2.4 barbour what guidelines to use in gestational diabetes

7/26/2019 2.4 Barbour What Guidelines to Use in Gestational Diabetes

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What Guidelines to

Use in GestationalDiabetes: ACOG or

ADA?

Linda Barbour, MD, MSPH, FACP

Professor of Medicine and Obstetrics and GynecologyDivisions of Endocrinology and Maternal-Fetal MedicineUniversity of Colorado School of MedicineJuly 17, 2014


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Objectives

Why we care so much about diagnosing

and treating GDM Fetal programming of childhood obesity

Why the push-back on adopting the ADAGuidelines? Fetal overgrowth is caused by more than just

glucose; role of obesity, GWG, lipids What is normal glycemia in pregnancy

and at what level to adverse outcomesincrease? Glycemia norms and HAPO trial

ACOG and ADA guidelines for Dx of GDM Reasons for strong ACOG opposition NIH Consensus Panel

Final Thoughts
http://www.time.com/time/magazine/0,9263,7601101004,00.html


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What Is GDM?

Glucose intolerance recognized for the first

time during pregnancy (brought out by the IR of normal pregnancy and demand onbeta cells.

Did not exclude women with pre-existing diabetespreviously undiagnosed

Undiagnosed Type 2 with A1C have risk formajor malformations

Most women diagnosed before 24 weeks haveprediabetes or frank Type 2 DM


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New CDC Estimated Prevalence of GDM ~9.2%June 2014


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Why Do We Care about

Dx and RX of GDM?

Mothers have risk of C-section and preeclampsia

Offspring have LGA, birth trauma, respiratory,cardiac and metabolic disorders

Identifies moms who have 30-50% risk of Type 2DM in 10-20 yrs

Offspring have risk of childhood obesity and DM

2 RCTs show dx and Rx improves some outcomes ACHOIS 2005 using WHO criteria (perinatal mortality)

MFMU 2009 using CC criteria LGA, macrosomia, PEshoulder dystocia
http://images.google.com/imgres?imgurl=www.vertechinc.com/archive/family4/picasso.jpg&imgrefurl=http://www.vertechinc.com/archive/family4/Picasso.htm&h=400&w=286&prev=/images%3Fq%3Dmother%2Bpicasso%26svnum%3D10%26hl%3Den%26lr%3D%26ie%3DUTF-8%26oe%3DUTF-8%26sa%3DN


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PoorNutrition

in Early Life

OrganDevelopment

Changes GeneExpression

Catch UpGrowth

MetabolicSyndrome

Thrifty Phenotype:Hales & Barker (1992)

in Utero

Changes in

GeneExpression

EnvironmentalStimuli,

ContinuedPostnatalGrowth

MetabolicSyndrome

Updated Hypothesis:

Epigenetic Stimuli

Overnutrition

BW and Risk of Childhood Metabolic Syndrome

Developmental Origins Theory-not just GDM


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High birth weight and increased adiposity at age 12 months

increases risk of metabolic syndrome at age 17 yrs old in girls

Obese infants are 2-9 times as likely to be obese as adults Baird J,BMJ 2005;331:929

JCEM, June 2012

Long Term Implications to Offspring


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Increased Neonatal Adiposity inOffspring of GDM

Catalano PM; 2003; Am J Obstet Gynecol; 189:1698

B.W. = 2893 gms;

Body Fat = 16.8% by

DXA


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Newborn IntrahepaticFat Increased in

GDM/Obese OffspringBrumbaugh, Pediatrics 2013

Visceral fat associated with

severe insulin resistance Hepatic fat is associated withNAFLD

N=13 infants of obese GDMand 12 NW mothers

Infants of Obese GDM momshad 68% more intrahepaticfat

Genesis of NAFLD?


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But Maternal Glucose is not theonly Risk Factor for Childhood

Obesity Factors Associated with

high BMI at 2-3 yr:

M ate rna l BM I , LGA , GWG ,G lu cose GDM o r DM ) , L ip ids ,

D ie ta ry fa t

R a te o f I n f an t W e igh t Ga i n

0-6 mo infants triple their fatmass

Rapid wt gain birth-2 yrs; Catch up-growth in IUGR

Feed ing m ode

BF protective in most studies

Poston L. Curr Opin Clin Nutr Metab Care 2012


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Offspring from OW/Obese Moms

Account for Most LGA Births

***Obesity prevalence was 9.3% in 196032% in 2010

Ogden, 2006, JAMA, 295(13): 1549

Flegal, 2012, JAMA, 307(5): 491

Delaney

Buzzell

Big

Enchilada

13 lb 12 oz

Mom

without

GDM


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Why Do Obese Mothers withoutGDM Deliver Big Babies?

