Diabetes, Impaired Fasting Glucose, and Elevated HbA1c in U.S. Adolescents: The Third National Health and Nutrition Examination Survey
OBJECTIVE—Using population-based data, we estimated the prevalence of diabetes, impaired fasting glucose, and elevated HbA1c (>6%) levels in U.S. adolescents.
RESEARCH DESIGN AND METHODS—The Third National Health and Nutrition Examination Survey (1988–1994) examined a representative sample of the U.S. population, which included 2,867 adolescents aged 12–19 years who had serum glucose measured.
RESULTS—A total of 13 adolescents in the sample were considered to have diabetes; 9 reported using insulin, 2 reported using oral agents only, and 2 did not report any treatment but had high glucose levels (≥11.1 mmol/l regardless of length of fast or ≥7.0 mmol/l after an 8-h fast). Four of these cases (31% of the sample with diabetes) were considered to have type 2 diabetes. The estimated prevalence of diabetes (all types) per 100 adolescents ages 12–19 years was 0.41% (95% confidence interval 0–0.86). The prevalence of impaired fasting glucose (≥6.1 mmol/l) among adolescents without diabetes who had fasted for at least 8 h was 1.76% (0.02–3.50). The prevalence of elevated HbA1c (>6%) was 0.39% (0.04–0.74).
CONCLUSIONS—National data reflect the presence of type 2 diabetes in U.S. adolescents, but the survey sample size was not large enough to obtain precise prevalence estimates because of the relatively low prevalence.
Type 2 diabetes in adolescents may be on the rise in North America, especially among minority populations (1,2). Population-based studies have reported high prevalence estimates of type 2 diabetes in American-Indian adolescents (3,4), but such estimates are not available for other ethnic groups. Published data include clinical case series and therefore exclude undiagnosed cases and cases not referred to large pediatric centers (2). Cases have also been reported of adolescents with type 2 diabetes who were misclassified as having type 1 diabetes (2). Still, in large pediatric centers, diagnosed type 2 diabetes was recently reported to account for 8–45% of the new cases of diabetes (2). Thus, the true prevalence of type 2 diabetes (i.e., reported diagnosed and undiagnosed) might not lag far behind that of type 1 diabetes in adolescents. The reports of diagnosed cases of type 2 diabetes might also represent the tip of the iceberg of insulin resistance in the U.S. pediatric population.
In 1988–1994, the Third National Health and Nutrition Examination Survey (NHANES III) recruited a representative sample of U.S. adolescents aged 12–19 years who had serum glucose measured (5). We estimated the national prevalence of diabetes, impaired fasting glucose, and elevated HbA1c (>6%) levels in U.S. adolescents aged 12–19 years in 1988–1994.
RESEARCH DESIGN AND METHODS
NHANES III, which was conducted by the National Center for Health Statistics of the Centers for Disease Control and Prevention, comprised a probability sample of the U.S. civilian noninstitutionalized population selected by a complex multistage sampling design, with over-sampling of the black and Mexican-American populations (5). Adolescents were asked during a household interview to show the interviewer all of the medications they were taking. All medications related to diabetes were later coded as glucose regulators. At the subsequent examination, adolescents were asked if they were currently using insulin.
Each adolescent was randomly assigned to either a morning or an afternoon/evening examination session. Adolescents scheduled for a morning examination were instructed to fast at least 8 h, and those scheduled for an afternoon/evening examination session were instructed to fast at least 6 h. Adolescents known to be taking insulin were instructed not to fast before the examination. Serum glucose level was measured with a Hitachi Model 737 multichannel analyzer (Boehringer Mannheim, Indianapolis, IN) in participants >12 years of age as part of a standard battery of biochemical assessments (6). HbA1c was measured in whole blood with a Diamat automated high-performance liquid chromatography system (model 723; Bio-Rad Laboratories, Hercules, CA). The coefficients of variation were 0.8% for serum glucose and 1.73 and 1.57% for two HbA1c pools (6). BMI was calculated as weight in kilograms divided by height in meters-squared. BMI percentiles were calculated based on the Centers for Disease Control and Prevention growth charts and were age and sex specific (7).
The prevalence of diabetes was calculated for those adolescents who attended any physical examination and had glucose measured (n = 2,867). The prevalence of impaired fasting glucose was calculated for the subsample of adolescents who were assigned to the morning half-sample, attended a morning examination, and fasted for at least 8 h (n = 1,083). The prevalence of elevated HbA1c was calculated for all adolescents who attended any physical examination and had HbA1c measured (n = 2,852).
