Diagnosis of Diabetes using Hemoglobin A1c: Should Recommendationsin Adults Be Extrapolated to Adolescents?

Joyce M. Lee, MD, MPH, En-Ling Wu, BA, Beth Tarini, MD, MS, William H. Herman, MD, MPH, and Esther Yoon, MD, MPH

Objective To compare test performance of hemoglobin A1c (HbA1c) for detecting diabetes mellitus/pre-diabetesfor adolescents versus adults in the United States.

g plasma glucose [FPG]$126mg/dL; 2-126 mg/dL; 140# 2-hr PG

substantially more adolescents with pre-diabetes (on the basisof either FPG or 2-hr PG measures) than with undiagnosed

THE JOURNAL OF PEDIATRICS www.jpeds.com Vol. 158, No. 6study of the US civilian non-institutionalized population.NHANES has a stratified multi-stage probability samplingdesign,7 which over-samples adolescents, non-Hispanicblack, and Mexican-American individuals to provide reliablestatistical estimates.We focused on individuals who had both FPG and HbA1c

measures, and for a subanalysis of individuals with a 2-hr PGand HbA1c. Both FPG and the 2-hr PG have limitations foridentifying diabetes mellitus because of poor concordance8

and lack of reproducibility.9,10 However, because FPG or 2-hr PG were the recommended tests for diagnosis of diabetesmellitus, we used them as the best method to compare withHbA1c. Procedures on the assessment of fasting status, bloodcollection, sample processing, and analysis of FPG and 2-hrPG in NHANES have been described in earlier publica-tions.11,12 HbA1c was measured with two high-performanceliquid chromatography systems (PrimusCorporation, KansasCity,Missouri, and TosohMedics, San Francisco, California),which were standardized to the reference method used for theDiabetes Control and Complications Trial.13

Of the 21 056 and 6873 subjects aged 12 to 79 years fromNHANES 1999 to 2004 and NHANES 2005 to 2006, respec-tively, we examined individuals with both HbA1c and FPGmeasures during the morning examination after fasting fora minimum of 8 hours. We excluded subjects who were preg-nant at the time of the exam (n = 1350) or who reported anearlier diagnosis of diabetes mellitus (n = 1824). We analyzeddata on 1156 overweight and obese adolescents aged 12 to 18years, because the ADA recommends that only overweightand obese adolescents be screened,14 and compared themwith data from 6751 adults aged 19 to 79 years.4 Our adultpopulation included normal weight and overweight/obeseindividuals because adults can be targeted for screening re-gardless of weight.4 Furthermore, we also conducted ouranalyses on a subpopulation of adults aged 45 to 79 years be-cause of the recommendation to screen adults$45 years old.Because these findings were similar to those for our entireadult population, the results are not shown. In addition, weanalyzed data from a subsample of 267 adolescents and1476 adults who had 2-hr PG measures from an oral glucosetolerance test (OGTT) during NHANES 2005 to 2006.Our outcomes of interest were diabetes mellitus and pre-

diabetes, on the basis of definitions using both FPG, whichwas available for all study years, and 2-hr PG, which wasavailable for NHANES 2005 to 2006. Individuals were classi-fied as having diabetes mellitus when they had an FPG$126mg/dL or pre-diabetes when they had an FPG $100 mg/dLand

year

1999-2004 2005-2006

e saren.

June 2011 ORIGINAL ARTICLESof FPG, an HbA1c cutoff point of 5.7% resulted in slightly

Survey (n = 874) (n = 282)

SexMale 467 (56.1) 129 (48.1)Female 407 (43.9) 153 (51.9)

RaceWhite 185 (58.0) 56 (58.1)Black 288 (17.5) 93 (17.3)Mexican-American 338 (13.3) 114 (16.4)Other 63 (11.2) 19 (8.2)

Age (years)19-29 30-39 40-49 50-59 60-69 70-79

Weight status

Normal weight Overweight 422 (48.8) 131 (49.6)Obese 452 (51.2) 151 (50.4)