Catalano PM 2007;109:419


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Insulin (ng/mL) 4.3 0.4 5.0 0.6 15.9 3.3 14.9 2.0

C-peptide (ng/mL) 1.1 0.05 1.3 0.06 2.6 0.3 2.8 0.2

Tg (mg/dL) 85 5.6 - 152 14.3 -FFA (Eq/L) 366 52 326 29 535 55* 547 58

LEAN: Early Late OBESE: Early Late

Glucoses higher in Obese/non-GDMwomen compared to NW throughout day

and night both early and late in pregnancy

on Controlled Diet by CGM

Diabetes Care 2011 34:2198


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TG early was

strongest

correlate of %

body fat (r=0.67);

FFA late (r=0.54)

Early Maternal

BMI r=0.55

Nothing added

to TG in

regression model

BW not

correlated with

any metabolic

variables

TGs and FFAs Correlate Strongest with Infant Body Fat

Harmon, Gerard, Jensen, Kealey, Hernandez, Reece, Barbour, Bessessen Diabetes Care 2011;34:1


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0

2

4

6

8

10

12

14

16

18

20

-1 19 39 59 79 99 119

%BFDXA2w

k

Delta TG 28_16 , mg/dL

Delta TG 28-16wk vs. %FM DXA 2wks

R=0.6, p


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Maternal Obesity is Much Stronger

Risk for Childhood Obesity than GDM

89 women with GDM or NGT; Offspring evaluated at birth; 6-11 yrs by DXA

No diff in ~ 9 yr old Wt Percentile or % Fat in Offspring of GDM vs NGT

Strongest predictor for offspring % Body Fat at ~9 yrs was Mat BMI >30

(OR=5.5). Explained 18% of variance in childhood adiposity

r=0.3

Catalano PM Am J Clin Nutr 2009;90:1303

CorrelationBetween % FatBirth and Child% Fat


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K im SY Obs te t Gyneco l 2014 ;123 :737

BC data Florida 2004-2008 in

Florida to assess influence of BMI

vs GWG vs GDM on LGA

Excessive GWG

contributed the most to

LGA

Target GWG more than Pre-

Pregnancy BMI or GDM.

Population Attributable Risk to LGA

Gestational Weight Gain ContributesMore to LGA than Overweight or GDM


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GDM Only Part of the Problem:

Predictive Value of BW, Obesity and GDM on

Metabolic Syndrome Age 6-11 Boney CM 2005 Peds 115:e290


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But the Sugar isObviously Important

19 lbs 2oz Baby Boy; Mother

41 with DM

Medan, North Sumatra Indonesia

-12 studies-1975-2008

-N=168-255-33.82.3 wks-BMI 22-28


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Normal Glycemia In Pregnancy

is Lower than RecognizedHernandez T,

Barbour LA et al, Diabetes Care Oct 2011

Current 1-hr target

Current 2-hr target

FBG 721 Hr PP 1092 Hr PP 99


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What Diagnostic Criteria is Used for GDM?ACOG CriteriaPredicts T2 DM, Not Adverse OutcomesPractice Bulletin #137 Aug 2013

Two Step:

50 gm glucose screen non fasting

130-140 cut-off

100 gm OGTT (Carpenter and Coustan)

FBG 95 mg/dl

1 hr 180 mg/dl

2 hr 155 mg/dl

3 hr 140 mg/dl

National Diabetes Data Group FBG 105

1 hr 190; 2 hr 165; 3 hr 135

Used less often; different conversion from whole blood

to plasma from OSullivan criteria)

2 or values diagnosticPred i c ted deve l opmen to f Type 2 DM in m om


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26.3%

5.3%13.3%

27.9%

2.1%

4.6%

3.7%

32.4%

Primary outcomes

1.75

1.75

25,505 women in 15 centers in 9 countries

Objective: Clarify risk of adverse outcome with degreesof maternal glucose intolerance

75 gm 2 hr OGTT; Blinded if FBG


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Diabetes Care 2010;33:676-682

Diabetes Care 2011;34 S62-S69


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DX of GDM and Overt DM per IADPSG

Incidenceof GDM =17.8%

Overt DMdxd byA1C, FBG,or RandomGluc

Used LGArisk by 1.75

above mean(1 abnl value)


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Canadian representative on IADPSG Consensus Panel who did not join

authorshipReproducibility of OGTT poor (25% could be re-classified)

Increased diagnostic rate of 17.8% would prevent only 140 cases LGA and16 cases of birth injury in 23,000 pregnancies

78% LGA infants were not born to GDM mothers; maternal Obesity is astronger predictor of LGA

Rec: Screening with 50 gm and using higher cutoffs on a 75 gm OGTTusing a 2-fold risk of LGA which would give a prevalence of 10.5%

FBG 95 mg/dl or 1 hr 191 OR 2 hr 162 (5.3, 10.6, and 9 mmol/l)


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*Variability in 2 hr OGTT: differing results in ~25% of women ifperformed at different times. 1 step testing may result in more FPs

*Pooled meta-analysis of 5 RCTs: Rx of GDM resulted in BW difference

of


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True Benefits ofRx of Mild GDM?

