Predictors of Hemoglobin A1c in a National Sample of Nondiabetic Children
The Third National Health and Nutrition Examination Survey, 19881994
Kamal Eldeirawi1, and
Rebecca B. Lipton1,2
1 Division of Epidemiology and Biostatistics, School of Public Health, University of Illinois at Chicago, Chicago, IL.
2 Current affiliation: Section of Pediatric Endocrinology, Pritzker School of Medicine, University of Chicago, Chicago, IL.
Received for publication July 3, 2001; accepted for publication January 6, 2003.
 |
ABSTRACT
|
---|
Hemoglobin A1c (HbA1c) is related to glucose metabolism in diabetic and nondiabetic persons. Analysis of factors related to HbA1c may help researchers to better identify children with an increased likelihood of developing type 2 diabetes mellitus. In this study, the authors investigated predictors of HbA1c percentage among 1,700 Mexican-American, 1,787 African-American, and 1,441 non-Hispanic White young people aged 417.0 years who were free of diabetes and were examined in the Third National Health and Nutrition Examination Survey (19881994). HbA1c was positively related to age and body mass index (p = 0.065 and p = 0.008, respectively) and negatively related to an indicator of socioeconomic status, the poverty income ratio (p = 0.008). African Americans and Mexican Americans had higher mean HbA1c percentages than non-Hispanic Whites after data were controlled for age, sex, body mass index, maternal body mass index, and poverty income ratio. While some inconsistencies emerged, HbA1c was generally associated with other known risk factors for type 2 diabetes in young people. This report provides representative data on HbA1c percentage among nondiabetic children. However, further investigation will be needed to better understand the utility of HbA1c and its relation to type 2 diabetes in youth.
adolescence; adolescent medicine; body mass index; child; diabetes mellitus; ethnic groups; health surveys; hemoglobin A, glycosylated
Abbreviations:
Abbreviations: BMI, body mass index; HbA1c, hemoglobin A1c; NHANES III, Third National Health and Nutrition Examination Survey.
 |
INTRODUCTION
|
---|
The incidence and prevalence of type 2 diabetes mellitus are rapidly increasing in the United States, particularly among children and adolescents (13). Little is known about type 2 diabetes in children. The increase has been attributed, in part, to increasing obesity and overweight among children in the United States and in other parts of the world (4). Several studies have indicated that the prevalence of obesity among children and adolescents has increased alarmingly during recent years (514). Similarly, physical inactivity has been on the rise among children and adolescents in the United States (15).
Most children or adolescents diagnosed with type 2 diabetes mellitus in the United States are overweight, have a family history of type 2 diabetes, and display signs of insulin resistance. Type 2 diabetes is reported more frequently in females and in ethnic groups with increased risk (1618).
Early detection of diabetes may be crucial in reducing the impact of the disease among young people and their families. In addition, analysis of factors related to impaired glucose metabolism might lead to a better understanding of the current rise in type 2 diabetes among children. Hemoglobin A1c (HbA1c) is used as a quantitative measure of diabetes control among persons with diabetes (2628). Recently, assessment of HbA1c percentage has been suggested as an acceptable approach for diagnosing diabetes (1921) and for use as a screening tool for detecting type 2 diabetes in adults (2224) and children (25). In a follow-up study of older adults without diabetes, HbA1c was found to be significantly related to mortality from cardiovascular disease and ischemic heart disease among women but not among men, after data were controlled for possible confounders (29). HbA1c percentages were directly related to the risk of progression to diabetes mellitus among people with glucose intolerance (30).
Peters et al. (21) conducted a meta-analysis and obtained individual data from 11,276 subjects in 18 studies, for whom HbA1c percentages were measured concurrently with oral glucose tolerance tests, to determine whether HbA1c can be used in place of the oral glucose tolerance test to diagnose diabetes. The study showed that almost 90 percent of patients with an HbA1c percentage higher than 7 percent could be classified as having diabetes using the oral glucose tolerance test.