Glucose tolerance statusNormal 756 (86.5) 215 (71.8)Impaired fasting glucose/

glucose tolerance (prediabetes)115 (12.9) 66 (28.1)

Undiagnosed diabetes 3 (0.6) 1 (0.1)

n (weighted %).*Describes demographic characteristics for only children who were overweight and obese in thProportions are calculated on the basis only of children who were overweight and obese childTable I. Characteristics of the study population

Adolescents (12-18

FPGhigher estimates of sensitivity, slightly lower estimates ofspecificity, and a slightly higher positive predictive value.HbA1c under-diagnosed pre-diabetes even more severelyon the basis of 2-hr PG results compared with FPG results.

Figure 1 shows the ROC curves for predicting diabetesmellitus (FPG $126 mg/dl) in adolescents and adults atvarious thresholds of HbA1c. HbA1c was not as gooda predictor of diabetes mellitus for adolescents (AUC, 0.88;95% CI, 0.66 to 1.00) compared with adults (AUC, 0.93;95% CI, 0.91 to 0.95), although the difference was notstatistically significant (P = .68).

Figure 2 shows the ROC curves for predicting pre-diabeteswith either FPG or 2-hr PG in adolescents and adults atvarious thresholds of HbA1c. HbA1c was a poor predictorof pre-diabetes for adolescents compared with adults witheither FPG (AUC, 0.61; 95% CI, 0.56 to 0.65 [adolescents]versus AUC, 0.74; 95% CI, 0.72 to 0.75 [adults], P < .01)or 2-hr PG (AUC, 0.53; 95% CI, 0.39 to 0.67 [adolescents]versus AUC, 0.73; 95% CI, 0.70 to 0.76 [adults], P < .01).The summary of test performance characteristics predict-

ing diabetes mellitus and pre-diabetes across HbA1c thresh-olds are shown in Table III (available at www.jpeds.com).

Discussion

When the International Expert Committee recommended us-ing HbA1c to diagnose diabetes mellitus in the pediatric pop-

Diagnosis of Diabetes using Hemoglobin A1c: Should RecommeExtrapolated to Adolescents?ulation as in adults, it did so without considering the test

s)* Adults (19-79 years)

2-hr PG FPG 2-hr PG

2005-2006(n = 267)

1999-2004(n = 5139)

2005-2006(n = 1612)

2005-2006(n = 1476)

123 (47.8) 2610 (49.7) 860 (51.8) 794 (48.9)144 (52.2) 2529 (50.3) 752 (48.2) 682 (51.1)

52 (58.1) 2501 (72.8) 772 (72.3) 715 (72.1)87 (17.9) 1008 (10.0) 377 (10.8) 329 (10.7)

110 (15.1) 1229 (7.4) 332 (7.8) 316 (8.1)18 (8.9) 401 (9.8) 131 (9.1) 116 (9.1)

1206 (20.6) 417 (20.8) 358 (21.0) 900 (21.4) 287 (19.8) 268 (21.6) 958 (23.0) 315 (23.6) 295 (22.2) 704 (17.1) 219 (17.8) 210 (17.5) 811 (10.8) 216 (10.8) 200 (10.8) 560 (7.1) 158 (7.2) 145 (6.9)

1749 (36.4) 531 (34.4) 484 (34.5)121 (47.2) 1780 (34.8) 520 (32.1) 479 (31.3)146 (52.8) 1535 (28.8) 545 (33.5) 505 (34.2)

247 (92.3) 3452 (69.5) 959 (61.8) 1158 (80.5)20 (7.7) 1506 (27.7) 594 (35.1) 227 (14.3)

