HbA1c levels are widely used for diabetes diagnosis and management but may misrepresent underlying glucose levels. To assess potential misdiagnoses of diabetes (T2DM) and prediabetes (PreDM) by HbA1c, we examined representative samples of non-pregnant adults and youth in the National Health and Nutrition Examination Survey (NHANES), 2005-2016, who had a 75g OGTT. Normal glucose metabolism (NGM), PreDM, and T2DM were defined by ADA criteria. For each glycemic group, a linear regression model of HbA1c vs. glucose (i.e., mean of FPG and 2hrPG) yielded predicted HbA1c for each participant. The Hemoglobin Glycation Index (HGI), defined as observed - predicted HbA1c, was partitioned into tertiles. Of 10,737 adults aged 18-79 year (representing N=199,270,935), 52% female and 10% non-Hispanic black, with mean age 43.7 year and BMI 28.5 kg/m2. By OGTT criteria, 81.2% had NGM, 14.1% PreDM, and 4.6% T2DM. The high HGI tertile had a higher proportion of non-Hispanic black race (17.7%, vs. middle 8.7%, low 7.0%), as well as higher mean BMI and age, all p<0.0001. A higher proportion of black race in the high HGI tertile was also found in adults >65 year (p=0.0016, weighted N=24,142,366) and youth aged 12-17 year (p<0.0001, n=2,218, weighted N=25,302,585). Across HGI tertiles, the distribution among diagnostic categories was similar by OGTT criteria, but differed by HbA1c criteria; those in the high HGI tertile were 53.7% PreDM and 3.5% T2DM - mostly abnormal, while those in the low HGI tertile were 98.0% NGM and 1.0% PreDM - mostly normal, with a similar pattern in older adults and youth, all p<0.0001. Across all age groups, 15% (weighted N=33,569,933) had clinically significant HGI deviations of >0.5%.
Conclusion: Diagnostic classification by HbA1c alone could lead to misdiagnosis in over 33 million Americans, a problem across all age groups. Overdiagnosis is a particular risk in those with black race, higher BMI, and older age. Complementing HbA1c with glucose testing should improve diagnostic classification and management.
L.R. Staimez: None. L. Kipling: None. C.N. Ford: None. J. Ham: None. M.K. Rhee: None. L.S. Phillips: Advisory Panel; Self; Janssen Pharmaceuticals, Inc. Research Support; Self; AbbVie Inc., GlaxoSmithKline plc., Kowa Pharmaceutical Europe Co. Ltd., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Pfizer Inc. Stock/Shareholder; Self; Diasyst Inc. Other Relationship; Self; Diasyst Inc., Janssen Pharmaceuticals, Inc.