philippine cpg on diagnosis & screening for gestational diabetes

UNITE FOR DIABETES CPG

Screening and Diagnosis of Diabetes in

Pregnant Women

Iris Thiele Isip Tan MD, FPCP, FPSEMClinical Associate Professor

UP College of MedicineSection of Endocrinology, Diabetes & Metabolism

Department of Medicine, Philippine General Hospital

Should universal screening for diabetes be done among pregnant women?

Recommendation:

All pregnant women should be screened for gestational diabetes (Level 2, Grade B).

6.1

Should universal screening for diabetes be done among pregnant women?

6.1

ADAVery low risk* women need

not be screened

DIPSIUniversal screeninghigh GDM prevalence

in India

National GDM Technical Working

Party of N. Zealand Universal screening

NICEWomen with

any risk factor should be screened


Filipino women are at increased risk for diabetes in pregnancy.

ASGODIP Data n/N

Low risk 35/853

High risk 136/350

Overall171/1203

14.2%

Litonjua AD et al. AFES Study Group on Diabetes in Pregnancy: Preliminary Data on Prevalence. PJIM 1996:34:67-68.

6.1


RR for developing gestational diabetes by ethnicity (adjusted for age, BMI and parity; white as reference)

UK Data (1992) RR (95%CI)

Black 3.1 (1.8 to 5.5)

South East Asian 7.6 (4.1 to 14.1)

Indian 11.3 (6.8 to 18.8)

6.1

Dornhorst A, Paterson CM, Nicholls JSD, et al. High prevalence of gestational diabetes in women from ethnic minority groups. Diabetic Medicine 1992; 9:820–5.


6.1

http://www.flickr.com/photos/mikewade/3267336862/

Macrosomia

Birth injuries

http://www.flickr.com/photos/clairity/1385780317/

Shoulder Dystocia

Increased risk of

perinatal morbidity

http://www.flickr.com/photos/jessicafm/280232106/

Hypoglycemia

http://www.flickr.com/photos/tessawatson/379265818/










6.1

Treatment reduces perinatal morbidityACHOIS

Crowther et al. NEJM 2005; 352:2477-86.

Landon et al NEJM 2009; 361:1339-48.

ACHOISCrowther et al. NEJM 2005; 352:2477-86.

Crowther CA et al. Effect of Treatment of Gestational Diabetes Mellitus on Pregnancy Outcomes. NEJM 2005; 352:2477-86.

PI

MO

GDM24-28 wks AOG

Intervention (n=490)

diet CBG insulin vs

routine care (n=510)

Serious perinatal

complications

deathshoulder dystocia

bone fracturenerve palsy

Randomized controlled

trial

ACHOISCrowther et al. NEJM 2005; 352:2477-86.

Crowther CA et al. Effect of Treatment of Gestational Diabetes Mellitus on Pregnancy Outcomes. NEJM 2005; 352:2477-86.

PI

MO

GDM24-28 wks AOG


diet CBG insulin vs


Serious perinatal

complications

deathshoulder dystocia

bone fracturenerve palsy


trial

Any serious perinatal complication Adj RR 0.33 (95% CI 0.14-0.75), p=0.01

Landon et al NEJM 2009; 361:1339-48.

PI

MO


diet CBG insulin vs


Composite of stillbirth/perinatal

death and neonatal

complications


trial

“mild” GDM24-31 wks AOG

Landon MB et al. A multicenter, randomized trial of treatment for mild gestational diabetes. NEJM 2009; 361:1339-48.

hyperbilirubinemia hypoglycemia

hyperinsulinemia birth trauma

Landon et al NEJM 2009; 361:1339-48.

PI

MO


diet CBG insulin vs



death and neonatal

complications


trial





Composite endpoint RR 0.87 (95% CI 0.72-1.07), p=0.14

Landon et al NEJM 2009; 361:1339-48.

PI

MO


diet CBG insulin vs



trial




Landon et al NEJM 2009; 361:1339-48.