0 (0.0) 181 (2.8) 59 (3.1) 91 (5.2)

mple.performance of HbA1c in adolescents. We found that at therecommended HbA1c threshold of 6.5% for the diagnosisof diabetes mellitus according to FPG in adolescents, the sen-sitivity estimate (75%) was highly unstable, with wide confi-dence intervals (95% CI, 30.1 to 95.4). This instability iscaused, in large part, by the low prevalence of diabetes melli-tus in the pediatric population. Moreover, our ROC curvesfor predicting diabetes mellitus demonstrate that HbA1cdoes not appear to have the same level of discrimination foradolescents compared with adults. Together, these findingshighlight that extrapolation of adult HbA1c testing recom-mendations to the pediatric population is likely premature.Alternative HbA1c thresholds to those used in adults may

be useful for the pediatric population. The ROC curve for pre-dicting diabetesmellitus in adolescents was based on a limitednumber of individuals; therefore, additional analyses withsufficient numbers of adolescents with diabetes mellitus arenecessary before any firm recommendation can be made asto what constitutes an appropriate HbA1c level for diagnosisof diabetes mellitus in this age group. However, we speculatethat a lower HbA1c threshold should be explored for adoles-cents, because studies have shown that HbA1c increases withage in the population.18 The committees choice of an HbA1cthreshold of 6.5% for adults was in part based on anHbA1c of6.5% representing just 3 SDs higher than the mean for adultsin the United States and the high specificity rate (99.6%) andreasonable sensitivity rate (43% to 44%) at this threshold onthe basis of NHANES III and NHANES 1999 to 2004 data.3

ndations in Adults Be 949

Table II. Test performance characteristics of a hemoglobin Aaccording to fasting plasma glucose or 2-hour plasma glucosedetecting pre-diabetes according to fasting plasma glucose or

Criterion Age group Total n Cases n S

Diabetes mellitus (HbA1c 6.5%)FPG Adolescents 1156 4

Adults 6751 240

2-hr PG Adolescents 267 0Adults 1476 91

Pre-diabetes (HbA1c 6.0%)FPG Adolescents 1156 181

Adults 6751 2100

2-hr PG Adolescents 267 20

Adults 1476 227

Pre-diabetes (HbA1c 5.7%)FPG Adolescents 1156 181

Adults 6751 2100

2-hr PG Adolescents 267 20

THE JOURNAL OF PEDIATRICS www.jpeds.com Vol. 158, No. 6Adults 1476 227

PPV, positive predictive value; NPV, negative predictive value.The notion of a lower threshold for adolescents is sup-ported by the findings of one recent study based on theBogalusa Heart Study, although it is based on FPG criteria.Nguyen et al found that children with an FPG of 86 to 99

Figure 1. Receiver operator characteristic curves of variousthresholds of HbA1c for predicting diabetes mellitus (definedwith FPG $126 mg/dL) in adolescents (AUC, 0.88; 95% CI,0.66 to 1.00) and adults (AUC, 0.93; 95% CI, 0.91 to 0.95).

9501c threshold of 6.5% for detecting diabetes mellitusand hemoglobin A1c thresholds of 6.0% and 5.7% for2-hour plasma glucose in adolescents and adults

ensitivity (95% CI)Specificity(95% CI) PPV NPV

75.0%(30.1-95.4)

99.9%(99.5-100.0)

75.0% 99.9%

53.8%(47.4-60.0)

99.5%(99.3-99.6)

79.1% 98.3%

30.8%

(22.2-40.9)99.6%

(99.2-99.9)84.8% 95.6%

1.1%(0.3-3.9)

99.4%(98.7-99.7)

25.0% 84.4%

11.4%(10.1-12.9)

94.7%(94.0-95.3)

49.3% 70.3%

0.0%(0.0-16.1)

99.6%(97.7-99.9)

0.0% 92.5%

13.2%(9.4-18.2)

93.0%(91.4-94.3)

25.4% 85.5%

5.0%(2.6-9.2)

98.3%(97.2-98.9)

34.6% 84.8%

23.1%(21.3-25.0)

91.1%(90.3-91.9)

54.0% 72.4%

0.0%(0.0-16.1)

97.6%(94.8-98.9)

0.0% 92.3%

26.9%(21.5-33.0)

87.2%(85.2-88.9)