Race/ethnicity has been shown to be significantly related to HbA1c among people with diabetes, people with "borderline diabetes," and people without diabetes. Among persons with diabetes, African Americans were found to have a higher mean HbA1c percentage than non-Hispanic Whites (26). HbA1c was measured for 254 nondiabetic sixth- and seventh-grade schoolchildren and was found to be higher among minority children at increased risk of type 2 diabetes than among non-Hispanic White children (25).
According to Fagot-Campagna et al. (31), among adolescents aged 1219 years who were examined in the Third National Health and Nutrition Examination Survey (NHANES III), the prevalence of type 2 diabetes was 4.1 per 1,000 (95 percent confidence interval: 0, 8.6); the prevalence of elevated (>6 percent) HbA1c was 3.9 per 1,000 (95 percent confidence interval: 0.4, 7.4); and the prevalence of an impaired fasting glucose level was 17.6 per 1,000 (95 percent confidence interval: 0.2, 35.0). Adolescents with an increased HbA1c percentage were more likely to be African Americans with a high body mass index (BMI).
The objective of this article was to identify predictors of HbA1c among 4,928 nondiabetic young people who were examined in NHANES III.
 |
MATERIALS AND METHODS
|
---|
This analysis was based on data from NHANES III, which was carried out in 19881994. Sampling and laboratory methods have been described elsewhere (32, 33). The sample used in this analysis included 4,928 persons aged 417.0 years. Pregnant women (n = 14), persons on insulin (n = 8) or oral hypoglycemic agents (n = 1), and those not designated as African-American, Mexican-American, or non-Hispanic White (n = 306) were excluded from the sample. There were no subjects with undiagnosed diabetes included in the sample examined for this study (persons aged 4.017.0 years).
Statistical analyses were conducted using SAS, version 8.0 (SAS Institute, Inc., Cary, North Carolina). This version of SAS has new features (PROC SURVEYMEANS and SURVEYREG) that account for complex sample designs. Appropriate sampling weights were used for all analyses. Individuals with missing values for any of the variables included in the final analysis were excluded. The dependent variable was HbA1c.
The independent variables included age (in years) at physical examination, race/ethnicity, sex, BMI (weight (kg)/height (m)2), maternal BMI, and poverty income ratio. Poverty income ratio was used as an indicator of socioeconomic status. It is the ratio of a familys income to the poverty threshold of a family of the same size for the same calendar year. Maternal BMI was used as a crude measure of familial, genetic, and environmental factors. Univariate and multivariate linear regression analyses were performed for assessment of the relation between HbA1c percentage and the independent variables. Three categories were defined for each of the continuous independent variables: age, poverty income ratio, BMI, and maternal BMI. Unadjusted as well as adjusted mean HbA1c percentages were calculated from linear regression models treating these categories as dummy variables. Then, treating age, poverty income ratio, BMI, and maternal BMI as continuous variables, separate models were created for six sex-race/ethnicity categories. Finally, analyses were conducted for four age categories and eight age-sex categories. Several interaction terms were examined but were not found to be significant; thus, they were not included in the final models. No corrections were made for multiple comparisons.
 |
RESULTS
|
---|
The sample consisted of 1,700 Mexican-American, 1,787 African-American, and 1,441 non-Hispanic White children who completed the medical examination; 49.3 percent were males. African Americans and Mexican Americans were overrepresented in the sample, because NHANES III was designed to oversample these two ethnic groups. The weighted mean age of the children studied was 10.72 years. Characteristics of the sample and the weighted mean values of the variables used in the analysis are given in table 1.
View this table:
[in this window]
[in a new window]
|
TABLE 1. Characteristics of 4,928 children aged 417.0 years who participated in the Third National Health and Nutrition Examination Survey, 19881994
|
|
Non-Hispanic Whites were older at the time of examination, had a higher mean poverty income ratio, and had lower values for HbA1c, BMI, and maternal BMI than African Americans and Mexican Americans. The highest BMI and maternal BMI were observed among Mexican Americans.