PI

MO


diet CBG insulin vs



trial




LGA infants RR 0.49

(95%CI 0.32-0.76) p<0.001

BW >4000 g RR 0.41

(95%CI 0.26-0.66) p<0.001


6.1

Cesearean Section

Pregnancy-induced hypertension

Preeclampsia

Increased risk of

maternal morbidity

Type 2 diabetes mellitushttp://www.flickr.com/photos/j2dread/4501366303/ http://www.flickr.com/photos/ulybug/512369383/

http://www.flickr.com/photos/78428166@N00/4921825364/

http://www.flickr.com/photos/j2dread/4501366303/

http://www.flickr.com/photos/j2dread/4501366303/

http://www.flickr.com/photos/ulybug/512369383/

http://www.flickr.com/photos/ulybug/512369383/




6.1

Treatment reduces maternal morbidity

Ratner et al JCEM 2008; 93:4774-9

Landon et al NEJM 2009; 361:1339-48

Landon et al NEJM 2009; 361:1339-48.

PI

MO


diet CBG insulin vs



death and neonatal

complications


trial





Landon et al NEJM 2009; 361:1339-48.

Cesarean delivery

RR 0.79 (0.64-0.99)

p=0.02


Preeclampsia

RR 0.46 (0.22-0.97)

p=0.02

Preeclampsia or gestational hypertension

RR 0.63 (0.42-0.96)

p=0.01

PI

MO

Women in DPP350 with previous GDM

1416 without

DPP arms placebo

metformin intensive lifestyle

Time to development of diabetes

semiannual FPG annual OGTT


trial

Ratner RE et al. Prevention of diabetes in women with a history of gestational diabetes: effects of metformin and lifestyle interventions. JCEM 2008;93: 4774-9

Ratner et al JCEM 2008; 93:4774-9

Ratner RE et al. Prevention of diabetes in women with a history of gestational diabetes: effects of metformin and lifestyle interventions. JCEM 2008;93: 4774-9We estimate that metformin therapy, on the other hand,

may be as much as 3 times more effective in reducing theincidence of diabetes in those with a history of GDM com-pared with those without. This may in part be explained by theyounger age (mean of 43 yr) of the GDM group becausewomen between 25 and 44 yr of age within DPP as a whole hada similar risk reduction with either metformin or ILS, butmetformin was no more effective than placebo in women overage 60 yr (5).

The Troglitazone in Prevention of Diabetes (TRIPOD)study data provide the closest comparison to the DPP results(15). TRIPOD enrolled an exclusively Latina population,

whereas DPP was ethnically mixed with 54% Caucasian. Inthe DPP, the GDM population was older (43 vs. 34 yr) andconsiderably more distant from their index pregnancies (12vs. ! 4 yr). As a result, we lost those individuals converting todiabetes in the early postpartum years before entering DPP.Nevertheless, parous female DPP participants, both with andwithout history of GDM, had a marked risk of progressing todiabetes (15.2 and 8.9 cases per 100 person-years, respec-tively) over the subsequent 3–5 yr. TRIPOD demonstrated a55% risk reduction with troglitazone treatment, comparablewith our observed reductions of 50.4% for metformin and53.4% for ILS among women with history of GDM.

0

5

10

15

20

25

30

35

40

45

0 0.5 1 1.5 2 2.5 3

Metformin (n=464)

Placebo (n=487)

ILS(n=465)

Cum

ulat

ive

inci

denc

e (%

)

Years from randomization

0

5

10

15

20

25

30

35

40

45

0 0.5 1 1.5 2 2.5 3Years from randomization

Cum

ulat

ive

inci

denc

e (%

)

Metformin (n=111)

Placebo (n=122)

ILS(n=117)

A

B

FIG. 4. Cumulative incidence of diabetes in DPP by randomized treatment group. Panel A, Women without a history of GDM; Panel B, women with a history of GDM.

4778 Ratner et al. Diabetes in Women with a History of GDM J Clin Endocrinol Metab, December 2008, 93(12):4774–4779

Cum

ulat

ive

inci

den

ce o

f dia

bet

es in

DP

P (%

)Without a history of GDM

With a history of GDM

Placebo

MetforminILS

Placebo

Metformin

ILS

} ~50% reduction

For pregnant women, when should screening be done?