27.6% 86.8%mg/dL had a >2-fold risk of the development of adult pre-diabetes and type 2 diabetes mellitus compared with childrenwith an FPG

resL (AU

June 2011 ORIGINAL ARTICLESrecommendations of phasing out glucose measurements fordetecting pre-diabetes and using HbA1c in its place, most ad-olescents with pre-diabetes would be missed.We acknowledge the practical appeal of using HbA1c

rather than plasma glucose levels for detecting diabetes mel-litus, especially in the pediatric population. Compared withHbA1c levels, plasma glucose levels are not perfectly stableand are subject to diurnal21 and laboratory variation.22 Incontrast, the HbA1c test can be obtained non-fasting, is stable

Figure 2. Receiver operator characteristic curves of various thadults. Pre-diabetes was defined either by A, FPG $100 mg/d0.74; 95%CI, 0.72 to 0.75 in adults) orB, 2-hr PG$140mg/dL (95% CI, 0.70 to 0.76 in adults).at room temperature, and has less day-to-day and within-person variability. Furthermore, there has been standardiza-tion of HbA1c assays across laboratories,3 and a variety ofepidemiologic studies have demonstrated a link betweenHbA1c levels$6.5% and increased rates of diabetic retinop-athy in adult populations.23,24 We also note that because ofthe high negative predictive values of HbA1c for predictingdiabetes mellitus and pre-diabetes, HbA1c may be a clinicallyuseful test to exclude a diagnosis of pre-diabetes or diabetesmellitus for at-risk adolescents.However, there are disadvantages for the use of HbA1c,

such as racial/ethnic variation in HbA1c levels (ie, higherlevels of HbA1c by 0.4% to 0.7% for African-American pa-tients compared with Caucasian patients)25,26 and medicalconditions that can affect HbA1c levels independent of glu-cose levels. For example, hemolytic anemia and active bleed-ing can lead to decreases in erythrocyte age, which lowersHbA1c; this glucose-independent lowering of HbA1c couldpossibly lead to a missed diagnosis of diabetes mellitus. Incontrast, iron-deficiency anemia, splenectomy, or aplasticanemia can lead to higher HbA1c levels; this glucose-independent increase in HbA1c could possibly lead to anerroneous diagnosis of diabetes mellitus.3 Although thecommittee recommends that providers perform glucose tests

Diagnosis of Diabetes using Hemoglobin A1c: Should RecommeExtrapolated to Adolescents?(FPG or 2-hr PG) rather than HbA1c for patients with theseconditions, most pediatric providers in the primary care set-ting are not familiar with these limitations of HbA1c, poten-tially leading to diagnostic errors.Our findings contrast with a recent study suggesting that

HbA1c could be a useful marker for identifying adolescentswith pre-diabetes and diabetes mellitus.26 They found thatoptimal sensitivity and specificity to detect type 2 diabetesmellitus were 99% and 96%, respectively, at an HbA1c

holds of HbA1c for predicting pre-diabetes in adolescents andAUC, 0.61; 95% CI, 0.56 to 0.65 in adolescents versus AUC,C, 0.53; 95%CI, 0.39 to 0.67 in adolescents versus AUC, 0.73;threshold $6.0%. Their reported levels of sensitivity andspecificity were notably higher than our estimates. However,their population of adolescents who were obese and a sub-group of adolescents who were obese and insulin-resistantwere referred to an obesity clinic and may have had symp-toms of diabetes mellitus. Therefore these results are notgeneralizable to an population-based sample of adolescentswithout symptoms in the pediatric primary care setting. Fur-thermore, their estimates were based on a total of 3 cases oftype 2 diabetes mellitus from a cohort of 193 children.They do not report confidence intervals for their estimatesof sensitivity and specificity, but based on the low numberof cases, it is likely that the confidence intervals, similar toour study, were quite high.We do acknowledge limitations to our study. Our find-

ings relate to HbA1c testing of overweight and obese chil-dren without symptoms, rather than with symptoms.Earlier studies have used NHANES data to evaluate the per-formance of HbA1c for predicting diabetes mellitus inadults,5,6 but we are unaware of studies that have systemat-ically compared its performance for adults compared withchildren. Despite FPG being measured in the morning,which maximizes the prevalence of diabetes detected,21

the number of individuals with diabetes mellitus in the

ndations in Adults Be 951

mellitus prevalencewithNHANEShave used similarmethodsfor identifying undiagnosed diabetes mellitus and pre-diabe-

