Adequate sample was available and valid HbA1c measurements were obtained from 14 069 (98%) of the 14 348 ARIC participants who attended Visit 2 and 99.9% of all people who provided a blood sample (n
= 14 082). In 2007–2008, we re-analyzed 383 of specimens that had been analyzed previously for HbA1c in 2003–2004 using the Tosoh 2.2 instrument (). Pearson's correlation between the measurements at the two time points was high (r
= 0.99), but with a slight bias: 0.29% higher HbA1c in 2007–2008 (Tosoh G7) compared with 2003–2004 (Tosoh 2.2; n
= 383 duplicate measurements; P
< 0.0001. The intraclass correlation (ICC) for the paired measurements was 0.98 (95% confidence interval (CI) 0.97–0.99) and a within-sample CV of 3.9% (95% CI 3.6%–4.2%) 11
. The high correlation between measurements and systematic bias is shown in and . Comparison of the two measurements yielded the following Deming regression equation: y(2007–2008 Tosoh G7)
= 0.073+1.034x(2003–2004 Tosoh 2.2)
Summary statistics comparing 2003–2004 and 2007–2008 HbA1c measurements (n = 383 pairs)
Comparison of 2003–2004 and 2007–2008 HbA1c (%) measurements performed using the Tosoh 2.2 and Tosoh G7 HPLC instruments (Tosoh Bioscience, South San Francisco, CA, USA), respectively (n = 383).
Figure 2 Bland-Altman plot of the difference in HbA1c (%) between values determined using the Tosoh G7 (Tosoh Bioscience, South San Francisco, CA, USA) minus those obtained using the Tosoh 2.2 compared against the mean. The solid line is the zero (reference) line, (more ...)
We compared the prevalence of undiagnosed diabetes using HbA1c values aligned to the different periods of measurement. With alignment of all ARIC HbA1c values to the 2003–2004 measurements obtained on the Tosoh 2.2 instrument, the prevalence of undiagnosed diabetes (HbA1c ≥6.5%) was 2.7%. After realignment to the 2007–2008 values obtained on the Tosoh G7 instrument, the prevalence of undiagnosed diabetes was 4.5%, a >60% increase in prevalence.
We used NHANES data to assess the comparability of our measurements in ARIC to nationally representative estimates of HbA1c in the general US population. Owing to systematic differences between 2003–2004 (Tosoh 2.2) and 2007–2008 (Tosoh G7), the above Deming regression equation was used to align the 2003–2004 ARIC measurements to the 2007–2008 (Tosoh G7) results. After calibration, ARIC measurements were similar to nationally representative data from a comparable population of adult participants in the NHANES (III, 1999–2004, and 2005–2006). Stratified results are shown in . The overall mean and median HbA1c levels in ARIC were 5.5% and 5.4%, respectively, similar to the mean and median values in NHANES III (5.4% and 5.4%, respectively) NHANES 1999–2004 (5.5% and 5.4%, respectively), and NHANES 2005–2006 (5.5% and 5.4%, respectively). Blacks and older people had consistently higher HbA1c values compared with Whites, but these differences were consistent across studies. Additional stratified analyses comparing the 5th, 25th, 75th, and 95th percentiles were similar (data not shown). NHANES III, conducted in 1988–1994, is the most contemporaneous to the ARIC HbA1c population (1990–1992). We compared the distribution of HbA1c in NHANES III and ARIC among participants who were aged 48–68 years, Black or White, and with no history of diabetes using overlayed kernal density plots (). These plots reveal a slightly more variable (wider) distribution among Blacks in NHANES III compared with ARIC, but almost completely overlapping distributions in Whites. Black participants in ARIC were only enrolled at the Jackson, Mississippi, and Forsyth County, North Carolina field sites. Thus, differences in the distribution of HbA1c comparing Blacks in ARIC with those in NHANES III may be the result of geographic differences and other related population characteristics. Nonetheless, overall measures of central tendency and the distributions of HbA1c in ARIC and NHANES surveys were similar, suggesting the comparability of ARIC measurements conducted using a modern state-of-the-art HPLC instrument to nationally representative data from the same era.
Table 3 Mean and median HbA1c (%) levels in non-Hispanic White and non-Hispanic Black participants without diagnosed diabetes or glucose-lowering medications, aged 48–68 years, in the Atherosclerosis Risk in Communities (ARIC) study and National Health (more ...)
Figure 3 Distributions of HbA1c in the Atherosclerosis Risk in Communities (ARIC) study (recalibrated; —) and the Third National Health and Nutrition Examination Survey (NHANES III; ------) overall (a), as well as in non-Hispanic Black (c) and White (b) (more ...)