IN BRIEF This abstraction letters achievement of A1C adjoin the articulate glucose altruism appraisal (OGTT) in admiration prediabetes amid ample and adipose African-American and Caribbean children. A attendant blueprint appraisal was completed for 230 children. Receiver operating adapted curves were generated to acquisition the predictive performances of altered tests adjoin the OGTT. A1C abandoned is a poor discriminator of prediabetes in our abstraction population, with low acuteness (70%) and specificity (48.8%). BMI z score, A1C, and homeostatic archetypal appraisal of insulin attrition are cogent predictors of prediabetes and, back taken together, accommodate bigger bigotry for prediabetes.
Obesity is on the acceleration common and has been declared as a all-around communicable (1). In 2011–2012, the prevalence of blubber was 16.9% in American adolescence (2). With an accretion accident of blubber amid children, bloom affliction providers charge admit and analyze comorbidities of blubber such as diabetes and prediabetes aboriginal in their development.
Prediabetes, about authentic as claret glucose concentrations college than accustomed but lower than diabetes thresholds, is a high-risk accompaniment for diabetes development. Evidence supports an affiliation amid prediabetes in adolescence and development of diabetes in adolescent adolescence (3). The prevalence of prediabetes amid adolescents is 16.1% and has been accretion (4).
Although there is accepted accord apropos the charge for diabetes screening in high-risk accouchement and adolescents, altercation persists apropos the best adapted screening methodologies. In 2009, an International Expert Committee recommended application A1C as a analytic apparatus for diabetes and prediabetes (5), which was accustomed by the American Diabetes Affiliation (ADA) in 2010 (6). Afore this, claret glucose appraisal was the absolute adjustment for diagnosing diabetes. One aloft limitation was that this change was based on epidemiological studies in the developed citizenry abandoned (7,8).
In 2017, ADA continues to acclaim diabetes screening application A1C, abnormally in those who are ample (BMI ≥85th percentile for age and ) with two of the afterward accident factors: 1) first- or second-degree about with blazon 2 diabetes, 2) boyhood race/ethnicity, 3) signs of insulin attrition (e.g., acanthosis nigricans) or altitude associated with insulin attrition (e.g., hypertension, dyslipidemia, polycystic ovary syndrome, small-for-gestational-age bearing weight), or 4) mother with diabetes or gestational diabetes during child’s evolution (9). Pediatricians accept followed this guideline by screening patients for prediabetes and diabetes application accidental measures such as A1C, amid others.
A1C measures nonenzymatic glycosylation of claret and can be acclimated anxiously for the assay of prediabetes and diabetes in adults as continued as the appraisal is accustomed by the National Glycohemoglobin Acclimation Program (NGSP) (www.ngsp.org), which standardizes >99% of the assays acclimated in the United States to the Diabetes Control and Complications Trial standard. Analytic belief for prediabetes accommodate an A1C of 5.7–6.4% (39–46 mmol/mol); a abnegation claret glucose (FPG) akin of 100–125 mg/dL (5.6–6.9 mmol/l), advertence broken abnegation glucose (IFG); or a 2-hour glucose akin of 140–199 mg/dL (7.8–11.0 mmol/l) during a 75-g articulate glucose altruism appraisal (OGTT), advertence broken glucose altruism (IGT) (9–11). According to ADA guidelines, the aforementioned belief administer to the pediatric citizenry (9).
The OGTT, which is advised the gold accepted for diagnosing prediabetes and diabetes, is accountable to limitations, including the charge for patients to be fasting. A1C, a accidental measurement, does not crave abnegation and is accordingly added convenient. A1C ethics are almost abiding afterwards accumulating (12) and reflect about 3 months of glycemia. A1C has been apparent to accept beneath day-to-day, as able-bodied as inter- and intra-subject airheadedness than claret glucose concentrations (13,14). However, admitting NGSP standardization, intra-subject variations in A1C after-effects accept been empiric amid adipose adolescence back application two altered NGSP-certified methodologies (15). Additionally, altitude involving aerial red claret corpuscle turnover, including hemoglobinopathies, anemia, pregnancy, contempo claret accident or transfusion, hemolysis, or erythropoietin use, baffle with the believability of A1C as a glycemic indicator (9).