Recommendations:

1. All pregnant women should be evaluated at the first prenatal visit for risk factors for diabetes (Level 4, Grade C).

6.2

6.2

USPSTFNo RCTs on screening before 24

weeks AOG

National GDM Technical Working

Party of N. Zealand Screen high risk

women at booking

NICEDetermine risk

factors for GDM at booking

appointment

http://www.flickr.com/photos/fdecomite/406635986/

ADAScreen high

risk women at first prenatal

visit

All pregnant women should be evaluated at the first prenatal visit for risk factors for diabetes (Level 4, Grade C).



Bartha et al. Am J Obstet

Gynecol 2000; 182:346-50.

Bartha JL et al. Gestational Diabetes Mellitus Diagnosed During Early Pregnancy. Am J Obstet Gynecol 2000; 182:346-50.

PI

MO

Pregnant at first prenatal visit

50-g GCT 1st visit then 24-28 weeks if initial result

normal (n=3986)

Early- (n=65) vs late-onset

(n=170) GDM

pregnancy complications, obstetric and

perinatal outcomes

Cross-sectional

comparative


Gynecol 2000; 182:346-50.


PI

MO



normal (n=3986)

Early- (n=65) vs late-onset

(n=170) GDM

pregnancy complications, obstetric and

perinatal outcomes

Cross-sectional

comparative

Women with an early diagnosis of GDM represent a high-risk subgroup


Gynecol 2000; 182:346-50.


PI

MO



normal (n=3986)

Early- vs late-onset GDM

Cross-sectional

comparative



Gynecol 2000; 182:346-50.


PI

MO



normal (n=3986)

Early- vs late-onset GDM

Cross-sectional

comparative


Likely hypertensive

(18.46% vs 5.88%,

p=0.006)

Higher need for insulin (33.85% vs

7.06%, p=0.0000)

Risk Factors for Gestational Diabetes

Prior history of GDM (OR 23.6 [95%CI 11.6, 48.0])3

Glucosuria (OR 9.04 [95%CI 2.6, 63.7]2; PPV 50% 4)

Family history of diabetes (OR 7.1 [95%CI 5.6, 8.9]1; OR 2.74 [95%CI 1.47, 5.11]3)

First-degree relative with type 2 diabetes (PPV 6.7%)4 First-degree relative with type 1 diabetes (PPV 15%)4Prior macrosomic baby (OR 5.59 [95%CI 2.68, 11.7])3

Age >25 years old (OR 1.9 [95%CI 1.3, 2.7]1; OR 3.37 [95%CI 1.45, 7.85]3)

1 Davey RX, Hamblin PS. Selective versus universal screening for gestational diabetes mellitus:

an evaluation of predictive risk factors. Medical Journal of Australia 2001;174(3):118–21.

2 Schytte T, Jorgensen LG, Brandslund I, et al. The clinical impact of screening for gestational diabetes. Clinical Chemistry and Laboratory Medicine 2004;42(9):1036–42.

3 Ostlund I, Hanson U. Occurrence of gestational diabetes mellitus and the value of different screening indicators for the oral glucose tolerance test. Acta Obstetricia et Gynecologica Scandinavica 2003;82(2):103–8.

4 Griffin ME, Coffey M, Johnson H, et al. Universal vs. risk factor-based screening for gestational diabetes mellitus: detection rates, gestation at diagnosis and outcome. Diabetic Medicine 2000;17(1):26–32.

Risk Factors for Gestational Diabetes

Diagnosis of polycystic ovary syndrome (OR 2.89 [95%CI 1.68, 4.98])5

Overweight or obese before pregnancy

(BMI >27 kg/m2 OR 2.3 [95%CI 1.6, 3.3]1; BMI>30 kg/m2 OR 2.65 [95%CI 1.36, 5.14]3

Macrosomia in current pregnancy (PPV 40% 4)Polyhydramnios in current pregancy (PPV 40% 4)Intake of drugs affecting carbohydrate metabolism

3 Ostlund I, Hanson U. Occurrence of gestational diabetes mellitus and the value of different screening indicators for the oral glucose tolerance test. Acta Obstetricia et Gynecologica Scandinavica 2003;82(2):103–8.

1 Davey RX, Hamblin PS. Selective versus universal screening for gestational diabetes mellitus: an evaluation of predictive risk factors. Medical Journal of Australia 2001;174(3):118–21.

