Original Article

Obstetric Medicine
6(3) 125–128
! The Author(s) 2013
Diagnostic effectiveness of 75 g oral glucose Reprints and permissions:
sagepub.co.uk/journalsPermissions.nav
tolerance test for gestational diabetes DOI: 10.1177/1753495X13482895
obm.sagepub.com
in India based on the International
Association of the Diabetes and Pregnancy
Study Groups guidelines
Tarakeswari Surapaneni1, Irfana Nikhat2 and
Praveen K Nirmalan3

Abstract
Background: To determine the diagnostic effectiveness of the fasting and one-hour plasma glucose levels for gestational diabetes (GDM) based on
International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria.
Methods: A Cross-sectional study that included 2348 pregnant women booked for antenatal care in 2011 at a tertiary care perinatal institute. Pregnant
women underwent a 75 g oral glucose tolerance test (OGTT) between 24 and 28 weeks of gestation. Outcome measures include the incidence of GDM
based on the IADPSG criteria and the diagnostic effectiveness of the recommended fasting and one-hour plasma glucose cut-off if used in isolation.
Results: The incidence of GDM was 21.81% (n ¼ 520, 95% CI: 20.15, 23.57) with the IADPSG criteria. A fasting plasma glucose cut-off 92 mg/dL, in
isolation, correctly classified 87.16% of GDM, with a specificity of 96.08%, clinically significant positive likelihood ratio (14.08) and a post-test probability of
79.71%. The one-hour 75 g test, in isolation, correctly classified 85.74% of GDM, had specificity of 99.68% and clinically significant positive likelihood ratio
(111.12) and post-test probability of 96.87%. The application of the World Health Organization criteria would misclassify 11.91% (95% CI: 10.66, 13.26) of
GDM as normal.
Conclusions: Additional testing of plasma glucose levels can be avoided for 18.25% (n ¼ 435, 95% CI: 16.73, 19.84) if the IADPSG diagnostic criteria
for GDM are applied with exit on a positive fasting or one-hour test result.

Keywords
gestational diabetes mellitus, IADPSG criteria, oral glucose tolerance test

Introduction determine the diagnostic effectiveness if we use only one of the fasting
and one-hour test values (sequential testing) for the diagnosis of GDM.
Approximately 79 million people are expected to have diabetes mellitus
in India by the year 2030.1 Gestational diabetes (GDM), a metabolic
complication of pregnancy, has a reported prevalence that varies from Methods
9.9% to 17.8% in India.2 Hyperglycaemia in pregnancy has short- and
long-term maternal and neonatal consequences although interventions Pregnant women booked for care at the study institute have a stan-
for GDM can reduce adverse outcomes.3–9 Accurate detection of dardized antenatal care examination that includes details of medical,
GDM through a standardized test is essential to initiate interventions surgical and obstetric history, personal risk behaviours, clinical exams
and to understand the wide variations in reported prevalence of GDM. and investigations including trimester specific ultrasound exams and
Several methods have been used to diagnose GDM a 75 g oral glucose laboratory investigations. These details are entered into a medical
tolerance test (OGTT) at two-hours (World Health Organization record and transcribed into an electronic database. We used a retro-
[WHO] recommendation) and a three-hour 100 g OGTT based on spective design to retrieve information on pregnant women booked for
the American Diabetic Association (ADA) guidelines.10–12 Recently, antenatal care based on a study protocol that adhered to the tenets of
a consensus guideline, the International Association of the Diabetes the Declaration at Helsinki and protected patient privacy. Written
and Pregnancy Study Groups (IADPSG) recommendations, has been informed consent from pregnant women is sought and documented
adopted to standardize the determination of GDM globally.13 The after counselling at registration to use their medical records for
IADPSG recommendations have two major changes compared with research and education with complete protection of their privacy.
the WHO or ADA protocol. One, the IADPSG recommends a 75 g Each woman re-assured that their clinical care will not be compro-
three test approach – a fasting plasma glucose determination and mised or affected in any manner if they do not provide consent to
repeat plasma glucose determination at one- and two-hours after
oral ingestion of 75 g glucose. Two, a pregnant woman is considered
1
to have GDM if any of the three test values are higher than the rec- High Risk Pregnancy & Obstetric Medicine, Fernandez Hospital,
ommended thresholds. Conversely, GDM is considered absent in a Hyderabad, India
2
pregnant woman if all three test values are normal. The IADPSG Michael Diagnostics, Fernandez Hospital, Hyderabad, India
3
guidelines were adopted for the detection of GDM at the Fernandez Clinical Research Unit, Fernandez Hospital, Hyderabad, India
Hospital, an advanced tertiary care perinatal institute at Hyderabad,
India, in 2011. The current study was designed to determine the impact Corresponding author:
of adopting the IADPSG guidelines at this institute focused specifically Tarakeswari Surapaneni, Fernandez Hospital, Hyderabad, India.
on (a) the changed incidence of gestational diabetes and (b) to Email: tarakeswari@gmail.com