Adult studies accept apparent that A1C is a acceptable augur of diabetes-related complications (16). However, studies in accouchement and adolescents accept approved that A1C has lower acuteness and specificity than OGTT in the assay of both prediabetes and diabetes (17). Nowicka et al. (18) approved that, amid accouchement and adolescents, A1C ethics amid 5.7 and 6.4% accept abandoned 47% acceding with OGTT, admitting A1C ≥6.5% accept 62% acceding with OGTT. Although the authors acclaimed that de-creasing the A1C beginning to 5.8% would advance the acuteness and specificity of A1C for anecdotic blazon 2 diabetes, they assured that A1C should not be acclimated abandoned for diagnosing prediabetes or diabetes. Similarly, Lee et al. (19) begin that the A1C absolute amount of 5.7% has abandoned 32% acuteness and 74% specificity for admiration dysglycemia (diabetes or prediabetes). These authors advocated application a accidental glucose akin of 100 or 110 mg/dL or a 1-hour glucose claiming appraisal amount of 110 or 120 mg/dL in analytic convenance because of the college predictive amount of these tests. In a middle-school cohort, Buse et al. (20) bent that A1C does not ascertain the aforementioned accumulation of adolescence with added diabetes accident as is authentic by IFG application the OGTT. Few studies in accouchement accept advised insulin attrition ambit and prediabetes predictors as bent by OGTT.
The aims of this abstraction are to actuate the affiliation amid A1C and prediabetes as authentic by OGTT and to analyze metaic ambit and anthropometric measures that are associated with prediabetes.
An institutional appraisal board–approved attendant blueprint appraisal was completed for accouchement and adolescents with a BMI at or aloft the 85th percentile for age and who were apparent in the pediatric endocrine annual at SUNY Downstate Medical Center and Kings County Hospital Center in the accomplished 10 years (January 2005 to August 2015). All patients had A1C and 2-h OGTT testing aural 3 months of the dispensary appointment date. BMI percentiles and z array were acquired based on 2000 Centers for Disease Control and Prevention advance archive (21). Patients with diabetes, anemia, or metformin use were excluded.
Study capacity were disconnected into two groups (prediabetes and normal) based on OGTT results. Homeostatic archetypal appraisal of insulin attrition (HOMA-IR) was affected application the blueprint (22):
FPG (mg/dL) × abnegation serum insulin (mU/L)/405
Area beneath the ambit (AUC) for glucose and insulin was affected by trapezoid rule.
ADA definitions for prediabetes were used. Prediabetes based on OGTT was authentic as IFG (FPG 100–125 mg/dL) or IGT (OGTT 2-h glucose 140–199 mg/dL), or both. Prediabetes based on A1C was authentic as an A1C amount alignment from 5.7 to 6.4%. Dyslipidemia was authentic as affair one of the afterward criteria: triglycerides ≥100 mg/dL (0–9 years of age) or ≥130 mg/dL (10–21 years), HDL cholesterol <40 mg/dL, LDL cholesterol ≥130 mg/dL, or absolute cholesterol ≥ 200 mg/dL (23).
A1C was abstinent by high-performance aqueous chromatography application Bio-Rad Variant II Turbo 2.0 (Bio-Rad Laboratories, Hercules, Calif.) connected per NGSP standards. Serum insulin levels were bent by electrochemiluminescence immunoassay on a Roche Modular E170 analyzer (Diamond Diagnostics, Holliston, Mass.) and on an ADVIA centaur XP arrangement (Siemens Medical Solutions, Malvern, Pa.). Claret glucose was bent by enzymatic UV appraisal (hexokinase method) on a Beckman coulter analyzer (AU2700 and AU5821 systems; Beckman Coulter, Indianapolis, Ind.) and hexokinase enzymatic adjustment (Roche modular E170).
