Journal of Adolescent Health 55 (2014) 79e84

www.jahonline.org

Original article

Diagnosing Dysglycemia in Adolescents With Polycystic

Ovary Syndrome
Holly Catherine Gooding, M.D. a, *, Carly Milliren, M.P.H. d, Michelle St. Paul a,
M. Joan Manseld, M.D. a, b, and Amy DiVasta, M.D. a, c
a
Division of Adolescent and Young Adult Medicine, Boston Childrens Hospital, Boston, Massachusetts
b
Division of Endocrinology, Boston Childrens Hospital, Boston, Massachusetts
c
Division of Gynecology, Boston Childrens Hospital, Boston, Massachusetts
d
Clinical Research Center, Boston Childrens Hospital, Boston, Massachusetts

Article history: Received July 12, 2013; Accepted December 18, 2013
Keywords: Adolescent; Polycystic ovarian syndrome; Screening; Diabetes

A B S T R A C T
IMPLICATIONS AND
CONTRIBUTION
Purpose: Screening for impaired glucose tolerance (IGT) is recommended for adolescents with
polycystic ovary syndrome (PCOS) with oral glucose tolerance test (OGTT). Whether glycated
Our study demonstrates
hemoglobin (HbA1c) can be used for screening in this patient population is unknown. We sought that both glycated hemo-
to determine the utility of HbA1c and 2-hour OGTT for diagnosing dysglycemia in adolescents globin (HbA1c) and oral
with PCOS. glucose tolerance test
Methods: This was a retrospective cohort study of 68 adolescents with PCOS seen in the Boston (OGTT) are useful for iden-
Childrens Hospital Division of Adolescent Medicine between 2008 and 2011 and not known to tifying adolescents with
have diabetes. Prevalence of dysglycemia (impaired fasting glucose, IGT, increased risk for diabetes, polycystic ovary syndrome
or diabetes mellitus as diagnosed by fasting plasma glucose, 2-hour OGTT, and/or HbA1c) and (PCOS) with dysglycemia
sensitivity and specicity of HbA1c for diagnosing dysglycemia compared with OGTT were and may identify different
assessed. populations of girls at risk for
Results: Twenty-four participants had abnormal glucose testing, including one participant (1.5%) long-term cardiometabolic
who met criteria for diabetes mellitus and 23 participants (34%) who met criteria for impaired consequences. Future stud-
fasting glucose/IGT/prediabetes. More patients were identied as having dysglycemia by HbA1c ies are necessary to deter-
than OGTT. Compared with OGTT, HbA1c had a sensitivity of 60% and a specicity of 69% for mine which test best predicts
diagnosing dysglycemia. future dysglycemia or pro-
Conclusions: In adolescents with PCOS, HbA1c had moderate sensitivity and specicity for gression to diabetes in lon-
detecting dysglycemia compared with OGTT. Clinicians should be aware that both tests have gitudinal follow-up.
benets and limitations, and the optimal test for follow-up requires further study.
2014 Society for Adolescent Health and Medicine. All rights reserved.

PCOS affects 5%e10% of reproductive-age women and often
presents during adolescence [1]. Many patients with PCOS are
insulin resistant even if they are not overweight or obese [2],
placing them at increased risk for developing impaired glucose
Conicts of Interest: The authors have no conicts of interest to disclose.
* Address correspondence to: Holly Catherine Gooding, M.D., Division of
Adolescent and Young Adult Medicine, Boston Childrens Hospital, 300 Long-
wood Avenue, Boston, MA 02115.
E-mail address: holly.gooding@childrens.harvard.edu (H.C. Gooding).
tolerance (IGT) and progression to diabetes mellitus (DM) [3e5].
Because IGT can present as early as adolescence in patients with
PCOS [6,7], health care providers are tasked with initiating the
evaluation for IGT and DM in these young women. The Androgen
Excess Society recommends IGT screening for adolescent and
adult women with PCOS who are obese, over 40 years of age, or
have a personal history of gestational diabetes or a family history
of type 2 diabetes [8] with a 2-hour OGTT, as fasting plasma
glucose (FPG) alone is less sensitive in this population [3]. The