Downloaded from obm.sagepub.com at UQ Library on July 14, 2015

use their medical records for educational or research purposes. The Table 1 Characteristics of the 2384 women who participated in
study protocol was approved by the institutional review board. the study.
Pregnant women undergo a 75 g OGTT test between 24 and 28
weeks of gestation as part of a universal screening protocol. The Characteristic N (%)
OGTT test involves measurement of plasma glucose levels after an
overnight fast (8 hours), followed by oral consumption of 75 g glucose, Maternal age 35 years 105 (4.40%)
and plasma glucose measurement at one and two hours. A plasma Primigravid 1073 (45.01%)
fasting blood glucose 4126 mg/dL in a pregnant woman is considered Body mass index 430 428 (17.95%)
as overt diabetes (after confirmation) even if there is no prior history of Body mass index 25–30 512 (21.48%)
diabetes. Gestational diabetes is defined as a fasting plasma glucose
Normal body mass index 1205 (50.53%)
value 492 mg/dL or a one-hour plasma glucose value 4180 mg/dL or a
two-hour plasma glucose value 4153 mg/dL. Gestational diabetes is Body mass index 518.5 239 (10.03%)
considered absent if a pregnant woman has normal values at Gestational hypertension 73 (3.67%)
all three test intervals. We excluded pregnant women with overt dia- Pre-eclampsia 57 (2.39%)
betes mellitus (prior history and/or a fasting plasma glucose level Chronic hypertension 36 (1.51%)
4126 mg/dL) and women who did not complete the OGTT test from
Screen positive hypothyroid 84 (3.52%)
the study. We defined hypertensive disorders in pregnancy based on the
working group recommendations of high blood pressure in preg- Mean (SD) gestational age at delivery (weeks) 37.71 (2.95)
nancy.14 We defined a preterm delivery as 537 weeks of gestation Preterm 537 weeks gestation 279 (11.70%)
and macrosomia as a birth weight 44 kg. A trained neonatologist
determined the postdelivery fetal growth using Lubchenco charts and SD ¼ standard deviation.
categorized babies as small for gestational age, average for gestational
age and large for gestational age.
We analysed the data using the statistical software STATA version
9.0 (College station, TX, USA). We determined the prevalence and Table 2 Incidence of gestational diabetes using the different
95% confidence intervals (CI) of GDM based on the IADPSG and IADPSG criteria.
the WHO recommendations. The determination of GDM based on the
IADPSG criteria involves any one of three positive values and requires Criteria Incidence, % (95% CI)
three blood draws and test that may not be feasible in resource poor
settings with busy obstetric practices. We explored to check if the Fasting plasma glucose 492 mg/dL 15.10 (13.71, 16.58)
testing can be limited using a sequential approach in such situations, 1-hour plasma glucose 4180 mg/dL 8.05 (7.01, 9.20)
thus, limiting further testing if the fasting plasma glucose value was 2-hour plasma glucose 4153 mg/dL 9.19 (8.08, 10.40)
492 mg/dL or one-hour plasma glucose value was 4180 mg/dL. We Fasting and 1-hour plasma glucose positive 4.91 (4.09, 5.83)
tested this using tests of diagnostic effectiveness sensitivity, specificity
Fasting or 1-hour plasma glucose positive 18.25 (16.73,19.84)
and likelihood ratios, and area under receiver operator characteristic
curve (AUROC) of the different cut-off values of fasting and one-hour Fasting and 1-hour and 2-hour plasma 0.38 (0.18, 0.69)
OGTT test, using the values in isolation and in comparison with GDM glucose positive
diagnosed based on the WHO criteria. We looked at the likelihood Any one of Fasting, 1-hour or 2-hour plasma 21.8 (20.15, 23.57)
ratios as they are more useful than predictive values to apply in clinical glucose positive (IADPSG criteria)
practice. A positive likelihood ratio 410 is considered clinically
significant. IADPSG ¼ International Association of the Diabetes and Pregnancy Study
Groups.