4 Griffin ME, Coffey M, Johnson H, et al. Universal vs. risk factor-based screening for gestational diabetes mellitus: detection rates, gestation at diagnosis and outcome. Diabetic Medicine 2000;17(1):26–32.

5 Toulis KA, Goulis DG, Kolibiankis EM, Venetis CA, et al. Risk of gestational diabetes mellitus in women with polycystic ovary syndrome: a systematic review and a meta-analysis. Fertil Steril 2009;92(2):667–77.


Recommendations:

2. High-risk women should be tested at the soonest possible time (Level 3, Grade B).

6.2

6.2

DIPSIScreen early

“... fetal beta cell recognizes and

responds... as early as 16th week of

gestation.”

ADA Screen very

high risk women at first prenatal

visit

NICE Offer SMBG or OGTT at 16-18

wks AOG to women with

previous GDM

High-risk women should be tested at the soonest possible time (Level 3, Grade B).


Recommendations:

3. Routine testing for gestational diabetes is recommended at 24-28 weeks age of gestation for women with no risk factors (Level 3, Grade B).

6.2

6.2

USPSTFNo evidence

that screening after the 24th week

leads to reduction in morbidity &

mortality

ACHOISTreatment of

GDM after 24 wks AOG reduces complications

ADA Test “greater than low risk women” for GDM at 24-28

wks AOG

Routine testing for gestational diabetes is recommended at 24-28 weeks age of gestation (Level 3, Grade B).

NICE Offer OGTT at 24 to 28 wks AOG to women with other

risk factors


Recommendations:

4. Testing for gestational diabetes should still be carried out in women at risk, even beyond 24 to 28 weeks age of gestation (Level 3, Grade C).

6.2

Testing for gestational diabetes should still be carried out in women at risk, even beyond 24 to 28 weeks age of gestation (Level 3, Grade C).

6.2

Positive OGTT <26 weeks AOG >26 weeks AOG

Low risk15/2955.1%

20/5583.6%

High risk43/12035.8%

93/23040.4%

Litonjua AD et al. AFES Study Group on Diabetes in Pregnancy: Preliminary Data on Prevalence. PJIM 1996:34:67-68.


6.2

Sy RAG et al. Viewpoints on Gestational Diabetes: Report from ASGODIP Participating Hospital: Cardinal Santos Medical Center. PJIM 1996;34:45-48

>75% diagnosed GDM from 26 to 38 wks AOG

Higher morbidity rate (33%) in those

evaluated after 26th wk AOG

3 macrosomic babies

1 infant with multiple

congenital anomalies

and Down’s syndrome

ASGODIP Cardinal Santos Medical Center


6.2

Bihasa MTG et al. Screening for gestational diabetes: Report from ASGODIP participating hospital: Veterans Memorial Medical Center. PJIM 1996:34:57-61.

%AOG tested

<20 weeksn=19

21-30 weeksn = 74

31-40 weeksn = 60

Negative for GDM

95 92 85

Positive for GDM

5 8 15

ASGODIP (Veterans Memorial Medical Center)

Which tests should be used to screen pregnant women for gestational diabetes?

Recommendation:

An oral glucose tolerance test (OGTT), preferably the 75-g OGTT, should be used to screen for gestational diabetes (Level 3, Grade B).

6.3

6.3

IASDPGInitial visit

FPG, A1c or RPG 75-g OGTT at

24-28 wks ADA

One-step OGTT or two-step with GCT

ASGODIP 50-g GCT if low-risk

75-g OGTT if high-risk

An oral glucose tolerance test (OGTT), preferably the 75-g OGTT, should be used to screen for gestational diabetes (Level 3, Grade B).

DIPSI 75-g OGTT

NICE 75-g OGTT

Qualitative Strength

LR (+) LR (-)

Excellent 10 0.1

Very Good 6 0.2

Fair 2 0.5

Useless 1 1

Should we still do the 50-g glucose challenge test (GCT)?