No difference in obesity risk in 4-5 yr old offspring in ACHOIS Diabetes Care2010;33:964

78% of LGA babies in HAPO no GDM; >90% shoulder dystocia no GDM

ACHOIS; 5 perinatal deaths but 2/5 due to lethal anomaly or IUGR

Rx: BW 140 gm PIH by 6%; IOL, Resp distress, neonatal hypogly

MFMU; N.S. in perinatal mortality or composite outcomes Rx BW 100 gm, PIH by 5%, shoulder dystocia(1.5 vs 4%)

U.S. Preventive Services Task Force and NIH Office of

Medical Applications of Research Ann Intern Med 2013; 159

5 RCTs and 6 Cohort Studies

Women who are treated for GDM have more perinatal visits

Moderate evidence shows PIH, shoulder dystocia, LGA/ Macrosomia;

No diff C-section, IOL, neonatal hypoglycemia, long term infantoutcomes


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Diabetes Care 2010;33:2184-89

The A1C criteria misses 70% of individuals with DM (6.5) and

82-94% with prediabetes (5.7)compared to OGTT data in non-Hispanic White or Black adults

HAPO did not advocate using an A1C of 5.7 to diagnose GDM earlyor proceed with 75 gm testing

Unless a fasting or 75 gm or 2 hr OGTT is performed on high risk

women for GDM in the first trimester, many early cases of GDMand up to 1/3 cases of DM will be missed!

More Controversy:IADPSG Early Screening Paradigm Will Miss DM/GDM Cases


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Pros and Cons-You Decide

CC or NDDG criteria predict maternalDM risk, not pregnancy outcomes

Fasting not required for 50gm screen

Missed/delay in dx 2 step approach

Only used in U.S.

Clear criteria to screen early for GDM

Unclear diagnosis of overt DM butmost OBs use A1C of 6.5

Prevalence ~ 6-9% Some benefit supported by MFMU

data which used C/C

Inadequate resources to treat ifprevalence tripled; target obesity

Criteria based on HAPO fetaloutcomes; 1.75 OR risk arguable

Requires fasting; blood draws

No delay; precision of single value?

Global use of 75 gm OGTT

Early GDM missed with A1C, gluc

All/High Risk women receive A1C,FBG, or random glucose early

Prevalence ~18% Unclear benefit of treating IADPSG

criteria without large RCTs

Prediabetes 26% by NHANES; Whynot treat in pregnancy?

ACOG ADA


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Diabetes Care 2013;33(5):964

A COUNTRY DIVIDEDLack of consistent criteria forResearch Trials; Patient and Practitioner Confusion

ACOG

ADA, ES

Colorado Clinical Guidelines Collaborative 2007


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Colorado Clinical Guidelines Collaborative, 2007www.cdphe.state.co.us/

pp/womens/ges

tationaldiabetes

.html

Updated in2009

Dec l i ned

upda t i ng

in 2 013 .


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But Wait, ADA

Hedges.


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Final Thoughts

Lower maternal glycemia than previouslyrecognized contributes to infant adiposity, adverse outcomes

Obesity, GWG, diet, lipids, AAs, GFs, placental function,

oxidative stress, inflammation all contribute to LGA Whether adopting the IADPSG criteria without modifying above

will succeed in improving outcomes is unclear; Resources/cost?

As an Endocrinologist practicing in an OB setting, ACOG criteria

used; I would favor 75 mg OGTT with 2-fold OR cutoff Move to Canada OR

Intensify glucose targets if fetal AC is >90% on US (fetal based strategy)

Target Pre-Preg Wt Loss, Lower GWG than IOM Recs, Low Fat/Complex

Carb diet, TG lowering (diet, Omega-3) if high, Physical Activity (LGA)


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Genetics

Environment

Epigenetics

INSULIN RESISTANCE

Metabolic

Syndrome

Fetal Metabolic

Programming

TYPE 2

DIABETES

> 50%

e t s D iabes i t y : H a l t ing the Cy c l

Central Obesity

Hyperlipidemia

Glucose Intolerance

Inflammation/Ox Stress

High Fat Diet

2.4 barbour what guidelines to use in gestational diabetes

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