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Effect of Aging on A1C Levels in Individuals Without Diabetes

Evidence from the Framingham Offspring Study and the National Health and Nutrition Examination Survey 2001–2004

¹ Diabetes Center and Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
² Department of Health and Mental Hygiene, New York, New York
³ National Heart, Lung, and Blood Institute Framingham Heart Study, Framingham, Massachusetts
⁴ Department of Endocrinology, Metabolism, and Hypertension, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
⁵ Department of Biostatistics, Boston University, Boston, Massachusetts

Corresponding author: Lydie Pani, lpani{at}partners.org

OBJECTIVE—Although glycemic levels are known to rise with normal aging, the nondiabetic A1C range is not age specific. We examined whether A1C was associated with age in nondiabetic subjects and in subjects with normal glucose tolerance (NGT) in two population-based cohorts.

RESEARCH DESIGN AND METHODS—We performed cross-sectional analyses of A1C across age categories in 2,473 nondiabetic participants of the Framingham Offspring Study (FOS) and in 3,270 nondiabetic participants from the National Health and Nutrition Examination Survey (NHANES) 2001–2004. In FOS, we examined A1C by age in a subset with NGT, i.e., after excluding those with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT). Multivariate analyses were performed, adjusting for sex, BMI, fasting glucose, and 2-h postload glucose values.

RESULTS—In the FOS and NHANES cohorts, A1C levels were positively associated with age in nondiabetic subjects. Linear regression revealed 0.014- and 0.010-unit increases in A1C per year in the nondiabetic FOS and NHANES populations, respectively. The 97.5th percentiles for A1C were 6.0% and 5.6% for nondiabetic individuals aged <40 years in FOS and NHANES, respectively, compared with 6.6% and 6.2% for individuals aged 70 years (P_trend < 0.001). The association of A1C with age was similar when restricted to the subset of FOS subjects with NGT and after adjustments for sex, BMI, fasting glucose, and 2-h postload glucose values.

CONCLUSIONS—A1C levels are positively associated with age in nondiabetic populations even after exclusion of subjects with IFG and/or IGT. Further studies are needed to determine whether age-specific diagnostic and treatment criteria would be appropriate.

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