NICE does not

recommend 50-g GCT

4 studies n=2437

LR(+) 4.34 95%CI(1.53,12.26)

LR(-) 0.42 95%CI(0.33,0.55)

Positive likelihood ratio: The increase in the odds of having the

disease after a positive test resultfair

National Institute for Health and Clinical Excellence. Diabetes in pregnancy: management of diabetes & its complications from pre-conception to the postnatal period. March 2008 (reissued July 2008)


Positive Predictive value The probability that a patient with a

positive test result will have the disease fair(+) OGTT (-) OGTT Total

(+) GCT 91 113 204

(-) GCT Not done 477

Total 681Positive

Predictive Value (PPV)

44.6%

Carlos-Raboca J et al. JAFES 2002;20:19-24


Only

moderately reproducible

More likely to be positive if conducted in the afternoon

Significantly affected by the time of the last

meal

http://www.flickr.com/photos/neeta_lind/3572379176/




10 to 23% of women fail to

return for OGTT after an initial

GCT

PGH (unpublished)

36% after (+) GCT

ASGODIPVeterans Memorial

17.8%1

FEU-NRMFH 48%2

after (+) GCT

http://www.flickr.com/photos/daquellamanera/4552683663/

1 De Asis TP et al. Incidence of gestational diabetes mellitus at Veterans Memorial Medical Center PJIM 1996; 34:63-66

2 Chua-Ho C et al. Screening for gestational diabetes mellitus: Report from ASGODIP Participating Hospital FEU-NRMFH PJIM 1996; 34:43-44



75-g or 100-g OGTT?

100-g more cumbersome;

4 blood samples

100-g OGTT duration 3 hours

100-g OGTT high glucose

load often unpalatable

75-g OGTT international standard in

non-pregnant

Head-to-head

studiesDeerochanawong

et al Diabetologia 1996;39:1070-3

Pettitt et al Diabetes Care 1994; 17(11):

1264-8

75-g or 100-g OGTT?

PI

MO

Pregnant Pima Indian women (n=127)

WHO 75-g OGTT

vs

NDDG 100-g OGTT

Macrosomia

Cesarean section

Cross-sectional

comparative

Pettitt DJ et al. Comparison of WHO and NDDG procedures to detect abnormalities of glucose tolerance during pregnancy. Diabetes Care 1994;17(11): 1264-8


1264-8

PI

MO


WHO 75-g OGTT

vs

NDDG 100-g OGTT

Cross-sectional

comparative



1264-8

PI

MO


WHO 75-g OGTT

vs

NDDG 100-g OGTT

Macrosomia

6/16 (38%) had (+) 75g

OGTT

1/16 (6%) had (+) 100 g

OGTT

Cross-sectional

comparative



1264-8

Cesarean section

4/7 (57%) had (+) 75g

OGTTNo one had (+)

100g OGTT

PI

MO

Pregnant 24-28 wks AOG (n=709)

WHO 75-g OGTT

vs

NDDG 100-g OGTT

Diagnosed GDM

Macrosomia

Cross-sectional

comparative

Deerochanawong et al. Comparison of NDDG and WHO criteria for detecting gestational diabetes. Diabetologia 1996;39: 1070-3

Deerochanawong et al Diabetologia 1996;39:1070-3

PI

MO


WHO 75-g OGTT

vs

NDDG 100-g OGTT

Diagnosed GDM

75-g OGTT 15.7%

(111/709)

100-g OGTT 1.4%

(10/709)

Cross-sectional

comparative



PI

MO


WHO 75-g OGTT

vs

NDDG 100-g OGTT

Diagnosed GDM

75-g OGTT 15.7%

(111/709)

100-g OGTT 1.4%

(10/709)

Cross-sectional

comparative



Macrosomia

6/14 (43%) (+)75g OGTT

3/14 (21%) (+)100 g OGTT

What criteria will be used to interpret the 75-g OGTT?

Recommendation:

The criteria put forth by the International Association of Diabetes & Pregnancy Study Groups (IADPSG) will be used to interpret the 75-g OGTT (Level 3, Grade B).

6.4

International Association of Diabetes and Pregnancy Study Groups Consensus Panel. IADPSG Recommendations on the Diagnosis and Classification of Hyperglycemia in Pregnancy. Diabetes Care 2010; 33(3):676-82.

Interpreting the 75-g OGTT

75-g OGTTThreshold(s) for diagnosing gestational

diabetes (mg/dL)

IADPSG* ADA**ASGODIP & DIPSI

FBS 92 95 -1-hour 180 180 -2-hour 153 155 140

*Any one value meeting threshold is considered gestational diabetes.** Two values must meet thresholds to be considered gestational diabetes

What other tests can be used to screen pregnant women for diabetes?