1054-139X/$ e see front matter 2014 Society for Adolescent Health and Medicine. All rights reserved.
http://dx.doi.org/10.1016/j.jadohealth.2013.12.020
80 H.C. Gooding et al. / Journal of Adolescent Health 55 (2014) 79e84
American Diabetes Association (ADA) and American Academy of
Pediatrics recommend screening obese youth with two or more
risk factors for diabetes (one of which can be PCOS) with FPG [9].
Given that 70% of adolescents with PCOS are obese, the majority
will qualify for screening [10]. Despite these recommendations,
pediatric adolescent and gynecology providers report evalu-
ating only 25%e60% of adolescents diagnosed with PCOS for
IGT/DM [11].
In 2010, the ADA endorsed the use of HbA1c for the diagnosis
of diabetes in adults [12]. HbA1c is a reection of the average
blood glucose levels over the life of a red blood cell (approxi-
mately 90 days) and is closely associated with microvascular
disease in diabetes [13]. HbA1c is less subject to intraindividual
variation and does not require that the patient be fasting. This
latter advantage may be particularly relevant for adolescent
patients, for whom there may be barriers to access to care and
who may be less likely to return for follow-up [14]. However, the
Androgen Excess Society concluded in their 2010 position paper
that there were insufcient data on the use of HbA1c testing in
PCOS to recommend its use at that time [8].
Several recent studies have compared screening for dysglyce-
mia by HbA1c with either FPG or OGTT in adult [15e21] and
pediatric [22,23] groups, including adult women with PCOS
[24,25]. Most of these studies have found only fair agreement
among HbA1c, FPG, and OGTT. The role of HbA1c as a screening
tool in adolescents with PCOS has not been claried and may differ
from its use in adults due to the lower prevalence of dysglycemia
in adolescents. We thus sought to examine the prevalence of
dysglycemia as diagnosed by HbA1c and OGTT in adolescents with
PCOS to help clinicians identify strategies for clinical practice.
Methods
Participants
We used International Classication of Diseases (ICD-9) billing
codes to identify patients seen in our Adolescent and Young Adult
Medicine Clinic from 2008 to 2011 who were diagnosed with PCOS
by their treating clinician and underwent both a 2-hour OGTT and
HbA1c testing within 90 days (N 68, 45 of whom had both tests
on the same day), as well as N 125 individuals with PCOS who
did not have both OGTT and HbA1c testing for a comparison
sample. If multiple OGTT or HbA1c results were recorded within
the study period, those closest to the initial evaluation were used
for analysis. Data on demographic characteristics, social and family
history, physical examination ndings, laboratory studies, pelvic
ultrasound results, and treatment were collected through a stan-
dardized chart abstraction tool and entered into the RedCap
database [26]. All participants met 1990 National Institutes of
Health (NIH) Consensus Criteria for PCOS and thus had irregular
menses and either clinical or biochemical hyperandrogenism [27].
Participants were excluded if they had a prior diagnosis of type I or
type II diabetes or IGT or if they were taking medications known to
affect the results of an OGTT or HbA1c (such as metformin). This
study was approved by the Boston Childrens Hospital (BCH)
Committee on Clinical Investigations.
Demographic information
Age (in months/years) was dened by subtracting the date of
chart extraction from the participants date of birth. Race/
ethnicity was obtained from self-reported data from the
electronic patient registration system. Family history was
recorded by the treating clinician.
Measures
Body mass index (BMI) was calculated using the formula:
weight (kg)/height2 (m). Sexual maturity rating of pubertal
development for both breast and pubic hair was recorded by the
treating clinician. Blood pressure was obtained by GE Dinamap
DPC100X-US, measured in the right arm resting at heart level
with both feet on the ground per standard clinic policy.
Laboratory assays
An OGTT was performed in the morning on a random day of
the menstrual cycle in 68 fasting individuals who were instruc-
ted to consume a normal amount of carbohydrates for the 3 days
preceding the test in either the BCH clinical laboratory or another
certied laboratory (n 4). Blood glucose was measured at
baseline (FPG) and at 120 minutes (BG 120) after a 75 g oral
glucose load. ADA criteria [12] were used to classify participants
as having normal fasting glucose or glucose tolerance (FPG <
100 mg/dl or BG 120 < 140 mg/dl), impaired fasting glucose (IFG)
or IGT (FPG, 100e125 mg/dl or BG, 120 140e199 mg/dl), or dia-
betes (FPG  126 mg/dl or BG 120  200 mg/dl) based on their
OGTT results. For HbA1c results (turbidimetric inhibition
immunoassay, BCH clinical laboratory), we classied subjects as
normal if HbA1c < 5.7%, increased risk for diabetes if HbA1c
5.7%e6.4%, or diabetic if HbA1c  6.5% based on ADA criteria.
Additional laboratory values (total cholesterol, low density
lipoprotein cholesterol, high density lipoprotein cholesterol, tri-
glycerides, alanine aminotransferase, total and free testosterone
levels, dehydroepiandrosterone sulfate, and sex hormone bind-
ing globulin) were obtained using standard assays in either the
BCH clinical laboratory or another certied laboratory. Elevation
in testosterone levels was dened as values greater than the
normative range in that laboratory for a given patients sexual
maturity rating.
Statistical analysis
Descriptive statistics are presented as mean (SD) or frequency
(%). Median (interquartile range) are presented in lieu of mean
(SD) for continuous factors with non-normal distributions upon
visual inspection. Demographic and clinical factors at initial visit
were compared by HbA1c categories. All tests were performed at
an alpha level of .05 using SAS software, version 9.3 (SAS Institute
Inc., Cary, NC). Independent two-tailed t tests were used to assess
differences between participants classied as normal and
abnormal by HbA1c on continuous factors. Wilcoxon rank-sum
nonparametric test was used to assess differences between
HbA1c categories on continuous factors with a non-normal dis-
tribution where indicated in results and tables. Chi-square or
Fishers exact test (where appropriate) was used to assess dif-
ferences between the HbA1c categories on categorical factors.
Diagnostic characteristics of FPG and HbA1c were compared
using OGTT in terms of the predictive ability of these tests to
classify participants as having normal or abnormal glucose
ndings. Measures of the diagnostic ability calculated were
sensitivity, specicity, positive and negative likelihood ratios, and
the kappa statistic as a measure of overall agreement between the
test and the gold standard. Empirically derived cut points that
 H.C. Gooding et al. / Journal of Adolescent Health 55 (2014) 79e84 81