9. Libman IM, Barinas-Mitchell E, Bartucci A, Robertson R, Arslanian S.

THE JOURNAL OF PEDIATRICS www.jpeds.com Vol. 158, No. 6tes.30 Furthermore, studies in both adolescents9 and adults10

suggest that FPG has better reproducibility compared witha 2-hr PG. We do recognize, however, that one abnormalmeasurement of HbA1c is not sufficient for diagnosis of dia-betesmellitus, because additional testing in the clinical settingwould likely be needed to confirm the clinical diagnosis. Inconclusion, use of HbA1c as a tool for diagnosing diabetesamong adolescents likely requires further consideration andstudy. n

Submitted for publication Mar 25, 2010; last revision received Sep 14, 2010;

accepted Nov 8, 2010.

Reprint requests: Joyce Lee, MD, MPH, Assistant Professor, Pediatric

Endocrinology and Health Services Research, Child Health Evaluation and

Research Unit, University of Michigan, 300 NIB, Room 6E18, Campus Box

5456, Ann Arbor, MI 48109-5456. E-mail: joyclee@umich.edu

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Table III. Test performance characteristics of specific hemoglobin A1c thresholds for detecting diabetes mellitusaccording to fasting plasma glucose and pre-diabetes according to fasting plasma glucose or 2-hour plasma glucose inadolescents and adults

HbA1c threshold

Diabetes (FPG), adolescents Diabetes (FPG), adults

Sensitivity(true-positive

rate)

Specificity(true-negative

rate)

Positivelikelihood

ratio PPV NPV

Sensitivity(true-positive

rate)

Specificity(true-negative

rate)

