal R, KhodiguianN, et al. Exercisein gestational diabetes: an optional therapeuticapproach? Diabetes 1991; 40 (Suppl2): 182-

5.

78. BungP, BungC, Artal R, et al.Therapeuticexercise forinsulin-requiring gestational diabetics:effectson the fetus results of a randomizedprospective

longitudinalstudy.J Perinat Med1993; 21: 125-37.

79. Garcia-Patterson A, Martin E,Ubeda J ,et al.

Evaluation oflight exercise in the treatment ofgestational diabetes (letter). Diabetes Care

2001; 24:2006-7.

80. Jovanovic-Peterson L,Peterson CM. Is exercisesafe or useful forgestational diabetic women?Diabetes

1991; 40 (Suppl2): 179-81.

81. Jovanovic-Peterson L,KitzmillerJL, Peterson CM.

Randomizedtrialofhuman versus animal species

insulin in diabetic pregnant women:improvedglycemic control, not fewerantibodies to insulin,

influencesbirth weight.Am J Obstet Gynecol 1992; 167: 1325-30.

82. Bhattacharyya A, Brown S,Hughes S, et al.Insulin lispro and regularinsulin inpregnancy. Q

J Med 2001; 94: 255-60.


54/62

29




55/62

83. Wyatt JW, Frias JL ,Hoyme HE, et al. Congenitalanomaly rate in offspringof mothers with diabetestreated with insulin lispro duringpregnancy.Diabet Med2005; 22: 803-7.

84. JovanovicL, Ilic S, Pettitt DJ, et al. Metabolic andimmunologic effects ofinsulin lispro in gestationaldiabetes. Diabetes Care 1999; 22: 1422-7.

85. Mathiesen ER,Kinsley B,AmielSA,et al.Maternal glycemic control and hypoglycemia intype 1 diabeticpregnancy: a randomized trial ofinsulin aspart versus human insulin in 322

pregnant women. Diabetes Care 2007; 30:

771-6.

86. Hod M ,Damm P, KaajaR, et al. Fetal andperinatal outcomes in type 1 diabetespregnancy:

a randomized study comparing insulin aspart with

human insulin in 322 subjects.Am J Obstet

Gynecol

2008; 198 (2): 186.e1186.e7.

87. Pettitt D, Ospina P, Howard C, et al. Efficacy, safetyand lack ofimmunogenicity ofinsulin aspart

compared with regular human insulin forwomenwith gestational diabetes mellitus.Diabet Med

2007;24: 1129-35.

88. PlankJ ,SiebenhoferA, BergholdA, et al.Systematic review and meta-analysis of short-

acting insulin analogues in patients with diabetesmellitus.Arch Intern Med2005; 165: 1337-44.

89. Pyhnen-Alho M, Rnnemaa T, Saltevo J ,et al.Use ofinsulinglargineduringpregnancy.ActaObstet Gynecol Scand2007 Aug 29: 1-4.

90. Price N, Bartlett C, Gillmer MD. Use ofinsulin glargine during pregnancy: a casecontrol pilot study. BJOG 2007; 114: 453-7.

91. Di Cianni G,Torlone E,Lencione C. Perinataloutcomes associated with the use ofglargine in

pregnancy. Diabet Med2008; 25: 993-6.

92. Gallen IW,Jaap AJ,Roland JM ,et al. Survey ofglargine use in 115 pregnant women with type 1diabetes. Diabet Med2008; 25; 165-9.

93. Langer O, Conway DL, Berkus MD, et al. A

comparison ofglyburide and insulin in women withgestational diabetes mellitus.N Engl J Med2000;343: 1134-8.

94. Rowan JA ,Hague WM, Gao W, et al.Metformin versus insulin forthe treatment of

gestational diabetes. N Engl J Med2008; 358:

2003-15.

95. JovanovicL. Point: Oral hypoglycemicagents shouldnot be used to treat diabetic pregnant women.Diabetes Care 2007; 30: 2976-9.

96. Coetzee E J ,JacksonWPU. Metformin in themanagement of pregnant insulin-independent

diabetics. Diabetologia 1979; 16: 241-5.

30


56/62




57/62

97. Coetzee E J ,JacksonWPU.The management ofnon-insulin-dependent diabetes during

pregnancy. Diabetes Res Clin Pract1986; 1:

281-7.

98. Moore T. Glyburide forthe treatment of

gestational diabetes. Diabetes Care 2007; 30

(Suppl 2):S209-S213.