maximize sensitivity and specicity were also generated from the Table 1
data. Receiver operating characteristic (ROC) curves were con- Characteristics of study population at rst test by HbA1c categories (N 68)

structed using the binary OGTT result classication of normal Participant characteristic Normal Abnormal p Valueb
and abnormal as the gold standard to determine the predictive (<5.7%) (5.7%)
(n 44) (n 24)
ability of FPG and HbA1c at the range of all possible cut points
for these tests. To determine whether the test had good pre- n (%)a or n (%)a or
mean (SD) mean (SD)
dictive ability to discriminate glucose ndings, the areas under
the ROC curve (AUC) were compared with the null value of .5 Age (years) 16.6 (2.4) 17.1 (2.8) .43
(discrimination due to chance) using a ManneWhitney test to Race .03
White 30 (79%) 8 (21%)
construct 95% condence intervals (CIs) for the AUC. A test of the
Black or African-American 3 (38%) 5 (63%)
contrast between the ROC curves for HbA1c to FPG in reference Hispanic or Latino 3 (43%) 4 (57%)
to OGTT was also computed to discern whether the tests differed Other/Multiracial 2 (50%) 2 (50%)
from each other in terms of discriminatory ability. Family history of diabetes 13 (54%) 11 (46%) .18
Family history of PCOS 3 (75%) 1 (25%) .99
BMI z-score 1.8 (1.1) 1.9 (.7) .84
Results BMI categoryc .99
Normal 5 (71%) 2 (29%)
Demographic and clinical characteristics of the 68 patients Overweight 3 (60%) 2 (40%)
who completed both OGTT and HbA1c testing within 90 days, Obese 30 (63%) 18 (38%)
Systolic BP (mm Hg) 116.8 (14.8) 116.0 (14.4) .83
stratied by HbA1c category, are listed in Table 1. The median Diastolic BP (mm Hg) 65.8 (10.5) 66.6 (10.5) .79
time between OGTT and HbA1c testing was 0 days (interquartile Total cholesterol (mg/dl) 150.5 (24.8) 166.6 (23.0) .10
range 23.5). Findings did not differ when analysis was restricted LDL cholesterol (mg/dl) 79.4 (25.9) 104.8 (24.9) .04
to the 45 individuals who had OGTT and HbA1c testing on the HDL cholesterol (mg/dl)* 44.1 (18.3) 41.55 (13.05) .75
Triglycerides (mg/dl)* 93.5 (90) 105 (64.5) .75
same day. Compared with 125 patients with PCOS seen during
ALT (IU/L)* 21 (14) 19 (8.5) .34
the same period who did not have both OGTT and HbA1c testing, Total testosterone (ng/dl) 49.7 (22.4) 44.8 (21.9) .43
patients who had both tests performed had higher BMI Z-scores Free testosterone (pg/dl)* 7.85 (6.7) 7.05 (6.55) .70
(1.83 vs. 1.27, p < .01). However, patients with both tests per- DHEAS (mg/dl)* 204.1 (141.5) 222.3 (340.8) .38
formed were no more likely to have a family history of DM and SHBG (nmol/L)* 16.0 (21.0) 18.0 (10.0) .78
PCOS diagnosisd
did not differ from other PCOS patients with respect to race/ Clinical hyperandrogenism 39 (64%) 22 (36%) .99
ethnicity, age, or free testosterone (pg/dl). (n 61)
Subjects with an HbA1c  5.7% were more likely to be black Biochemical 37 (67%) 18 (33%) .19
(p .03) and to have higher low-density lipoprotein cholesterol hyperandrogenism (n 55)
(p .04) compared with individuals with a normal HbA1c. There Median (IQR) reported for continuous factors noted above by * due to non-
were no statistically signicant differences by HbA1c category in normal distribution.
other cardiometabolic risk factors, including blood pressure and ALT alanine aminotransferase; BMI body mass index; BP blood pressure;
DHEAS dehydroepiandrosterone sulfate; HbA1c hemoglobin A1c; HDL