Results
needing two-hour 75 g OGTT could be reduced by an additional
The study included 2384 pregnant women booked for antenatal care 3.71% (n ¼ 75, 95% CI: 2.89, 4.53) if we exclude pregnant women
with a mean age (SD) of 27.18 (3.95) years (range 18–45 years). The with one-hour 75 g OGTT plasma glucose levels 4180 mg/dL from
characteristics of these 2384 women are presented in Table 1. The further testing. Overall, additional testing of plasma glucose levels
prevalence of GDM was 17.20% (n ¼ 410, 95% CI: 15.68, 18.71) can be avoided for 18.25% (n ¼ 435, 95% CI: 16.73, 19.84) if the
based on the WHO criteria and increased to 21.81% (n ¼ 520, 95% IADPSG diagnostic criteria for GDM are applied with exit on a posi-
CI: 20.15, 23.57) with the IADPSG criteria. One hundred and seventy- tive fasting or one-hour test result.
four (7.30%, 95% CI: 6.31, 8.40) pregnant women are false-positives We did not find significant associations with outcomes of preg-
and 284 (11.91%, 95% CI: 10.66, 13.26) are false-negatives if we use nancy; however, these data are not discussed as the study did not
the WHO criteria for the diagnosis of GDM with the IADPSG criteria have enough power to explore for associations of GDM with outcomes
considered as the gold standard. Table 2 presents the different identi- of pregnancy.
fication rates if we use the IADPSG cut-off values in isolation or as
several combinations.
The diagnostic effectiveness of different fasting plasma glucose Discussion
levels and the one-hour 75 g OGTT, if used in isolation was explored
in comparison with the WHO criteria as the gold standard. The diag- Gestational diabetes is an emerging problem among pregnant women
nostic effectiveness of fasting plasma glucose 492 mg/dL (AUROC in India.15 The wide variation in reported incidence of GDM in India
0.81, 95% CI: 0.78, 0.83) was better but did not differ significantly indicates the need for a reliable, standardized and replicable diagnostic
from the one-hour 75 g OGTT value (AUROC 0.76, 95% CI: 0.73, or screening test.2 More than one in five pregnant women in this study
0.78) to discriminate between pregnant women with and without was determined to have GDM based on the IADPSG criteria. We
GDM. The number of pregnant women needing one-hour 75 g found that fasting and one-hour 75 g OGTT using the IADPSG cut-
OGTT could be reduced by 15.10% (n ¼ 360, 95% CI: 13.67, 16.54) offs has good diagnostic properties in this population and that add-
if we exclude pregnant women with fasting plasma glucose levels itional testing can be reduced for nearly one in five pregnant women if
492 mg/dL from further testing. The number of pregnant women test results are applied with exit on a positive test result at fasting or