Sex was significantly associated with HbA1c percentage (table 2). A regression analysis treating age, BMI, maternal BMI, and poverty income ratio as continuous variables showed that age was marginally related to HbA1c (p = 0.065). Mean HbA1c percentage increased with age among children in the first four age quintiles (ages 4.0013.50 years) and declined in the fifth quintile (ages 13.5117.00 years) (figures 1, 2, and 3). This was true for African-American males and for females of all three ethnic groups, while among non-Hispanic White and Mexican-American males, a more linear association of HbA1c with age was apparent. HbA1c was positively associated with BMI (figure 4) and negatively associated with poverty income ratio (figure 5); p values for trend were 0.15 and 0.001 for BMI and poverty income ratio, respectively. However, after data were controlled for age, sex, and race/ethnicity, this relation became insignificant.
View this table:
[in this window]
[in a new window]
|
TABLE 2. Crude and adjusted weighted mean hemoglobin A1c percentages among 4,928 children aged 417.0 years, Third National Health and Nutrition Examination Survey, 19881994
|
|

View larger version (9K):
[in this window]
[in a new window]
|
FIGURE 1. Weighted mean hemoglobin A1c (HbA1c) percentage by quintile of age (in years) among all children aged 417.0 years, Third National Health and Nutrition Examination Survey, 19881994.
|
|

View larger version (13K):
[in this window]
[in a new window]
|
FIGURE 2. Weighted mean hemoglobin A1c (HbA1c) percentage by quintile of age (in years) and race/ethnicity among male children aged 417.0 years, Third National Health and Nutrition Examination Survey, 19881994.
|
|

View larger version (14K):
[in this window]
[in a new window]
|
FIGURE 3. Weighted mean hemoglobin A1c (HbA1c) percentage by quintile of age (in years) and race/ethnicity among female children aged 417.0 years, Third National Health and Nutrition Examination Survey, 19881994.
|
|

View larger version (11K):
[in this window]
[in a new window]
|
FIGURE 4. Crude and adjusted weighted mean hemoglobin A1c (HbA1c) percentages by quintile of body mass index (weight (kg)/height (m)2) among children aged 417.0 years, Third National Health and Nutrition Examination Survey, 19881994.
|
|

View larger version (11K):
[in this window]
[in a new window]
|
FIGURE 5. Crude and adjusted weighted mean hemoglobin A1c (HbA1c) percentages by quintile of poverty income ratio among children aged 417.0 years, Third National Health and Nutrition Examination Survey, 19881994.
|
|
In the multivariate analysis, maternal BMI was significantly associated with HbA1c after BMI was accounted for. However, after data were controlled for age, sex, and race/ethnicity, neither BMI nor maternal BMI was related to HbA1c. African Americans and Mexican Americans had higher mean HbA1c percentages than non-Hispanic Whites after data were controlled for age, sex, BMI, maternal BMI, and poverty income ratio. Females had a significantly lower HbA1c percentage than males after other potentially confounding variables in the model were accounted for (table 2).
Separate regression models were constructed for each ethnic group. After data were controlled for BMI and maternal BMI, age, and poverty income ratio, sex was related to HbA1c only among non-Hispanic Whites, with females having significantly lower mean HbA1c percentages than males. BMI was significantly associated with HbA1c among African Americans and Mexican Americans but not among non-Hispanic Whites after maternal BMI, age, sex, and poverty income ratio were accounted for. When further analyses were performed, BMI was associated with HbA1c among African-American males and Mexican-American females only (table 3).
View this table:
[in this window]
[in a new window]
|
TABLE 3. Regression coefficients (ß) from multivariate linear models predicting hemoglobin A1c percentage among children aged 417.0 years, by race/ethnicity and sex, Third National Health and Nutrition Examination Survey, 19881994
|
|
When analyses were performed separately in the four age strata, African Americans maintained a significantly higher HbA1c percentage than did non-Hispanic Whites. Among persons aged 1517.0 years, HbA1c was significantly higher in African Americans and Mexican Americans than in non-Hispanic Whites. In the same age category, females had significantly lower HbA1c percentages than males. When the age categories were further stratified by sex, BMI was significantly associated with HbA1c among males aged 1014 years and among females aged 1517.0 years (table 4).