BMI, nor in androgen levels or criteria met for PCOS diagnosis.
high density lipoprotein; IQR interquartile range; LDL low density lipopro-
Subjects with an HbA1c  5.7% had higher mean FPG levels and tein; PCOS polycystic ovarian syndrome; SD standard deviation; SHBG sex
were more likely to have an abnormal 2-hour glucose (Table 2). hormone binding globulin.
a
There were no statistically signicant differences by OGTT category Percentages are of those with complete data on a given variable. Totals for
in demographic variables, androgen concentrations, homeostasis each characteristic do not necessarily equal 68 due to missing data.
b
Independent two-tailed t tests were used to assess differences between
model assessment of insulin resistance, or cardiometabolic risk participants classied as normal and abnormal by HbA1c on continuous
factors (data not shown). factors. Wilcoxon rank-sum test was used to assess differences between the
One subject was classied as having diabetes; this subject met HbA1c categories on continuous factors with non-normal distribution (indicated
criteria for diabetes by both HbA1c and OGTT. Three patients were by *). Chi-square or Fishers exact test (where appropriate) was used to assess
differences between the HbA1c categories on categorical factors.
classied as having IFG on the basis of an abnormal FPG, while nine c
BMI categories were determined by pediatric percentiles for subjects under
subjects were classied as having IGT based upon BG 120. Twenty- 18 years of age and by adult cutoffs for subjects 18 years of age or older.
three patients were classied at increased risk for diabetes by d
All subjects met 1990 NIH criteria for PCOS and thus had oligomenorrhea and
HbA1c. Due to the low number of patients with DM in our sample, either clinical or biochemical hyperandrogenism. Forty-nine (75%) of subjects
DM and IFG/IGT/increased risk for diabetes were considered had both clinical and biochemical hyperandrogenism.

together as dysglycemia for all remaining analyses. The majority of

patients (N 22, 84%) with abnormal glucose testing of any type
diagnosis of dysglycemia than FPG in this cohort when compared
were obese; HbA1c was no more or less likely than OGTT to
with OGTT. The AUC for continuous HbA1c was .68 (95% CI
identify normal or overweight individuals as having dysglycemia.
.49e.87), and the AUC for continuous FPG was .67 (95% CI
Figure 1 shows the number of patients diagnosed as having
.48e.86). After adjusting for race/ethnicity and family history of
dysglycemia by each of the three tests. HbA1c failed to classify four
diabetes, the AUC for HbA1c improved to .80 and the AUC
individuals identied as abnormal by BG 120 and one individual
improved to .85 for FPG.
identied as abnormal by FPG, but identied 17 individuals as
abnormal who were not identied by either component of the
OGTT. Only one individual was identied as abnormal by all three Discussion
tests. Compared with OGTT, HbA1c had a sensitivity of 60.0% and a
specicity of 69.0% for diagnosing dysglycemia (Table 3); these In this study of 68 adolescents with PCOS presenting for
values did not differ for the empirically derived cut point of 5.6%. clinical care and completing both OGTT and HbA1c testing, 43%
HbA1c was more sensitive but less specic for making the had an abnormal value on at least one screening test for
82 H.C. Gooding et al. / Journal of Adolescent Health 55 (2014) 79e84

