In a representative sample of the U.S. adult population, the prevalence of those at high risk of diabetes varied greatly by the indicator used to measure risk. For example, the prevalence of prediabetes as measured by IFG100 (26.2%) was almost twice that measured by A1C5.7 (14.2%) and IGT (13.7%) and over three times that of IFG110 (7.0%). The combination of either A1C5.7 or IFG100 resulted in a prevalence of almost 33%. Thus, if these indicators are used to identify the number of individuals eligible for prevention efforts, the number of individuals would range from 15.3 million (7% with IFG110) to 70.9 million (32.2% with A1C5.7-IFG100). If all three measures are combined, the number of individuals at high risk of diabetes would be 80.8 million (36.7% with A1C5.7, IFG100 or IGT).
Our study suggests that the specific choice of a prediabetes measure will yield differing associations with age, sex, and race. Although the prevalence of A1C5.7 and IGT was similar for men and women, IFG100 or IFG110 was about 1.7 times higher among men than women. These sex differences in prevalence are consistent with the findings of several international studies. Summarizing data from 13 European and 10 Asian studies, the writing committee for the International Diabetes Federation IGT/IFG consensus statement (14
) found IFG110 to be consistently more common in men than women, typically 1.5–3 times higher. Although the reasons for this sex differential are unknown, some have suggested that the underlying etiologies or metabolic determinants of FPG and OGTT values may differ (14
). Further, analysis of the Diabetes Prevention Program data suggested that progression to diabetes was more dependent upon FPG in men, whereas progression in women was more dependent on OGTT (16
). Regardless of the reasons for the sex differences in IFG prevalence, epidemiological research and prevention programs solely using IFG to determine prediabetes status will identify a preponderance of men. For every 100 people eligible for enrollment in prevention programs based on IFG, about 63 would be men and 37 would be women.
In our study, prediabetes prevalence measured by A1C5.7 was about two times higher in non-Hispanic blacks than in non-Hispanic whites and Mexican Americans, but was only half that of non-Hispanic whites and Mexican Americans when measured by IGT or IFG110. Prior research comparing A1C and FPG and/or OGTT prediabetes definitions noted ethnic differences in prevalence and suggested changes to diagnostic criteria of diabetes or prediabetes may lead to substantial changes in prevalence among different ethnic groups (14
). Some warned that using A1C alone to screen for type-2 diabetes risks misdiagnosing large numbers of patients, especially those of African, Mediterranean, or south-east Asian heritage (23
) and/or may be particularly insensitive in diagnosing whites (19
). Further, studies have raised the concern that the relationship between A1C and other glycemic markers differs by race and ethnicity (21
). For example, compared with their Caucasian counterparts, African Americans in particular have higher A1C levels at any given level of FPG. This may be influenced in part by genetic traits influencing erythrocyte turnover, or alternatively, by nutritional or metabolic factors. Whether this variation in the relationship among different glycemic markers affects prediction of morbid outcomes or whether the benefit that can be expected from interventions is strong enough to warrant ethnic-specific disease thresholds is not yet clear. However, a recent analysis of prospective cohort data from the Atherosclerosis Risk in Communities study did not support the use of race-specific cut points in A1C for identifying individuals at risk for diabetes (5
In NHANES, limited data were available for some race/ethnic groups at high risk for diabetes, such as Native Americans. However, the major strengths of this study are the nationally representative data and the inclusion of standardized laboratory, clinical, and physical measurements.
Our findings confirm prior observations that considerable discordance between A1C, IFG, and IGT exists, and that the characteristics of individuals identified at risk for diabetes vary by risk indicator. This has implications for prevention programs concerning who will be identified and enrolled in prevention efforts. A1C5.7 may disproportionately identify non-Hispanic blacks, while IFG may disproportionately identify men. Due to the lack of a gold standard for comparison, it is unknown whether these measures are biased or whether these groups are actually at a higher or lower risk of developing type 2 diabetes. The use of a combination of either A1C5.7or IFG100 approximately equalizes prevalence by race/ethnicity, somewhat lessens sex differences, and identifies the majority with IGT (upon whom the prevention trials were based). However, using this combination identifies nearly a third of the U.S. population as at risk for developing diabetes. Because within each risk indicator the risk of diabetes increases across a continuum (6
), it could be argued that intervention resources should be targeted toward those at greatest risk. Programs to prevent diabetes may need to consider issues of equity, resources, need, and efficiency in targeting their efforts.