Downloaded from obm.sagepub.com at UQ Library on July 14, 2015

one hour. These results may suggest that exit based on a fasting or one- waiting time and convenience including blood draws for pregnant
hour OGTT can result in a substantial saving in terms of tests done as women. However, this relative advantage has to be balanced against
well as waiting period for pregnant women. However, further studies clinical outcomes of pregnancy and potential associations of the three
are necessary on associations of GDM with clinical outcomes of preg- values (in isolation and combination) with such outcomes. A previous
nancy in this population, prior to any recommendations to exit the study has reported the differential risk for adverse outcomes of preg-
OGTT on a positive fasting or one-hour result. nancy associated with different combinations of abnormal glucose
The application of the test and the consequences of a false-positive values.16 Pregnant women with elevated postglucose load levels and
or a false-negative result determine the choice of a diagnostic or screen- normal fasting glucose levels were more likely to have preterm
ing test. The preferred cut-off values that determine the accuracy of a deliveries, hypertensive disorders in pregnancy or a neonate with
test depend on a relative benefit-harm ratio if we misclassify pregnant hyperbilirubinemia.16 Pregnant women with elevated fasting glucose
women as false-positives or false-negatives. If we consider maternal levels but normal postglucose load levels were more likely to have a
and neonatal adverse events associated with GDM, the misclassifica- large for gestational age baby.16 We did not have sufficient power to
tion of a normal pregnant woman as having GDM, although not ideal, explore for and comment on such associations. Additionally, non-
is relatively less serious than the consequences of missing a pregnant pharmacological and pharmacological interventions are provided
woman with GDM. to women with GDM and the potential beneficial effects of these inter-
The two-hour cut-off with the IADPSG criteria is much higher than ventions on associations with outcomes have to be considered.
the two-hour cut-off with the WHO criteria. However, the inclusion of In summary, the IADPSG criteria have good specificity, positive
a fasting or a one-hour cut-off for the diagnosis of GDM with the likelihood ratio and post-test probabilities for GDM in this popula-
IADPSG criteria leads to a higher incidence of GDM as a proportion tion. The consistent use of IADPSG criteria may help standardize the
of previously normal pregnant women are now categorized as GDM. determination of GDM in India and provide comparable estimates
We found that the application of the WHO criteria would have led us within India and across the world. However, the cost-effectiveness of
to misclassify 11.91% (95% CI: 10.66, 13.26) of pregnant women with the test has to be ascertained prior to widespread use.
GDM as normal. Evaluating the effectiveness of using only the fasting
and one-hour 75 g OGTT values assume great significance in resource
poor settings.
Acknowledgments
We found that the use of only a fasting plasma glucose cut–off None
492 mg/dL could correctly classify 87.16% of pregnant women with
GDM (using the WHO criteria as the gold standard). This cut-off has a Declaration of Conflicting Interests
very high specificity (96.08%) and a clinically significant positive like-
lihood ratio (14.08). Both the specificity and the positive likelihood None.
ratio indicate that the fasting plasma glucose cut–off 492 mg/dL is a
clinically useful cut-off. The high specificity of the test can also be used Funding
to rule in the disease of interest, in this instance, GDM. The disease or
The study was supported by the Fernandez Hospital Educational and
condition can be ruled in if a test with a high specificity gives a positive
Research Foundation, Hyderabad.
test result. The positive likelihood ratio of 14.08 tells us that a positive
test result is 14 times more likely to come from a pregnant woman with
GDM compared with a pregnant woman without GDM. The one-hour Ethical approval
75 g test, used in isolation, correctly classified 85.74% of pregnant
The study was approved by the Institutional Review Board of
women with GDM (using the WHO criteria as the gold standard),
Fernandez Hospital Pvt Ltd, Hyderabad, India 500001
but had a higher specificity (99.68%) and clinically very significant
positive likelihood ratio (111.12). A positive test result with the one-
hour 75 g OGTT (4180 mg/dL) thus rules in GDM and indicates that Guarantor
the pregnant woman is 111 times more likely to have GDM compared Dr Tarakeswari Surapaneni
with a pregnant woman without GDM.
Diagnostic test parameters can be translated into clinical practice to
optimally utilize the test results for clinical management. A positive test Contributorship
result should increase the post-test probability of the disease to lead to IN was involved with the design of the study, data collection, inter-
a diagnosis. We can determine the post-test probability based on the pretation of results and writing of the manuscript, TS was involved
prevalence of the disease and the positive likelihood ratio of the test with the design, interpretation and writing of the manuscript. PKN
criteria. We found that a positive fasting plasma glucose 492 mg/dL was involved with the design, data analysis and interpretation of results
increased the probability of disease from 21.81% (95% CI: 20.15, and writing of the manuscript.
23.57) to 79.71% (95% CI: 78.04, 81.28). A positive one-hour 75 g
plasma glucose value 4180 mg/dL increased the probability of disease
even further from 21.81% (95% CI: 20.15, 23.57) to 96.87% (95% CI: References
96.56, 97.16). These results indicate that the use of fasting plasma 1. Wild S, Roglic G, Green A, Sicree R and King H. Global preva-
glucose 492 mg/dL or a one-hour 75 g plasma glucose value lence of diabetes. Diabetes Care 2004; 27: 1047–1053.
4180 mg/dL, in isolation, is also useful to discriminate pregnant 2. Seshiah V, Balaji V, Balaji SM, Sanjeevi CB and Green A.
women with and without GDM. Gestational diabetes mellitus in India. J Assoc Physicians India
Intuitively, these results indicate that we can limit the two-hour test 2004; 52: 707–711.
to pregnant women considered normal with the fasting and the one- 3. Metzger BE, Lowe LP, Dyer AR, et al. HAPO Study Cooperative
hour 75 g OGTT. We could also consider limiting the complete OGTT Research Group. Hyperglycaemia and adverse pregnancy out-
to persons with a fasting plasma value 485 mg/dL to 92 mg/dL or a comes. N Engl J Med 2008; 358: 1991–2002.
one-hour plasma glucose value 4160 mg/dL to 80 mg/dL using the 4. Kim C, Newton KM and Knopp RH. Gestational diabetes and the
sensitivity to rule out a disease and the likelihood ratios. The post-test incidence of type 2 diabetes: a systematic review. Diabetes Care
probabilities for GDM are 36.04% with a fasting plasma glucose value 2002; 25: 1862–1868.
of 485 mg/dL and 53.95% with a one-hour plasma glucose value 5. Plagemann AJ. A matter of insulin: developmental programming of
4160 mg/dL. Limiting the complete OGTT to these subgroups pro- body weight regulation. Matern Fetal Neonatal Med 2008; 21:
vides a major advantage in terms of resources and logistics, and 143–148.