Table 2
OGTT and FPG results by HbA1c categories (N 68)

Participant characteristic Normal (<5.7%; n 44) Abnormal (5.7%; n 24) p Valuea

n (%) or mean (SD) Range n (%) or mean (SD) Range

FPG (mg/dl) 83.9 (9.6) 67.0e125.0 88.3 (9.0) 68.0e111.0 .07

FPG category .28
Normal (<100 mg/dl) 43 (66%) 22 (34%)
Impaired (100e125 mg/dl) 1 (33%) 2 (67%)
Diabetes (>125 mg/dl) 0 (0%) 0 (0%)
2-Hour glucose (mg/dl) 108.2 (24.8) 56.0e177.0 118.9 (36.2) 71.0e219.0 .15
2-Hour glucose category .13
Normal (<140 mg/dl) 40 (69%) 18 (31%)
Impaired (140e199 mg/dl) 4 (44%) 5 (56%)
Diabetes (>199 mg/dl) 0 (0%) 1 (100%)

FPG fasting plasma glucose; HbA1c hemoglobin A1c; OGTT oral glucose tolerance testing; SD standard deviation.
a
Independent two-tailed t tests were used to assess differences between participants classied as normal and abnormal by HbA1c on continuous factors. Chi-
square or Fishers exact test (where appropriate) was used to assess differences between the HbA1c categories on categorical factors.