Recommendation:The following tests should not be used for the diagnosis of diabetes in pregnancy (Level 5, Grade D):

Capillary blood glucose FBS*

RBS* HbA1c

Fructosamine Urine glucose

Do an OGTT for those with glucosuria, elevated CBG or HbA1c.

6.5

* If available at consultation, use same diagnostic threshold for diabetes as in non-pregnant

6.5 CBG should not be used for the diagnosis of diabetes in pregnancy (Level 5,Grade D).

Different glucometers

used in studies

Validity of CBG vs OGTT

unproven

PostprandialCBG higher than venous

blood

Sensitivity 47-87%

Specificity 51-100%

6.5 FBS should not be used for the diagnosis of diabetes in pregnancy (Level 5,Grade D).

FBS varies with

advancing gestation

Paucity of data regarding reproducibility

Agardh C- D . Åberg A , Nordén N . Glucose levels and insulin secretion during a 75 g glucose challenge test in normal pregnancy. J Intern Med 1996 ; 240 : 303–9.

Lind T , Billewicz WZ , Brown G . A serial study of changes occurring in the oral glucose tolerance test in pregnancy J Obstet Gynaecol Br Com 1973 ; 80 : 1033–9 .

Kühl C . Glucose metabolism during and after pregnancy in normal and

gestational diabetic women . Acta Endocrinol 1975 ; 79 : 709–19.

Only 2 studies:

RBS vs OGTT

No optimal threshold for

RBS indicating an OGTT

RBS 6.5 mmol/L (117 mg/dL)

Sensitivity 75%Specificity 78%

6.5 RBS should not be used for the diagnosis of diabetes in pregnancy (Level 5,Grade D).

Jowett NI , Samanta AK , Burden AC . Screening for diabetes in pregnancy: Is a random blood glucose enough? Diabet Med 1987;4:160–3

Östlund I , Hanson U . Repeated random blood glucose measurements as universal screening test for gestational diabetes mellitus . Acta Obstet Gynecol Scand 2004;83:46–51

6.5 A1c should not be used for the diagnosis of diabetes in pregnancy (Level 5,Grade D).

HbA1c in normal women

varies with ethnicity and

gestation

HbA1c values did not differ

between normal women and those with

GDM

Loke DFM . Glycosylated haemoglobins in women with low risk for diabetes in pregnancy . Singapore Med J 1998;36:501–4

Agarwal M , Dhatt GS , Punnose J , Koster G . Gestational diabetes:a reappraisal of HBA1c as a screening test . Acta Obstet Gynecol Scand 2005;84:1159–63

6.5 Fructosamine should not be used for the diagnosis of diabetes in pregnancy (Level 5,Grade D).

Fructosamine varies with

ethnicity and albumin levels

Fructosamine did not differ

between normal women and those with

GDM

Bor MV , Bor P , Cevik C . Serum fructosamine and fructosamine - albumen ratio as screening tests for gestational diabetes mellitus . Gynecol Obstet 1999; 262:105–11

Huter O , Heinz D , Brezinka C , Soelder E , Koelle D , Patsch JR . Low sensitivity of serum fructosamine as a screening parameter for gestational diabetes mellitus . Gynecol Obstet Invest 1992;34:20–3

Cefalu WT , Prather KL , Chester DL , Wheeler CJ , Biswas M , Pernoll MI . Total serum glycated proteins in detection and monitoring of gestational diabetes . Diabetes Care 1990;13:872–5

Glucosuriatrace glucose

75 to >250 mg/dL

High ascorbic acid intake can

cause glucosuria

6.5 Urine glucose should not be used for the diagnosis of diabetes in pregnancy (Level 5,Grade D).

Sensitivity7-36%

Specificity83-98%

False-positive glucosuria

with high levels of urinary ketones

(starvation ketosis)

Comments/suggestions welcome

[email protected]

Thank Youhttp://www.endocrine-witch.info

mailto:[email protected]

mailto:[email protected]

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philippine cpg on diagnosis & screening for gestational diabetes

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