Positivelikelihood

ratio PPV NPV

3.6 - - - - - 1.00 0.00 1.00 0.043.8 - - - - - 1.00 0.00 1.00 0.04 1.004.0 1.00 0.00 1.00 0.00 1.00 0.00 1.00 0.04 1.004.1 1.00 0.00 1.00 0.00 1.00 1.00 0.00 1.00 0.04 1.004.2 - - - - - 1.00 0.00 1.00 0.04 1.004.3 1.00 0.00 1.00 0.00 1.00 1.00 0.00 1.00 0.04 1.004.4 1.00 0.01 1.01 0.00 1.00 1.00 0.01 1.01 0.04 1.004.5 1.00 0.01 1.01 0.00 1.00 1.00 0.01 1.01 0.04 0.984.6 1.00 0.02 1.02 0.00 1.00 0.99 0.02 1.01 0.04 0.984.7 1.00 0.03 1.04 0.00 1.00 0.99 0.03 1.02 0.04 0.994.8 1.00 0.06 1.06 0.00 1.00 0.99 0.05 1.04 0.04 0.994.9 1.00 0.10 1.11 0.00 1.00 0.99 0.09 1.09 0.04 1.005.0 1.00 0.17 1.20 0.00 1.00 0.99 0.15 1.16 0.04 1.005.1 1.00 0.31 1.44 0.00 1.00 0.99 0.23 1.28 0.05 1.005.2 1.00 0.46 1.86 0.01 1.00 0.98 0.33 1.46 0.05 1.005.3 0.75 0.61 1.92 0.01 1.00 0.98 0.44 1.75 0.06 1.005.4 0.75 0.74 2.94 0.01 1.00 0.95 0.56 2.17 0.07 1.005.5 0.75 0.85 5.11 0.02 1.00 0.93 0.67 2.82 0.09 1.005.6 0.75 0.93 10.05 0.03 1.00 0.89 0.77 3.87 0.12 0.995.7 0.75 0.96 18.38 0.06 1.00 0.88 0.84 5.56 0.17 0.995.8 0.75 0.98 37.57 0.12 1.00 0.86 0.89 8.13 0.23 0.995.9 0.75 0.99 72.00 0.20 1.00 0.80 0.93 11.00 0.29 0.996.0 0.75 1.00 172.80 0.38 1.00 0.75 0.95 16.05 0.37 0.996.1 0.75 1.00 287.99 0.50 1.00 0.73 0.97 23.96 0.47 0.996.2 0.75 1.00 432.01 0.60 1.00 0.67 0.98 31.92 0.54 0.996.3 - - - - - 0.63 0.99 53.90 0.67 0.996.4 - - - - - 0.59 0.99 73.56 0.73 0.986.5 0.75 1.00 863.98 0.75 1.00 0.54 0.99 102.93 0.79 0.986.6 - - - - - 0.49 1.00 151.15 0.85 0.986.7 0.50 1.00 575.99 0.67 1.00 0.46 1.00 165.79 0.86 0.986.8 - - - - - 0.43 1.00 254.03 0.90 0.986.9 - - - - - 0.39 1.00 255.03 0.90 0.987.0 - - - - - 0.35 1.00 288.24 0.91 0.987.1 0.50 1.00 1.00 1.00 0.34 1.00 313.94 0.92 0.987.5 - - - - - 0.29 1.00 474.78 0.95 0.978.0 - - - - - 0.23 1.00 379.82 0.93 0.978.4 - - - - - 0.20 1.00 664.69 0.96 0.979.0 - - - - - 0.16 1.00 1000.00 0.97 0.979.3 0.25 1.00 1.00 1.00 - - - - -9.4 - - - - - 0.13 1.00 868.17 0.97 0.9710.0 - - - - - 0.11 1.00 732.52 0.96 0.9710.4 - - - - - 0.11 1.00 705.39 0.96 0.9710.9 - - - - - 0.09 1.00 596.87 0.96 0.9711.5 - - - - - 0.06 1.00 1.00 0.9711.9 - - - - - 0.04 1.00 1.00 0.9712.4 - - - - - 0.03 1.00 1.00 0.9712.9 - - - - - 0.01 1.00 1.00 0.9613.5 - - - - - 0.01 1.00 1.00 0.9614.0 - - - - - 0.00 1.00 1.00 0.96

HbA1c threshold

Prediabetes (FPG), adolescents Prediabetes (FPG), adults

Sensitivity(True-positive

rate)

Specificity(True-negative

rate)

Positivelikelihood

ratio PPV NPV

Sensitivity(True-positive

rate)

Specificity(True-negative

rate)

Positivelikelihood

ratio PPV NPV

3.6 - - - - - 1.00 0.00 1.00 0.353.8 - - - - - 1.00 0.00 1.00 0.35 0.004.0 1.00 0.00 1.00 0.16 1.00 0.00 1.00 0.35 0.504.1 1.00 0.00 1.00 0.16 1.00 1.00 0.00 1.00 0.35 0.714.2 - - - - - 1.00 0.00 1.00 0.35 0.734.3 1.00 0.01 1.01 0.16 1.00 1.00 0.00 1.00 0.35 0.854.4 1.00 0.01 1.01 0.16 1.00 1.00 0.01 1.00 0.35 0.834.5 1.00 0.01 1.01 0.16 1.00 1.00 0.01 1.01 0.35 0.824.6 1.00 0.02 1.03 0.16 1.00 0.99 0.02 1.01 0.35 0.83

(continued )

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Table III. Continued

HbA1c threshold

Prediabetes (FPG), adolescents Prediabetes (FPG), adults

Sensitivity(True-positive

rate)

Specificity(True-negative

rate)

Positivelikelihood

ratio PPV NPV

Sensitivity(True-positive

rate)

Specificity(True-negative

rate)