Adolescents were classified as having diagnosed diabetes if they reported using oral hypoglycemic agents or insulin. Adolescents were classified as having undiagnosed diabetes if they did not report using oral agents or insulin but they had a serum glucose value ≥11.1 mmol/l regardless of length of fast or a serum glucose value ≥7.0 mmol/l after a fast of 8 h or more (8). We considered adolescents on oral treatment only and adolescents with undiagnosed diabetes as having type 2 diabetes. Adolescents without diabetes who had fasting glucose ≥6.1 and <7.0 mmol/l were classified as having impaired fasting glucose (8). Adolescents without diabetes who had HbA1c >6%, which corresponds to the mean plus two standard deviations in this population, were classified as having elevated HbA1c.
SAS (9) was used for data management, and SUDAAN (10) was used to account for the complex sample design, to compare groups, and to compute appropriate standard errors for prevalence estimates. Separate weights were used for the entire examined sample and for the defined half-sample assigned to the morning examination session to account for the complex survey design, differential nonresponse, and planned oversampling (5). Thus, inferences may be made to the population of these ages in the U.S. in 1988–1994.
Of 3,234 adolescents aged 12–19 years, glucose was not measured for 367 and HbA1c was not measured for 240. Non-Hispanic white adolescents were more likely than non-Hispanic black adolescents to have HbA1c measured (94 vs. 90%, respectively, P = 0.009), and those with HbA1c measured were somewhat older than those without (mean age 15.9 vs. 15.6 years, respectively, P = 0.04). No other significant differences in sex, ethnicity, or overweight status were observed. Of the 1,166 adolescents with no insulin treatment who participated in the morning examination, were asked to fast for at least 8 h, and had glucose measured, 84 reported not fasting. Of the 2,858 adolescents with no insulin treatment who were asked to fast for at least 6 h and had glucose measured, 562 reported not fasting. In each of the two groups, age, sex, ethnicity, and overweight status were not statistically different between those who did and those who did not fast.
Of 2,867 adolescents who had glucose measured, 13 were classified as having diabetes (Table 1). Of these 13 adolescents, 9 reported using insulin and 2 were taking medications other than insulin. Two other adolescents who were not being treated for diabetes had glucose levels in the diabetic range (8.4 and 15.3 mmol/l); both had elevated HbA1c (8.4 and 10.0%) and high BMI (40.7 and 26.4 kg/m2 or 99th and 94th BMI percentile for age and sex). Of the 13 adolescents we classified as having diabetes, the 4 not using insulin (probable type 2 diabetes cases) were non-Hispanic black or Mexican-American.
Of the 1,083 adolescents who were assigned to and examined in a morning examination and fasted for at least 8 h, 20 had impaired fasting glucose and did not meet the criteria for diabetes (Table 2). Of the 2,852 adolescents who attended any examination and had HbA1c measurement, 22 had an HbA1c level >6% but did not meet the criteria for diabetes. Only 10 adolescents with HbA1c >6% had glucose measured in the morning sample and in the fasting stage. Only 3 of these 10 had both elevated HbA1c and impaired fasting glucose, all were from minority groups, and all had BMI >30 kg/m2 and the 97th percentile. Two adolescents had HbA1c >7% but did not meet the criteria for diabetes or impaired fasting glucose; one had a glucose level of 7.4 mmol/l measured in a nonmorning sample after fasting for only 6 h (BMI at the 59th percentile), and the other had a morning fasting glucose of 4.7 mmol/l (BMI at the 81st percentile).
Inferences to the U.S population were made using sampling weights. We estimated that the prevalences of diabetes, impaired fasting glucose (no diabetes), and elevated HbA1c (no diabetes) in the U.S population aged 12–19 years in 1988–1994 were, respectively, 0.41% (95% confidence interval [CI] 0–0.86), 1.76% (0.02–3.5), and 0.39% (0.04–0.74). Thus, we estimated that ∼100,000 U.S. adolescents had diabetes, 500,000 had impaired fasting glucose, and 100,000 had elevated HbA1c.
NHANES III data reflect the presence of type 2 diabetes in the pediatric population. Of the four adolescents considered to have type 2 diabetes, none were on insulin treatment; all four were members of minority groups, and all four had elevated BMI values. Two of these four cases were probably undiagnosed. On the other hand, no case of misclassification between type 1 and type 2 diabetes was suspected. In this small subsample, type 2 diabetes accounted for ∼31% of the cases of diabetes.