Comparison of the two groups was performed with χ2, Mann-Whitney U, and t tests. The χ2 appraisal was acclimated to actuate an affiliation amid A1C and OGTT. Receiver operating adapted (ROC) curves were generated, and the breadth beneath the ROC ambit (AUC-ROC) was acclimated to actuate the achievement of predictors for prediabetes. Stepwise logistic corruption was acclimated to actuate predictors decidedly associated with prediabetes. P ethics <0.05 were advised statistically significant. Continuous variables are presented as agency and SD back commonly broadcast or medians and quartiles (25th–75th percentile) back variables are skewed.
A absolute of 301 archive were reviewed, of which 230 met the admittance criteria. Of the 230 capacity included in the study, 131 (57%) were changeable and 99 (43%) were male. A majority (83%) of capacity were of African-American or Caribbean descent. The ages of the abstraction capacity ranged from 6 to 21 years with a beggarly age of 13.5 ± 2.9 years. The beggarly A1C of the abstraction citizenry was 5.7 ± 0.5%. Sixty capacity (26%) were categorized as accepting prediabetes by OGTT, admitting 129 (56%) had an A1C ≥5.7%. The analytic and biochemical characteristics of the abstraction citizenry are apparent in Table 1.
Characteristics of the Abstraction Citizenry (n = 230)
Mean A1C was college in the accumulation with prediabetes than the accumulation with accustomed OGTT after-effects (5.89 ± 0.46 vs. 5.64 ± 0.47%, P = 0.0005). The prediabetic accumulation additionally had college AUC glucose, HOMA-IR, and 2-h insulin levels on OGTT. The two groups were not statistically altered with annual to BMI z score, lipid profile, AUC insulin, or abnegation insulin levels. Capacity in both groups were of agnate ages. The allegory of the two groups is apparent in Table 2. No cogent associations were begin amid prediabetes and , dyslipidemia, acanthosis nigricans, or ancestors history of diabetes, as apparent in Table 3.
Comparison of Accustomed OGTT to Prediabetic OGTT Group
Associations Amid Prediabetes and Categorical Variables
Of the 230 subjects, 18 met the OGTT prediabetes analogue only, 87 met the A1C prediabetes analogue only, 42 met both the definitions, and 83 had accustomed ethics for both OGTT and A1C. In comparing prediabetes detected by A1C belief to that detected by OGTT criteria, a cogent affiliation was begin amid the two tests (χ2 = 6.38, P = 0.0115) (Table 3).
The ROC ambit for A1C to ascertain prediabetes is apparent in Figure 1. The AUC-ROC was baby (0.64, 95% CI 0.56–0.72), which indicates that A1C achievement is poor in audition prediabetes with annual to OGTT. The A1C absolute of 5.7% had an estimated acuteness of 70% (95% CI 58–82%) and specificity of 48% (95% CI 41–56%) in audition prediabetes by OGTT. The sensitivities and specificities at anniversary A1C amount from 5.7 to 6.4% are apparent in Table 4.
ROC ambit for A1C in admiration prediabetes (OR 3.1, 95% CI 1.6–6.2, P = 0.001).
Sensitivity and Specificity of A1C Cut-Offs for Prediabetes
The AUC-ROC for HOMA-IR abandoned was additionally baby (0.61, 95% CI 0.52–0.71) (Figure 2).
ROC ambit for HOMA-IR in admiration prediabetes (OR 1.117, 95% CI 1.043–1.196, P = 0.002).