99. EkpebeghCO, Coetzee E J ,van der Merwe, et al.

A 10-year retrospective analysis of pregnancyoutcome in pregestational Type 2 diabetes:comparison ofinsulin and oral glucose-lowering

agents. Diabet Med2007; 24: 253-8.

100.Towner D, Kjos SL, Leung B, et al.Congenital malformations in pregnancies

complicated by NIDDM. Diabetes Care

1995; 18: 1446-51.

101. Gilbert C,Valois M, Koren G. Pregnancyoutcome after first-trimester exposure tometformin: a meta-analysis.Fertil Steril 2006;

86: 658-63.

102. ButteNF, Garza C, BurrR, et al. Milkcomposition of insulin-dependent diabeticwomen.J Paediatr Gastroenterol Nutr1987; 6: 936-41.

103. Jovanovic-Peterson L,Fuhrmann K, Hedden K, etal.

Maternal milkand plasma glucose and insulin

levels: studies in normal and diabetic subjects.JAm Coll Nutr1989; 8: 125-31.

104. Gunderson EP. Breastfeeding after gestational

diabetespregnancy: subsequent obesity and type2 diabetes in women and their offspring.Diabetes

Care 2007; 30 (Suppl2): S161-S168.

105. Ferris AM,Dalidowitz CK, Ingardia CM, et al.

Lactation outcome in insulin-dependent diabeticwomen.J Am Diet Assoc 1988; 88: 317-22.

106. Saez-de-Ibarra L,GasparR, Obesso A, et al.Glycaemicbehaviour during lactation:postpartum

practical guidelines forwomen with type 1diabetes. Pract Diabetes Int2003; 20: 271-5.

107. RivielloC, MelloG, JovanovicL. Breastfeedingand the basal insulin requirement in type 1

diabetic women.Endocr Pract

2009May-Jun;

15(3):187-93.

108. Hale TW, Kristensen JH ,Hackett LP, etal.Transfer of metformin into human milk.Diabetologia 2002;45: 1509-14.

109. GardinerS J ,KirkpatrickCM, Begg EJ ,et

al.Transfer of metformin into human milk.ClinPharmacol Ther2003; 73: 71-7.

110. BriggsGG, Freeman RK,Yaffe S J .Drugs inPregnancy and Lactation. A Reference Guide

to Fetal and Neonatal Risk.7th edn.Philadelphia: Lippincott,Williams and Wilkins,

2005.

111. Feig DS, BriggsGG, Kraemer JM ,et al.Transfer

ofglyburide and glipizideinto breast milk.Diabetes Care 2005; 28: 1851-5.

31


58/62




59/62

112. American Diabetes Association. Standards ofmedical care in diabetes (position statement).Diabetes Care 2005; 28 (Suppl1): S4-S36.

113. Bellamy L, Casus J ,Hingorani AD,Williams D.Type

2 diabetes mellitus after gestational diabetes: a

systematic review and meta-analysis. Lancet

2009;373: 1773-9.

114. BuchananTA, Xiang AH, Peters RK, et al.

Preservation of pancreatic beta-cell function and

prevention of type 2 diabetes by pharmacologicaltreatment ofinsulin resistance in high-riskHispanic

women. Diabetes 2002; 51: 2796-803.

115. Xiang AH, Peters RK, Kjos SL ,et al. Effect of

pioglitazone on pancreatic beta cell functionand diabetes risk in Hispanic women withpriorgestational diabetes. Diabetes 2006; 55: 517-

22.

116. Diabetes Prevention Program Research Group.

Reduction in the incidence of type 2 diabetes with

lifestyle intervention or metformin. N Engl J

Med2002; 346: 393-403.

117. RatnerRE,Christophi CA, MetzgerBE,et al., forThe Diabetes Prevention Program Research Group.Prevention of diabetes in women with a history

of gestational diabetes: effects of metformin and

lifestyle interventions.J Clin Endocrinol

Metab 2008;93: 4774-9.

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Disclaimer

The International Diabetes Federation (IDF)does not provideindividualizedmedical diagnosis,treatment or advice, nordoes it recommend specific

therapies orprescribe medication foranyone usingor consultingthe GlobalGuideline on Pregnancy and Diabetes. The information contained in thisGuideline is intended and may be used for

general educational and informational purposes only.

Reasonable endeavours have been used to ensure the accuracy of theinformation presented. However, IDF assumes no legalliabilityor responsibility

forthe accuracy, currency orcompleteness of the information provided herein.IDF assumes no responsibility forhow readers use the informationcontainedin this Guideline. Readers, in search of personal medical advice and direction,

should seek advice from and consult with professionally qualifiedmedicalandhealthcare professionalsonspecific situations and conditions ofconcern.



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