View this table:
[in this window]
[in a new window]
|
TABLE 4. Regression coefficients (ß) from multivariate linear models predicting hemoglobin A1c percentage among children aged 417.0 years, by sex and age group, Third National Health and Nutrition Examination Survey, 19881994
|
|
 |
DISCUSSION
|
---|
The results of this study confirm previous findings (25) that race/ethnicity influences HbA1c percentage even among healthy children. In the univariate analyses, many of the demographic and anthropometric variables studied were related to HbA1c. However, when race/ethnicity was taken into account, most of these relations became insignificant.
Rates of type 2 diabetes mellitus are higher among African Americans and Mexican Americans than among non-Hispanic Whites in the United States (3438). Most cases of type 2 diabetes in children have been reported from minority populations (1618). This analysis indicated that mean HbA1c percentages were higher among nondiabetic African-American and Mexican-American young people than among non-Hispanic Whites. We found that BMI was related to HbA1c percentage among African-American and Mexican-American children but not among Whites after data were controlled for maternal BMI, age, sex, and poverty income ratio.
Although socioeconomic factors are thought to influence type 2 diabetes risk, poverty income ratio was not strongly related to HbA1c in these data, after the data were controlled for race/ethnicity. The three ethnic groups varied significantly with regard to poverty income ratio, which suggests that poverty income ratio may serve as a proxy for socioeconomic status, even if it is a relatively poor indicator. However, the question of whether race/ethnicity is a proxy for socioeconomic status remains and has been actively debated in the literature. Race is clearly a social rather than a biologic or physiologic variable (39), and data show that socioeconomic status accounts for many of the observed disparities in health across racial groups (40). In the current study, poverty income ratio differed significantly by race/ethnicity, so we tried to control for it in the analysis. However, if poverty income ratio is not a good indicator of socioeconomic status, controlling for it may not have totally eliminated the effect of socioeconomic status.
It has also been observed that ethnic and racial differences persist even after socioeconomic status has been accounted for (40). The ethnic differences in these data may reflect the increased risk of diabetes among US minority groups, a finding in line with other reports that most children with type 2 diabetes are from minority populations (1618).
Our findings had some design and measurement limitations. Data obtained from NHANES III are cross-sectional and thus limit our ability to draw conclusions about causal factors; further longitudinal studies are warranted. In this study, poverty income ratio, an imperfect measure of socioeconomic status, was used. A combination of variables is likely to reflect socioeconomic status more effectively. Furthermore, using BMI as a measure of adiposity to compare children across various age and racial/ethnic groups might not be optimal, since racial disparity in adiposity is likely to be linked to pubertal maturation (41).
NHANES III was a comprehensive national survey that collected data on a wide range of variables. The survey, by design, oversampled African Americans and Mexican Americans, thereby including large numbers of minority children. NHANES III provided the first representative data (albeit cross-sectional in nature) on HbA1c percentage among nondiabetic children. These findings point to the need to collect longitudinal data to further understand the utility of HbA1c among youth and its relation to type 2 diabetes risk.
 |
NOTES
|
---|
Correspondence to Kamal M. Eldeirawi, Epi/Bio (MC 923), School of Public Health, University of Illinois at Chicago, 1603 West Taylor Street, Room 912, Chicago, IL 60612-7260 (e-mail: keldei1{at}uic.edu). 