Stepwise corruption appraisal was performed with the afterward variables: BMI z score, A1C, HOMA-IR, ancestors history of diabetes, dyslipidemia, and attendance of acanthosis nigricans. Abandoned BMI z score, A1C, and HOMA-IR were begin to be decidedly associated with prediabetes afterwards adjusting for age and . Table 5 shows the estimated allowance ratios (ORs) for anniversary of the cogent predictors.
Predictors of Prediabetes From Stepwise Logistic Corruption Analysis
The ROC ambit for admiration prediabetes application the three cogent predictors acquired from stepwise corruption (BMI z score, A1C, and HOMA-IR) had bigger achievement with an AUC-ROC of 0.78 (95% CI 0.71–0.85) (Figure 3). The AUC-ROC for this archetypal was decidedly college than for the archetypal with A1C abandoned (P = 0.03) or HOMA-IR abandoned (P = 0.003).
ROC ambit for BMI z score, A1C, and HOMA-IR calm in admiration prediabetes.
This is one of the few studies evaluating A1C as a analytic apparatus for prediabetes in the pediatric population. We begin that A1C abandoned is a poor discriminator of prediabetes in ample and adipose accouchement of African-American and Caribbean descent.
The prevalence of prediabetes based on IFG or IGT in our abstraction citizenry was 26%. This aftereffect is constant with added studies advertisement a 12.3–28.0% prevalence of IFG or IGT amid U.S. overweight/obese accouchement and adolescents of altered ethnicities (24–26).
As apparent in antecedent studies, capacity with prediabetes had college HOMA-IR (27) and college 2-h claret insulin levels on OGTT (24), advertence a college amount of insulin resistance, which is a acclaimed forerunner of blazon 2 diabetes (28). This afresh speaks to the actuality that prediabetes is a high-risk accompaniment for development of diabetes, and medical absorption should be accustomed to individuals with prediabetes who accept signs and affection of insulin resistance, alike at a adolescent age.
The attendance of acanthosis nigricans on concrete assay has been appropriate to be a brand of hyperinsulinemia and insulin attrition (29–31). However, added studies accept begin no or basal affiliation amid acanthosis nigricans and insulin levels or insulin acuteness afterwards adjusting for age and adiposity in ample accouchement of altered ethnicities (32,33). African Americans, Native Americans, and Hispanics accept college ante of acanthosis nigricans compared to whites and Asians (29,34). A majority of capacity in our abstraction (85%) had acanthosis nigricans on concrete examination, which was not a cogent augur of prediabetes. The analytic use of acanthosis nigricans as an indicator of hyperinsulinemia is not conclusive.
Although the prediabetic accumulation had college A1C levels and A1C is acerb associated with OGTT results, back the A1C absolute of ≥5.7% was acclimated to ascertain prediabetes on OGTT, A1C achievement was poor. The AUC-ROC of A1C for audition prediabetes was low at 0.64, agnate to allegation of ahead appear studies. Nowicka et al. (18) acquired an AUC-ROC of 0.60 (95% CI 0.56–0.65) for A1C achievement with annual to IGT in accouchement and adolescents, and Lee et al. (19) appear an A1C AUC-ROC of 0.54 (95% CI 0.47–0.61) for admiration dysglycemia (prediabetes or diabetes) in adolescents (10–17 years of age).
A1C had poor acuteness over a ambit of absolute ethics for admiration prediabetes amid accouchement and adolescents in our study, which is agnate to the after-effects acquired from the National Bloom and Nutrition Assay Survey sample accomplice from 1999 to 2006 (17). The optimal A1C absolute for audition prediabetes in our abstraction citizenry was 5.7%, which had a almost aerial acuteness (70%) but low specificity (48%). The acuteness of a absolute amount of 5.7% to ascertain prediabetes was college in our abstraction than has been appear beforehand in accouchement (17,19). This could be attributed to differences in the indigenous composition of our abstraction citizenry compared to others. Non-Hispanic atramentous adults and accouchement are accepted to accept college A1C ethics than Mexican Americans and non-Hispanic whites (35,36).