dysglycemia. The majority were identied as at risk for dia-
betes by an abnormal HbA1c, but four individuals with dysgly-
cemia were identied only by 2-hour glucose levels and one was
identied with FPG only. Compared with OGTT, HbA1c had a
sensitivity of 60.0% and a specicity of 69.0% for diagnosing
dysglycemia.
Similar to our study, two recent studies have looked at HbA1c
as a screening tool for diabetes in adult women with PCOS [24,25]
and found only fair agreement between HbA1c and OGTT results,
reporting a kappa statistic of .29 [24], a sensitivity of 35%, and a
specicity of 99% for the diagnosis of diabetes [25]. Interestingly,
Magnussen et al. found HbA1c had a stronger correlation with
other important cardiovascular risk factors (such as BMI and lipid
proles) than the OGTT [25]. We did not nd signicant differ-
ences in cardiometabolic risk factors by HbA1c or OGTT category
in our adolescent sample, which may reect the relatively normal
cardiometabolic parameters in this younger age group. Impor-
tantly, neither test was more likely to identify dysglycemia in the
small number of nonobese adolescents with PCOS in our sample.
A recent editorial cautioned against the premature adoption of
HbA1c as a screening strategy in youth, noting that a criteria of
6.5% for diagnosis of diabetes may be too high in children and
adolescents [28]. Others have noted that at thresholds of 5.7% and
6.5%, HbA1c testing may not be as cost effective as OGTT as a
screening test for dysglycemia [29]. However, it is important to
recognize that the reproducibility of the OGTT in overweight
children is itself poor, with only 30% of youth having concordant
Figure 1. Diagnosis of dysglycemia by FPG, 2-hour OGTT, or HbA1c in 29 of 68
patients with PCOS.
results on OGTTs performed on two separate days [30]. Thus while
the sensitivity and specicity of HbA1c for diagnosing IGT and DM
are indeed suboptimal in our study and other studies of adoles-
cents compared with OGTT, HbA1c testing may actually identify
some individuals not identied on the OGTT or FPG due to the
intraperson variability of day-to-day glucose processing [31]. This
may be particularly true for adolescents who often consume high
glucose loads from sugar-sweetened beverages and other foods
high in carbohydrate content [32]. Alternatively, elevated HbA1c
results may represent false-positive results. Long-term follow-up
studies examining whether HbA1c or OGTT measured in adoles-
cence best predicts the development of microvascular and mac-
rovascular complications of diabetes in adulthood are needed to
resolve this distinction.
Study limitations should be acknowledged. Our study was
based upon a retrospective design and included patients with
PCOS evaluated at one academic medical center, and thus results
may not be generalizable to other adolescent populations. Test
ordering and completion were at the discretion of the provider
and patient, and not surprisingly, both tests were obtained more
often in adolescents who were obese, consistent with screening
guidelines. We report results based on one test date and as
intraindividual variation with glucose testing occurs, the ADA
recommends two tests to conrm a diagnosis of diabetes [12].
Although OGTT and HbA1c testing were done on the same day in
only 66% of cases, the two tests are often done at different times
in actual clinical practice, and our results did not change when
we restricted to the individuals who had both tests on the same
day. Although data are not available regarding the timing of
testing within the menstrual cycle, the majority of patients with
PCOS are anovulatory and thus expected to be in the follicular
phase. Finally, some participants may have already engaged in
lifestyle modications at the instruction of their treating clini-
cian before testing. Despite these limitations, this study provides
important data on both the high prevalence of abnormal glucose
testing in a population of predominantly overweight and obese
adolescents with PCOS and on the utility of HbA1c compared
with OGTT for diagnosing early problems with glucose homeo-
stasis in these young women.
Given the high prevalence of dysglycemia and the lack of a
single measure identied in our study and other studies [24,25],
a clear recommendation for a screening strategy in adolescent
women with PCOS cannot be made. We propose two possible
strategies, both of which require additional study. The rst,
 H.C. Gooding et al. / Journal of Adolescent Health 55 (2014) 79e84
Table 3
Sensitivity and specicity of HbA1c and FPG for diagnosing dysglycemia in adolescents with PCOS compared with 2 hour OGTT (N 68)
Sensitivity (%)
HbA1c
Consensus cut point (5.7%) 60.0
Empirically determined cut point (>5.6%) 60.0
Fasting glucose
Consensus cut point (>99 mg/dl) 10.0
Empirically determined cut point (>87 mg/dl) 80.0