 |
REFERENCES
|
---|
- Fagot-Campagna A. Type 2 diabetes among North American children and adolescents: an epidemiologic review and a public health perspective. J Pediatr 2000;136:66472.[CrossRef][ISI][Medline]
- Rosenbloom AL, Joe JR, Young RS, et al. Emerging epidemic of type 2 diabetes in youth. Diabetes Care 1999;22:34554.[Abstract]
- Trends in the prevalence and incidence of self-reported diabetes mellitusUnited States, 19801994. MMWR Morb Mortal Wkly Rep 1997;46:101418.[Medline]
- American Diabetes Association. Type 2 diabetes in children and adolescents. Diabetes Care 2000;23:3819.[Free Full Text]
- Kuczmarski RJ, Flegal KM, Campbell SM, et al. Increasing prevalence of overweight among US adults: The National Health and Nutrition Examination Surveys, 1960 to 1991. JAMA 1994;272:20511.[Abstract]
- Flegal KM, Troiano RP. Changes in the distribution of body mass index of adults and children in the US population. Int J Obes Relat Metab Disord 2000;24:80718.[CrossRef][Medline]
- Chu NF. Prevalence and trends of obesity among school children in TaiwanThe Taipei Children Heart Study. Int J Obes 2001;25:1706.[CrossRef][ISI]
- Ogden CL, Troiano RP, Briefel RR, et al. Prevalence of overweight among preschool children in the United States, 1971 through 1994. Pediatrics 1997;99:E1.[Medline]
- de Onis M, Blossner M. Prevalence and trends of overweight among preschool children in developing countries. Am J Clin Nutr 2000;72:10329.[Abstract/Free Full Text]
- Moreno LA, Sarria A, Fleta J, et al. Trends in body mass index and overweight prevalence among children and adolescents in the region of Aragon (Spain) from 1985 to 1995. Int J Obes Relat Metab Disord 2000;24:92531.[CrossRef][Medline]
- Prevalence of overweight among third- and sixth-grade childrenNew York City, 1996. MMWR Morb Mortal Wkly Rep 1998;47:9804.[Medline]
- Johnson-Down L, OLoughlin J, Koski KG, et al. High prevalence of obesity in low income and multiethnic schoolchildren: a diet and physical activity assessment. J Nutr 1997;127:231015.[Abstract/Free Full Text]
- Prevalence of overweight among adolescentsUnited States, 198891. MMWR Morb Mortal Wkly Rep 1994;43:81821.[Medline]
- Troiano RP, Flegal KM, Kuczmarski RJ, et al. Overweight prevalence and trends for children and adolescents: The National Health and Nutrition Examination Surveys, 1963 to 1991. Arch Pediatr Adolesc Med 1995;149:108591.[Abstract]
- Fagot-Campagna A, Burrows NR, Williamson DF. The public health epidemiology of type 2 diabetes in children and adolescents: a case study of American Indian adolescents in the southwestern United States. Clin Chim Acta 1999;286:8195.[CrossRef][ISI][Medline]
- Fagot-Campagna A. Emergence of type 2 diabetes mellitus in children: epidemiological evidence. J Pediatr Endocrinol Metab 2000;13(suppl 6):1395402.[ISI][Medline]
- Fagot-Campagna A, Pettitt DJ, Engelgau MM, et al. Type 2 diabetes among North American children and adolescents: an epidemiologic review and a public health perspective. J Pediatr 2000;136:66472.[CrossRef][ISI][Medline]
- Dabelea D, Pettitt DJ, Jones KL, et al. Type 2 diabetes mellitus in minority children and adolescents: an emerging problem. Endocrinol Metab Clin North Am 1999;28:70929, viii.[ISI][Medline]
- Medow MA. Use of glycosylated hemoglobin levels for diagnosing diabetes mellitus. (Letter). JAMA 1997;277:211.
- Little RR, England JD, Wiedmeyer HM, et al. Glycated haemoglobin predicts progression to diabetes mellitus in Pima Indians with impaired glucose tolerance. Diabetologia 1994;37:2526.[CrossRef][ISI][Medline]
- Peters AL, Davidson MB, Schriger DL, et al. A clinical approach for the diagnosis of diabetes mellitus: an analysis using glycosylated hemoglobin levels. Meta-analysis Research Group on the Diagnosis of Diabetes Using Glycated Hemoglobin Levels. JAMA 1996;276:124652.[Abstract]
- Rohlfing CL, Little RR, Wiedmeyer HM, et al. Use of GHb (HbA1c) in screening for undiagnosed diabetes in the U.S. population. Diabetes Care 2000;23:18791.[Abstract]
- Hanson RL, Nelson RG, McCance DR, et al. Comparison of screening tests for non-insulin-dependent diabetes mellitus. Arch Intern Med 1993;153:213340.[Abstract]
- Little RR, England JD, Wiedmeyer HM, et al. Relationship of glycosylated hemoglobin to oral glucose tolerance: implications for diabetes screening. Diabetes 1988;37:604.[Abstract]
- Wollitzer AO, Giammattei J, Jovanovic L, et al. HbA1c as a potential screening test for childhood type 2 diabetes mellitus. (Abstract). Diabetes 2001;50(suppl 2):A227.