The numbers of cases of diabetes, impaired fasting glucose, and elevated HbA1c were small; the prevalence estimates of diabetes and impaired fasting glucose were low; and the CIs were large. For 2,867 adolescents tested for diabetes, 11 already knew they had diabetes, and only 2 had undiagnosed diabetes. For 1,083 adolescents without diabetes who fasted for at least 8 h, 20 had impaired fasting glucose, a risk factor for type 2 diabetes. The age group 12–19 (during or past puberty years) probably includes the pediatric age at highest risk for type 2 diabetes (2), and the design oversampled two minority populations at high risk. However, the sample size was not large enough to provide stable estimates in a general pediatric population with low prevalence. This contrasts with the usefulness of other population-based studies conducted in high-risk pediatric populations. Recent prevalence estimates for type 2 diabetes were 3.6% for Cree and Ojibway girls aged 10–19 living in Manitoba (3) and 5% (CI 3.2–6.9) for Pima Indians aged 15–19 living in Arizona (4). From 1966–1976 to 1987–1996, the prevalence increased fourfold for Pima Indian children aged 10 to 14 years and sixfold for children aged 15 to 19 years. Similarly, prevalence estimates for impaired fasting glucose were ∼3% for girls aged 15–19 years in Quebec (11), 3% for boys and 6% for girls aged 10–19 years in Ontario (12), and 2.7% for children aged 4–19 years in Saint Theresa Point in Manitoba (3).
Several features of our analysis should be underlined. First, NHANES III was undertaken between the years 1988 and 1994, and the increase in diagnosed pediatric type 2 diabetes reported in hospital case series was particularly noticeable after 1994 (2). Second, some data on treatment were self-reported, and omissions or misclassifications may have occurred. Third, it is also possible that a few more adolescents may have undiagnosed diabetes, but they may not have fasted for the time required for meeting the American Diabetes Association criteria (8). One adolescent had indeed a glucose level of 7.4 mmol/l and an HbA1c level of 7.1%, but we considered her as nondiabetic because she was scheduled for an afternoon/evening examination and only fasted for 6 h. However, there was little difference in age, sex, ethnicity, and BMI between the groups that did or did not fast or attend an examination.
The low prevalence of diabetes and impaired fasting glucose in U.S. adolescents whom we describe here by no means diminishes the public health importance of the emergence of type 2 diabetes in the pediatric population (2). Because the complications of diabetes are linked to duration, onset at an early age is likely to lead to increasing health problems early in adulthood. The disease has only recently been recognized and has probably recently increased in the general pediatric population. Because of the increasing prevalence of obesity, which has reached high levels in U.S. youth (13) and the expected population growth of minority groups (14), it is likely that the prevalence of type 2 diabetes in adolescents will also increase in the future, as it already has among American-Indian youth (1,2,3,4).
These data, despite their limitations, may raise questions on the respective values of HbA1c and impaired fasting glucose to identify adolescents at risk for type 2 diabetes. Adolescents with HbA1c >6% were somewhat likely to be non-Hispanic blacks and to have high BMI, which are risk factors for type 2 diabetes, and this was not as obvious for adolescents with impaired fasting glucose. Only three adolescents who reported fasting for at least 8 h had both elevated HbA1c and impaired fasting glucose. HbA1c has indeed been reported to be a good predictor of the later development of type 2 diabetes in Pima Indian children (M.M. Gabir and W.C. Knowler, personal communication) and is discussed as a screening test in adults (15). Further studies comparing HbA1c and random, fasting, or postload glucose levels in adolescents will be useful to develop strategies for screening or case findings for adolescents at risk for diabetes.
In conclusion, NHANES III data reveal the presence of type 2 diabetes in the U.S. pediatric population, but the prevalence of type 2 diabetes among U.S. adolescents appears to be quite low in 1988–1994. Because the prevalence is low, it is difficult to arrive at precise estimates of prevalence from surveys of the general population. At a time when the disease is emerging, other population-based approaches to ascertain incidence and prevalence, e.g., within more defined populations at higher risk of type 2 diabetes, may be required to identify trends in type 2 diabetes in adolescents. The Centers for Disease Control and Prevention recently embarked on a new research program to address this issue. Because type 2 diabetes may also represent the tip of the iceberg of insulin resistance in the U.S. pediatric population, studying impaired fasting glucose and other prediabetic conditions is also necessary.
Address correspondence and reprint requests to Jinan B. Saadine, Division of Diabetes Translation, Centers for Disease Control and Prevention, 4770 Buford Hwy, NE (MS-K68), Atlanta, GA 30341. E-mail:.
Received for publication 24 October 2000 and accepted in revised form 6 February 2001.
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