FPG fasting plasma glucose; HbA1c hemoglobin A1c; LR positive likelihood ratio; LR negative likelihood ratio; OGTT oral glucose tolerance test; PCOS
polycystic ovary syndrome.
advocated by several experts, is the rule-in, rule-out approach,
where a FPG or OGTT is used to follow-up intermediate values of
HbA1c between 5.5% and 7.0% [33]. Given that adolescents may
be particularly reluctant to return for fasting laboratory tests, this
strategy would be simplest for most clinicians to implement
and is likely preferred by those in primary care practice [34].
An alternative approach involves measurement of both HbA1c
and OGTT at the initial evaluation with repeated measurement of
the more abnormal test on a separate day. If IGT or increased risk
for diabetes is conrmed on either test, this test could be followed
at regular intervals to measure change with lifestyle modication
or medication therapy. Either of these strategies has the potential
to increase both nancial [29] and psychological costs due to false-
positive results. A prospective study comparing these strategies
over time would allow assessment of outcomes and cost.
Adolescent girls with PCOS are at high risk for dysglycemia.
Based on our results, it appears that both HbA1c and OGTT are
useful for identifying adolescents with PCOS with dysglycemia
and may actually identify different populations of girls at risk for
long-term cardiometabolic consequences. Future studies are
necessary to determine whether OGTT or HbA1c results best
predict future dysglycemia or progression to diabetes in longi-
tudinal follow-up. In the meantime, clinicians need to be aware
of the characteristics and limitations of each of the glucose
screening tests available and continue to counsel all adolescents
with PCOS on the benets of lifestyle modication for the pre-
vention of diabetes. It is our opinion that the best screening
strategy is the one most likely to be completed by clinicians and
their patients in order to identify, counsel, and treat those
patients at highest risk for diabetes.
Acknowledgments
The authors thank our patients, their families, and our clinical
providers as well as Dr. S. Jean Emans and Dr. Henry Feldman for
thoughtful comments on study design and analysis. Dr. Gooding
drafted the manuscript; none of the authors were paid an hon-
orarium for this work.
Funding Sources
Personnel support for data collection was funded in part by
the Leadership Education in Adolescent Health Training Program
MCH/HSRA T71MC00009 and Dr. DiVasta is supported by NICHD
K23HD060066; neither funder directly sponsored the study nor
inuenced data collection or interpretation.
83
Specicity (%) LR LR Kappa c Statistic
69.0 1.93 .58 .18 .645
69.0 1.93 .58 .18 .645
97.0 3.33 .93 .09 .533
62.0 2.11 .32 .23 .710
References
[1] Orsino A, Van Eyk N, Hamilton J. Clinical features, investigations and
management of adolescents with polycystic ovary syndrome. Paediatr
Child Health 2005 Dec;10:602e8.
[2] Dunaif A, Segal KR, Futterweit W, et al. Profound peripheral insulin resis-
tance, independent of obesity, in polycystic ovary syndrome. Diabetes 1989
Sep;38:1165e74.
[3] Legro RS, Kunselman AR, Dodson WC, et al. Prevalence and predictors of risk
for type 2 diabetes mellitus and impaired glucose tolerance in polycystic
ovary syndrome: A prospective, controlled study in 254 affected women.
J Clin Endocrinol Metab 1999 Jan;84:165e9.
[4] Ehrmann DA, Barnes RB, Roseneld RL, et al. Prevalence of impaired
glucose tolerance and diabetes in women with polycystic ovary syndrome.
Diabetes Care 1999 Jan;22:141e6.
[5] Legro RS, Gnatuk CL, Kunselman AR, et al. Changes in glucose tolerance
over time in women with polycystic ovary syndrome: A controlled study.
J Clin Endocrinol Metab 2005 Jun;90:3236e42.
[6] Palmert MR, Gordon CM, Kartashov AI, et al. Screening for abnormal
glucose tolerance in adolescents with polycystic ovary syndrome. J Clin
Endocrinol Metab 2002 Mar;87:1017e23.
[7] Nur MM, Newman IM, Siqueira LM. Glucose metabolism in overweight
Hispanic adolescents with and without polycystic ovary syndrome. Pedi-
atrics 2009 Sep;124:e496e502.
[8] Wild RA, Carmina E, Diamanti-Kandarakis E, et al. Assessment of cardio-
vascular risk and prevention of cardiovascular disease in women with the
polycystic ovary syndrome: A consensus statement by the Androgen
Excess and Polycystic Ovary Syndrome (AE-PCOS) Society. J Clin Endocrinol
Metab 2010 May;95:2038e49.
[9] Type 2 diabetes in children and adolescents. American Diabetes Associa-
tion. Pediatrics 2000 Mar;105(3 Pt 1):671e80.
[10] Bekx MT, Connor EC, Allen DB. Characteristics of adolescents presenting to
a multidisciplinary clinic for polycystic ovarian syndrome. J Pediatr Adolesc
Gynecol 2010 Feb;23:7e10.
[11] Bonny AE, Appelbaum H, Connor EL, et al. Clinical variability in approaches