Positivelikelihood

ratio PPV NPV

4.7 0.99 0.04 1.03 0.16 0.95 0.99 0.03 1.02 0.35 0.864.8 0.97 0.07 1.04 0.17 0.93 0.98 0.06 1.05 0.36 0.874.9 0.94 0.10 1.04 0.17 0.89 0.97 0.11 1.09 0.37 0.875.0 0.89 0.18 1.08 0.17 0.89 0.94 0.19 1.16 0.38 0.855.1 0.78 0.32 1.15 0.18 0.88 0.90 0.28 1.26 0.40 0.845.2 0.66 0.48 1.29 0.20 0.88 0.86 0.41 1.45 0.43 0.845.3 0.52 0.63 1.43 0.21 0.87 0.77 0.53 1.65 0.47 0.815.4 0.38 0.77 1.65 0.24 0.87 0.68 0.66 1.99 0.51 0.795.5 0.24 0.87 1.80 0.26 0.86 0.58 0.77 2.58 0.58 0.785.6 0.16 0.94 2.67 0.34 0.85 0.46 0.86 3.27 0.63 0.755.7 0.11 0.97 3.80 0.42 0.85 0.37 0.92 4.45 0.70 0.735.8 0.06 0.99 4.50 0.46 0.85 0.30 0.95 6.33 0.77 0.725.9 0.04 0.99 6.00 0.53 0.84 0.23 0.97 8.04 0.81 0.706.0 0.03 1.00 8.75 0.63 0.84 0.18 0.99 12.02 0.86 0.696.1 0.02 1.00 10.50 0.67 0.84 0.14 0.99 17.54 0.90 0.696.2 0.02 1.00 21.00 0.80 0.84 0.12 1.00 24.69 0.93 0.686.3 - - - - - 0.09 1.00 45.66 0.96 0.676.4 - - - - - 0.08 1.00 58.75 0.97 0.676.5 0.02 1.00 15.75 0.75 0.84 0.07 1.00 59.57 0.97 0.676.6 - - - - - 0.06 1.00 50.14 0.96 0.676.7 0.01 1.00 10.50 0.67 0.84 0.05 1.00 58.44 0.97 0.676.8 - - - - - 0.05 1.00 51.84 0.96 0.666.9 - - - - - 0.04 1.00 47.13 0.96 0.667.0 - - - - - 0.04 1.00 41.94 0.96 0.667.1 0.01 1.00 1.00 0.84 0.04 1.00 39.59 0.95 0.667.5 - - - - - 0.03 1.00 32.99 0.95 0.668.0 - - - - - 0.02 1.00 26.39 0.93 0.668.4 - - - - - 0.02 1.00 46.18 0.96 0.669.0 - - - - - 0.02 1.00 71.64 0.97 0.669.3 0.01 1.00 1.00 0.84 - - - - -9.4 - - - - - 0.01 1.00 60.33 0.97 0.6610.0 - - - - - 0.01 1.00 50.90 0.96 0.6610.4 - - - - - 0.01 1.00 49.02 0.96 0.6610.9 - - - - - 0.01 1.00 41.48 0.96 0.6611.5 - - - - - 0.01 1.00 1.00 0.6511.9 - - - - - 0.00 1.00 1.00 0.6512.4 - - - - - 0.00 1.00 1.00 0.6512.9 - - - - - 0.00 1.00 1.00 0.6513.5 - - - - - 0.00 1.00 1.00 0.6514.0 - - - - - 0.00 1.00 1.00 0.65

HbA1c threshold

Prediabetes (2-hr PG), adolescents Prediabetes (2-hr PG), adults

Sensitivity(true-positive

rate)

Specificity(true-negative

rate)

Positivelikelihood

ratio PPV NPV

Sensitivity(true-positive

rate)

Specificity(true-negative

rate)