- Eberhardt MS, Lackland DT, Wheeler FC, et al. Is race related to glycemic control? An assessment of glycosylated hemoglobin in two South Carolina communities. J Clin Epidemiol 1994;47:11819.[ISI][Medline]
- Dorchy H, Roggemans MP, Willems D. Glycated hemoglobin and related factors in diabetic children and adolescents under 18 years of age: a Belgian experience. Diabetes Care 1997;20:26.[Abstract]
- Niketic V, Djurdjic V, Stojkovic V, et al. Glycated hemoglobin in hypoglycemia. Clin Chim Acta 1989;180:1218.[CrossRef][ISI][Medline]
- Park S, Barrett-Connor E, Wingard DL, et al. GHb is a better predictor of cardiovascular disease than fasting or postchallenge plasma glucose in women without diabetes: The Rancho Bernardo Study. Diabetes Care 1996;19:4506.[Abstract]
- Yoshinaga H, Kosaka K. High glycosylated hemoglobin levels increase the risk of progression to diabetes mellitus in subjects with glucose intolerance. Diabetes Res Clin Pract 1996;31:719.[CrossRef][ISI][Medline]
- Fagot-Campagna A, Saaddine JB, Flegal KM, et al. Diabetes, impaired fasting glucose, and elevated HbA1c in U.S. adolescents: The Third National Health and Nutrition Examination Survey. Diabetes Care 2001;24:8347.[Abstract/Free Full Text]
- National Center for Health Statistics. Plan and operation of the Third National Health and Nutrition Survey, 198894. Hyattsville, MD: National Center for Health Statistics, 1994.
- Gunter EW, Lewis BG, Koncikowski SM. Laboratory procedures used for the Third National Health and Nutrition Examination Survey (NHANES III), 19881994. Atlanta, GA: National Center for Environmental Health, Centers for Disease Control and Prevention, 1996.
- Carter JS, Pugh JA, Monterrosa A. Non-insulin-dependent diabetes mellitus in minorities in the United States. Ann Intern Med 1996;125:22132.[Abstract/Free Full Text]
- Marshall JA, Hamman RF, Baxter J, et al. Ethnic differences in risk factors associated with the prevalence of non-insulin-dependent diabetes mellitus: The San Luis Valley Diabetes Study. Am J Epidemiol 1993;137:70618.[Abstract]
- Cowie CC, Harris MI, Silverman RE, et al. Effect of multiple risk factors on differences between blacks and whites in the prevalence of non-insulin-dependent diabetes mellitus in the United States. Am J Epidemiol 1993;137:71932.[Abstract]
- Mitchell BD, Stern MP. Recent developments in the epidemiology of diabetes in the Americas. World Health Stat Q 1992;45:3479.[Medline]
- Harris MI. Noninsulin-dependent diabetes mellitus in black and white Americans. Diabetes Metab Rev 1990;6:7190.[ISI][Medline]
- LaVeist TA. On the study of race, racism, and health: a shift from description to explanation. Int J Health Serv 2000;30:21719.[ISI][Medline]
- Williams DR. Race, socioeconomic status, and health: the added effects of racism and discrimination. Ann N Y Acad Sci 1999;896:17388.[Abstract/Free Full Text]
- Kimm SY, Barton BA, Obarzanek E, et al. Racial divergence in adiposity during adolescence: The NHLBI Growth and Health Study. Pediatrics 2001;107:E34.[Medline]