Downloaded from obm.sagepub.com at UQ Library on July 14, 2015

6. Tam WH, Ma RC, Yang X, et al. Glucose intolerance and cardi- 11. American Diabetes Association. Gestational diabetes mellitus.
ometabolic risk in adolescents exposed to maternal gestational Diabetes Care 2007; 30(Suppl. 1): S7.
diabetes: a 15-year follow-up study. Diabetes Care 2010; 33: 12. American College of Obstetricians and Gynecologists. Diabetes
1382–1384. and pregnancy. Technical Bulletin No. 200; 1994.
7. Crowther CA, Hiller JE, Moss JR, McPhee AJ, Jeffries WS and 13. International Association of Diabetes and Pregnancy Study
Robinson JS Australian Carbohydrate Intolerance Study in Groups. International Association of Diabetes and Pregnancy
Pregnant Women (ACHOIS) Trial Group. Effect of treatment of Study Groups recommendations on the diagnosis and classifica-
gestational diabetes mellitus on pregnancy outcomes. N Engl J tion of hyperglycemia in pregnancy. Diabetes Care 2010; 33:
Med 2005; 352: 2477–2486. 676–682.
8. Langer O, Yogev Y, Most O and Xenakis EM. Gestational dia- 14. Report of the National High Blood Pressure Education Program
betes: the consequences of not treating. Am J Obstet Gynecol 2005; Working Group on High Blood Pressure in Pregnancy. Am J
192: 989–997. Obstet Gynecol 2000;183:S1–S22.
9. Landon MB, Spong CY, Thom E, et al. Eunice Kennedy Shriver 15. Surapaneni T and Fernandez E. Obesity in gestational diabetes:
National Institute of child health and human development mater- emerging twin challenge for perinatal care in India. Int J Infertil
nal-fetal medicine units network. A multicenter, randomized trial Fetal Med 2010; 1: 35–39.
of treatment for mild gestational diabetes. N Engl J Med 2009; 361: 16. Black MH, Sacks DA, Xiang AH and Lawrence JM. Clinical out-
1339–1348. comes of pregnancies complicated by mild gestational diabetes
10. Alberti KG and Zimmet PZ. Definition, diagnosis and classifica- mellitus differ by combinations of abnormal oral glucose tolerance
tion of diabetes mellitus and its complications. Part 1: diagnosis test values. Diabetes Care 2010; 33: 2524–2530.
and classification of diabetes mellitus provisional report of a WHO
consultation. Diabet Med 1998; 15: 539–553.

Downloaded from obm.sagepub.com at UQ Library on July 14, 2015