Positivelikelihood

ratio PPV NPV

3.8 - - - - - 1.00 0.00 1.00 0.224.0 1.00 0.00 1.00 0.07 1.00 0.00 1.00 0.22 1.004.1 1.00 0.02 1.02 0.08 1.00 1.00 0.00 1.00 0.22 1.004.2 - - - - - 1.00 0.01 1.01 0.22 1.004.3 - - - - - 1.00 0.01 1.01 0.22 1.004.4 1.00 0.02 1.02 0.08 1.00 1.00 0.01 1.01 0.22 1.004.5 1.00 0.02 1.02 0.08 1.00 0.99 0.02 1.01 0.22 0.884.6 1.00 0.04 1.05 0.08 1.00 0.98 0.03 1.02 0.22 0.884.7 0.95 0.06 1.01 0.08 0.94 0.98 0.05 1.03 0.22 0.904.8 0.85 0.09 0.94 0.07 0.88 0.96 0.09 1.06 0.22 0.894.9 0.80 0.16 0.95 0.07 0.91 0.95 0.15 1.12 0.23 0.915.0 0.75 0.25 1.00 0.07 0.92 0.92 0.22 1.17 0.24 0.905.1 0.70 0.37 1.11 0.08 0.94 0.89 0.30 1.27 0.26 0.915.2 0.50 0.53 1.06 0.08 0.93 0.84 0.40 1.40 0.28 0.905.3 0.40 0.66 1.19 0.09 0.93 0.80 0.50 1.61 0.31 0.905.4 0.40 0.76 1.67 0.12 0.94 0.72 0.62 1.89 0.34 0.895.5 0.15 0.86 1.06 0.08 0.93 0.63 0.70 2.11 0.37 0.875.6 0.05 0.90 0.51 0.04 0.92 0.55 0.79 2.60 0.42 0.865.7 0.05 0.96 1.24 0.09 0.93 0.47 0.86 3.39 0.48 0.86

(continued )

THE JOURNAL OF PEDIATRICS www.jpeds.com Vol. 158, No. 6

952.e2 Lee et al

Table III. Continued

HbA1c threshold

Prediabetes (2-hr PG), adolescents Prediabetes (2-hr PG), adults

Sensitivity(true-positive

rate)

Specificity(true-negative

rate)

Positivelikelihood

ratio PPV NPV

Sensitivity(true-positive

rate)

Specificity(true-negative

rate)

Positivelikelihood

ratio PPV NPV

5.8 0.00 0.98 0.00 0.00 0.92 0.36 0.91 4.02 0.52 0.845.9 0.00 0.99 0.00 0.00 0.92 0.28 0.94 4.89 0.57 0.836.0 0.00 1.00 0.00 0.00 0.92 0.24 0.96 6.84 0.65 0.826.1 - - - - - 0.19 0.98 9.10 0.71 0.816.2 - - - - - 0.15 0.99 10.50 0.74 0.816.3 - - - - - 0.13 1.00 29.86 0.89 0.816.4 - - - - - 0.10 1.00 23.31 0.86 0.806.5 - - - - - 0.09 1.00 36.42 0.91 0.806.6 - - - - - 0.07 1.00 41.88 0.92 0.806.7 - - - - - 0.07 1.00 76.47 0.95 0.806.9 - - - - - 0.06 1.00 65.55 0.95 0.797.0 - - - - - 0.05 1.00 1.00 0.797.6 - - - - - 0.05 1.00 1.00 0.798.0 - - - - - 0.04 1.00 1.00 0.798.8 - - - - - 0.04 1.00 1.00 0.799.2 - - - - - 0.03 1.00 1.00 0.799.6 - - - - - 0.03 1.00 1.00 0.7910.0 - - - - - 0.02 1.00 1.00 0.7910.6 - - - - - 0.02 1.00 1.00 0.7911.2 - - - - - 0.01 1.00 1.00 0.7912.8 - - - - - 0.00 1.00 1.00 0.79

FPG, fasting plasma glucose; PPV, positive predictive value; NPV, negative predictive.At certain HbA1C thresholds, there were no individuals with those HbA1c values.

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Diagnosis of Diabetes using Hemoglobin A1c: Should Recommendations in Adults BeExtrapolated to Adolescents?

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Diagnosis of Diabetes using Hemoglobin A1c: Should Recommendations in Adults Be Extrapolated to Adolescents?MethodsResultsDiscussionReferences