to polycystic ovary syndrome. J Pediatr Adolesc Gynecol 2012 Aug;25:
259e61.
[12] American Diabetes Association. Diagnosis and classication of diabetes
mellitus. Diabetes Care 2010 Jan;33(Suppl 1):S62e9.
[13] Sacks DB. A1C versus glucose testing: A comparison. Diabetes Care 2011
Feb;34:518e23.
[14] Peters A, Laffel L. Diabetes care for emerging adults: Recommendations for
transition from pediatric to adult diabetes care systems: A position state-
ment of the American diabetes Association, with representation by the
American College of Osteopathic Family Physicians, the American Academy
of Pediatrics, the American Association of Clinical Endocrinologists, the
American Osteopathic Association, the Centers for Disease Control and
Prevention, Children with Diabetes, The Endocrine Society, the Interna-
tional Society for Pediatric and Adolescent Diabetes, Juvenile Diabetes
Research Foundation International, the National Diabetes Education Pro-
gram, and the Pediatric Endocrine Society (formerly Lawson Wilkins
Pediatric Endocrine Society). Diabetes Care 2011 Nov;34:2477e85.
[15] Heianza Y, Hara S, Arase Y, et al. HbA1c 5.7-6.4% and impaired fasting
plasma glucose for diagnosis of prediabetes and risk of progression to
diabetes in Japan (TOPICS 3): A longitudinal cohort study. Lancet 2011 Jul
9;378:147e55.
[16] Jorgensen ME, Bjerregaard P, Borch-Johnsen K, et al. New diagnostic
criteria for diabetes: Is the change from glucose to HbA1c possible in all
populations? J Clin Endocrinol Metab 2010 Nov;95:E333e6.
[17] Carson AP, Reynolds K, Fonseca VA, et al. Comparison of A1C and fasting
glucose criteria to diagnose diabetes among U.S. adults. Diabetes Care 2010
Jan;33:95e7.
84 H.C. Gooding et al. / Journal of Adolescent Health 55 (2014) 79e84
[18] Lipska KJ, De Rekeneire N, Van Ness PH, et al. Identifying dysglycemic
states in older adults: Implications of the emerging use of hemoglobin A1c.
J Clin Endocrinol Metab 2010 Dec;95:5289e95.
[19] Olson DE, Rhee MK, Herrick K, et al. Screening for diabetes and pre-
diabetes with proposed A1C-based diagnostic criteria. Diabetes Care
2010 Oct;33:2184e9.
[20] James C, Bullard KM, Rolka DB, et al. Implications of alternative denitions of
prediabetes for prevalence in U.S. adults. Diabetes Care 2011 Feb;34:387e91.
[21] Mann DM, Carson AP, Shimbo D, et al. Impact of A1C screening criterion on
the diagnosis of pre-diabetes among U.S. adults. Diabetes Care 2011 Oct;
33:2190e5.
[22] Nowicka P, Santoro N, Liu H, et al. Utility of hemoglobin A(1c) for diagnosing
prediabetes and diabetes in obese children and adolescents. Diabetes Care
2011 Jun;34:1306e11.
[23] Lee JM, Wu EL, Tarini B, et al. Diagnosis of diabetes using hemoglobin A1c:
Should recommendations in adults be extrapolated to adolescents?
J Pediatr 2011 Jun;158:947e52. e941-943.
[24] Hurd WW, Abdel-Rahman MY, Ismail SA, et al. Comparison of diabetes
mellitus and insulin resistance screening methods for women with poly-
cystic ovary syndrome. Fertil Steril 2011 Oct;96:1043e7.
[25] Velling Magnussen L, Mumm H, Andersen M, et al. Hemoglobin A1c as a
tool for the diagnosis of type 2 diabetes in 208 premenopausal women
with polycystic ovary syndrome. Fertil Steril 2011 Nov;96:1275e80.
[26] Harris PA, Taylor R, Thielke R, et al. Research electronic data capture
(REDCap)ea metadata-driven methodology and workow process for
providing translational research informatics support. J Biomed Inform 2009
Apr;42:377e81.
[27] Zawadski J, Dunaif A. Diagnostic criteria for polycystic ovary syndrome:
Towards a rational approach. In: Dunaif A, Givens JR, Haseltine FP, et al., eds.
Polycystic Ovary Syndrome. Boston, MA: Blackwell Scientic Publications;
1992:377e84.
[28] Kester LM, Hey H, Hannon TS. Using hemoglobin A1c for prediabetes and
diabetes diagnosis in adolescents: Can adult recommendations be upheld
for pediatric use? J Adolesc Health 2012 Apr;50:321e3.
[29] Wu EL, Kazzi NG, Lee JM. Cost-effectiveness of screening strategies for
identifying pediatric diabetes mellitus and dysglycemia. JAMA Pediatr
2013;167:32e9.
[30] Libman IM, Barinas-Mitchell E, Bartucci A, et al. Reproducibility of the oral
glucose tolerance test in overweight children. J Clin Endocrinol Metab 2008
Nov;93:4231e7.
[31] Inzucchi SE. Clinical practice. Diagnosis of diabetes. N Engl J Med 2012 Aug
9;367:542e50.
[32] Forbes LE, Storey KE, Fraser SN, et al. Dietary patterns associated with
glycemic index and glycemic load among Alberta adolescents. Appl Physiol
Nutr Metab 2009 Aug;34:648e58.
[33] Herman WH, Cohen RM. Racial and ethnic differences in the relationship
between HbA1c and blood glucose: Implications for the diagnosis of dia-
betes. J Clin Endocrinol Metab 2012 Apr;97:1067e72.
[34] Lee JM, Eason A, Nelson C, et al. Screening practices for identifying type 2
diabetes in adolescents. J Adolesc Health 2013 Aug 19.