Applying A1C criteria to define undiagnosed diabetes (≥6.5%) and high risk of diabetes (6.0 to <6.5%), we find that in the U.S. population aged ≥20 years during 2003–2006, the crude prevalence of total diabetes is 9.6% or 20.4 million, of which 19.0% is undiagnosed (7.8% previously diagnosed and 1.8% undiagnosed). An additional 3.5% of adults, or 7.4 million, are at high risk of diabetes, yielding 13.0% of the U.S. population aged ≥20 years, or 27.8 million, who have a hyperglycemic condition. Prevalence of these conditions is strongly influenced by increasing age. While we find no differences by sex, we continue to find non-Hispanic blacks and Mexican Americans disproportionately affected. Although the prevalence of previously diagnosed diabetes has significantly increased over time in most population groups, the proportion of diabetes that is undiagnosed using A1C criteria has significantly decreased over time in many groups, and the proportion at high risk of diabetes has significantly decreased in almost all groups.
A1C criteria result in substantially lower prevalences of undiagnosed and total diabetes, and being at high risk for diabetes, than prevalences estimated from fasting plasma glucose or 2-h glucose. The prevalences reported here can be compared with our recently reported prevalences of undiagnosed diabetes, impaired fasting glucose (IFG), and impaired glucose tolerance (IGT) in 2005–2006 using glucose criteria (8
) (online appendix Table A1, available at http://care.diabetesjournals.org/cgi/content/full/dc09-1524/DC1
). Standardized prevalence of undiagnosed diabetes using A1C criteria (1.8%) in this report was one-third that using either FPG or 2-h glucose criteria (5.0% combined, 2.4% by FPG alone, and 4.8% by 2-h alone), resulting in a prevalence of total diabetes using A1C criteria one-quarter less than that of total diabetes using either glucose criteria (9.3 vs. 12.6%). The proportion of total diabetes that is undiagnosed using A1C criteria (21.5%) was 40% less than that using glucose criteria (34.2%). The prevalence of being at high risk of diabetes using A1C criteria (3.4%) was dramatically reduced to about one-tenth the prevalence using FPG/2-h glucose criteria (29.0% combined, 25.2% IFG, and 13.6% IGT).
The substantially lower prevalence of diabetes detected by A1C criteria was illustrated () by analyzing the concordance of A1C, FPG, and 2-h glucose criteria in 2005–2006. A1C detected only 30% of undiagnosed diabetes defined by any of the three criteria; by contrast, 2-h plasma glucose detected 90% of undiagnosed diabetes. A relatively large proportion (19%) of undiagnosed diabetes was detected by both FPG and 2-h glucose but not by A1C.
The fact that prevalence of being at high risk for diabetes/pre-diabetes detected by A1C is about one-tenth the prevalence of IFG or IGT is striking. The relatively small sample size during 2005–2006 prohibited our assessing discordance of prevalence at high risk for diabetes using A1C versus prevalence of pre-diabetes, undiagnosed diabetes, and normal glucose status using glucose criteria, because of the large number of overlapping categories involved.
Certain relationships by age and race/ethnicity also differed between results based on A1C criteria (herein) and glucose criteria (8
) (online appendix Table A1). By age, undiagnosed diabetes increased less dramatically using A1C criteria than it did using glucose criteria, whereas prevalence of being at high risk for diabetes increased relatively more dramatically using A1C criteria. Factors unrelated to glycemic control may explain some of the increase by age in prevalence of high risk for diabetes. A1C increased with age in nondiabetic participants of the Framingham Offspring Study and the NHANES 2001–2004 and in the Framingham Offspring Study participants with normal glucose tolerance, while adjusting for fasting and 2-h glucose levels and other factors (9
). Racial/ethnic differences in the prevalence of undiagnosed diabetes and high risk of diabetes were disproportionately greater using A1C criteria compared with glucose criteria, which may also be explained in part by factors unrelated to glucose control. Blacks and Hispanics with IGT in the Diabetes Prevention Program had higher A1C levels than whites, after adjusting for glucose levels and other factors such as age, sex, education, blood pressure, BMI, hematocrit, and insulin resistance (10
). This may suggest that hemoglobin glycation or red cell survival differs among racial/ethnic groups.
A limitation of our analyses is that determination of undiagnosed diabetes and high risk for diabetes/pre-diabetes is based on a single measurement of A1C, FPG, and 2-h glucose from subjects who self-reported that they fasted appropriately (for FPG and 2-h glucose), whereas retesting is suggested for diagnosis in a clinical setting. Consequently, some prevalence estimates may be overstated (11
). In addition, although there should be limited interference from hemoglobin traits due to the A1C assay methods used in NHANES (2
), A1C levels may be spurious with conditions that change red cell turnover (e.g., anemia) (12
) regardless of the assay method used.
Some individuals with self-reported diabetes may not have had diabetes detected if A1C criteria had been used. When we excluded individuals self-reporting diabetes who reported not using glycemic medications and who had A1C <6.5%, prevalence of diagnosed diabetes decreased 0.9%. This was a larger decrease than when we performed the same analysis excluding those with FPG <126 mg/dl (0.3% decrease) or those with 2-h glucose <200 mg/dl (0.2% decrease). Consequently, our estimates of diagnosed and total diabetes may be overstated, and the percent of total diabetes that is undiagnosed may be understated.
The international expert committee emphasized that glucose and A1C levels reflect different aspects of glucose metabolism. The purpose of their report was not to establish identical prevalences in defining new criteria for diabetes and high risk for diabetes but rather to identify individuals at risk for diabetes complications and diabetes so that preventive treatment could follow. It will be important to determine longitudinally whether complication rates differ between individuals detected by glucose criteria or by A1C criteria.
If A1C criteria are adopted by the American Diabetes Association, the identification of a smaller high-risk group may be considered advantageous because of the limited availability of resources. However, a substantial proportion of individuals similar to those in the Diabetes Prevention Program (14
) would be missed and not receive preventive intervention to reduce risk. The nearly 1% of the population previously diagnosed with diabetes who no longer have diabetes by A1C criteria may need careful explanation of the alternative diagnostic criteria, the arbitrary cut point for diagnosis along a continuum of risk, and the progressive nature of dysglycemia so that diabetic/pre-diabetic conditions are not thought to be less real or serious. While the change in diagnosis in some from diabetes to high risk of diabetes using A1C criteria might not alter recommended glycemic control and lifestyle management, recommended blood pressure and lipid targets would differ (15
), requiring careful consideration of individualized therapeutic goals.
A change to A1C criteria would also impact national surveillance of these conditions. Estimated self-reported diabetes based on surveys and the tracking of temporal trends would likely be difficult to interpret for some time before these criteria are fully assimilated in medical practice. An interim period of measurement both by A1C and glucose may be necessary for international and domestic historical comparisons.
The potential impact of these dramatically lower estimates of diabetes, and particularly of high risk for diabetes, on public perception of the magnitude and seriousness of diabetes is concerning. The fact remains that diabetes and its sequelae are devastating and escalating public health problems that disproportionately affect the elderly, non-Hispanic blacks, and Mexican Americans. A continued commitment to the primary and secondary prevention of diabetes by the public and private sectors is needed to limit the severe toll that diabetes exacts in the U.S.