A1C, HOMA-IR, and BMI z annual were the arch predictors of prediabetes in our abstraction subjects, afterwards adjusting for age and . Both college HOMA-IR and college A1C levels added the allowance of accepting prediabetes. Although BMI z array were not decidedly altered amid the prediabetic and accustomed OGTT groups, our after-effects showed that the college BMI z annual (OR = 0.39) decreased the allowance of accepting prediabetes, which is adverse to what we expected. This aberrant award may be the aftereffect of exclusion of capacity with diabetes, who are added acceptable to accept a college BMI z annual than capacity with prediabetes. All three of these predictors, back taken into annual together, provided bigger bigotry for prediabetes than A1C or HOMA-IR alone. Thus, A1C can be acclimated as a analytic apparatus to adumbrate prediabetes in accouchement back it is taken into annual with added analytic predictors of prediabetes. HOMA-IR, as a admeasurement of insulin resistance, is acclimated for analysis purposes and is not acclimated to analyze insulin attrition because of a abridgement of acclimation of insulin assays (37). At this time, we do not apostle application HOMA-IR for admiration prediabetes in adipose children.
Our abstraction has limitations. It is not accessible to absolutely exclude alternative bent in this attendant abstraction of adipose accouchement with a aerial boilerplate A1C of 5.7%, which is already in the prediabetes range, accustomed that OGTT usually was ordered back A1C was animated or back clinically indicated. In some cases, both A1C altitude and OGTT were done as allotment of the antecedent appraisal behindhand of antecedent class values, admitting in added cases, patients were referred to the endocrine dispensary for ahead animated A1C and appropriately the OGTT was ordered because of the ahead abstinent aberrant A1C. This ability accept acquired a accessible alternative or barometer bent consistent in an boilerplate A1C in the prediabetes ambit (5.7 ± 0.5%).
Additionally, the capacity in this abstraction had a akin background, so affliction charge be taken in generalizing the after-effects to a added accommodating population. However, this is one of the few studies comparing A1C to OGTT in an indigenous boyhood pediatric population.
We additionally accede the limitations of FPG and 2-h glucose testing in anecdotic prediabetes and diabetes because of the poor acceding (38) and abridgement of reproducibility of these tests (39,40). However, these were the gold accepted tests for assay of diabetes and prediabetes afore 2009, and no above markers accept been proposed.
Finally, this was a cross-sectional study, so approaching longitudinal studies in accouchement are bare to ascertain A1C cut-offs that adumbrate abiding morbidity.
A1C altitude has several advantages over added analytic methods, including that it is easier to access than an OGTT or altitude of abnegation serum markers. To analyze added accouchement at accident of developing diabetes, a accidental A1C can serve as a advantageous screening tool. However, A1C altitude abandoned should be acclimated with attention in accouchement and adolescents because of its low sensitivity. One may feel reassured afield with a accustomed A1C result. A complete analytic picture, including concrete assay findings, ancestors history, and added class parameters, should be taken into annual with the A1C amount back authoritative determinations about accident of diabetes and prediabetes. Repeating altitude of A1C may advance its sensitivity. Added studies are bare to validate reliable markers of prediabetes and diabetes in children.
A1C is a readily accessible screening apparatus for prediabetes and diabetes, but a accustomed A1C aftereffect should be interpreted with attention because of the low acuteness of this test. Additional testing, including echo A1C altitude and/or OGTT, may be useful. Relying on a ancient accustomed A1C amount may aftereffect in absent or delayed assay of prediabetes in accouchement and adolescents. Current markers acclimated in accouchement for prediabetes screening are not perfect, and added studies are needed. Aboriginal identification of accouchement with prediabetes can advice absolute all-important interventions against those at accomplished accident for developing diabetes in the future.
An articulate presentation of this abstraction was accustomed at the June 2016 ADA Scientific Sessions in New Orleans, La.
No abeyant conflicts of absorption accordant to this commodity were reported.
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