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Elevated A1c in Adults without a History of Diabetes in the U.S.

Posted: Wednesday, June 10, 2009

A single elevated A1C level (A1C >6%) is common in the general population of adults without a history of diabetes and is highly reliable for the detection of elevated fasting glucose. And 77% of individuals with A1C ≥6.5% had FPG ≥126 mg/dl which is the definition for the diagnosis of diabetes.

The objective of the present study was to examine the prevalence and correlates of elevated A1C in a large, nationally representative sample of U.S. adults without diagnosed diabetes who participated in the National Health and Nutrition Examination Survey (NHANES) (1999–2006). We hypothesized that 1) elevated A1C levels (e.g., A1C >6%) are common in the general population of nondiabetic adults in the U.S. and 2) A1C levels would be associated with risk factors for Type 2 diabetes and its complications even in the absence of elevated glucose levels.

This analysis suggests that elevated A1C (>6%) is common in the general population of nondiabetic adults. The overall prevalence of A1C >6% was 3.8%, corresponding to 7.1 million individuals in the U.S. population. Approximately 45% of these individuals have IFG and 45% have fasting glucose ≥126 mg/dl. Elevated A1C levels were particularly common among older adults, non-Hispanic blacks, and obese individuals. We found that demographic characteristics and risk factors for Type 2 diabetes and its complications including older age, male sex, nonwhite race/ethnicity, lower attained education level, adiposity, and hypercholesterolemia were associated with elevated A1C even in the presence of normal fasting glucose.

Significant advantages of adopting A1C for the screening and diagnosis of diabetes are the high repeatability of the measurement and the high specificity of elevated values for detecting undiagnosed diabetes. Recent recommendations have stated that diagnosis based on A1C should be confirmed using a glucose-dependent test (FPG or OGTT) or by a second A1C. However, glucose-dependent tests are less reliable (repeatable) than A1C. Requiring confirmation of a highly reliable test by one that is less reliable poses problems for the interpretation of any discrepancy between the two values.

In a previous study, repeated measurements were analyzed which were taken 2 weeks apart on an unselected sample of individuals without diabetes and found that 100% of individuals with A1C ≥7% had a second A1C measurement of ≥7% 2 weeks later and 80% of individuals with A1C ≥6.5 had an A1C level ≥6.5% 2 weeks later. There is little marginal gain to repeating the A1C test within a short (several week) time period. Furthermore, we show in the present study that 92% of individuals with A1C ≥7.0% also had FPG ≥126 mg/dl and 77% of individuals with A1C ≥6.5% had FPG ≥126 mg/dl. At the population level, elevated A1C is rare in the absence of elevated fasting glucose. Additional advantages to using A1C for screening and/or diagnosis of diabetes include national standardization of the assay, the low analytic variability (high methodological quality of the assay, even when compared with glucose), the widespread availability of the A1C test and its current use in the management and treatment of diabetes, and the fact that the patient does not need to fast.

It is unclear why nondiabetic non-Hispanic blacks have consistently higher A1C values even in the setting of normal fasting glucose levels and after adjustment for demographic and clinical characteristics. Further research should be conducted to determine whether this disparity stems from racial differences in postprandial glycemia or from racial differences in the tendency of hemoglobin to undergo glycosylation.

This study has several strengths including the large, nationally representative sample of healthy, nondiabetic individuals.

To date, the diagnostic utility of A1C has largely been assessed by its accuracy (as measured by its sensitivity and specificity) to detect glucose-defined cases of diabetes. The concordance of A1C with fasting glucose is important and, as confirmed by our data, an A1C ≥6.5% is specific for the detection of undiagnosed diabetes defined by a single fasting glucose level. Thus, it seems reasonable to adopt a single elevated A1C value as being diagnostic for diabetes. However, the real test of utility for A1C as a screening or diagnostic test of diabetes is its association with long-term clinical outcomes in an initially nondiabetic population specifically in comparison with fasting glucose levels. To address this question we need large, observational studies of A1C in populations of individuals without diabetes. The purpose of the study was to examine the prevalence and correlates of elevated A1C in a large, nationally representative sample of adults without diabetes in the U.S.

A1C is an integrated measure of circulating glucose levels and tracks well in individuals over time. Epidemiological studies have shown that A1C values in nondiabetic adults predict incident diabetes, cardiovascular disease morbidity and mortality, and total mortality. In these studies, A1C values well within the “normal” range (i.e., A1C <6%) were independently associated with clinical outcomes. There is currently renewed interest in using A1C for diagnosis and/or screening for diabetes; however, there have been few epidemiological investigations of A1C in nondiabetic adults.

Source: Diabetes In Control: Diabetes Care May 2009 vol. 32 no. 5 828-833

 
 
 
 
 
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