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Aims: To assess the prevalence and clinical implications of "mismatches" between HbA1c and glucose levels in the United States across the life course., Methods: Participants ages 12-79 years from U.S. National Health and Nutrition Examination Survey (NHANES) 2005-2016 without known diagnosis of diabetes and who had a 75 g oral glucose tolerance test were included. Previously undiagnosed diabetes (DM), prediabetes, and normal glucose metabolism (NGM) were defined using American Diabetes Association cut-points. Mismatches were defined by the hemoglobin glycation index (HGI)., Results: In 10,361 participants, 5% and 41% had diabetes and prediabetes, respectively, by fasting or 2-hour glucose criteria. By HbA1c criteria, the high HGI tertile consisted of mostly abnormal classification (3% DM, 52% prediabetes) and the low HGI tertile contained mostly normal classification (78% NGM). Across all ages, 15% (weighted: 30 million individuals) had clinically significant mismatches of HGI magnitude ≥+0.5% (i.e., high mismatch) or ≤-0.5% (low mismatch). Mismatch was most common in older adults and non-Hispanic Black participants., Conclusions: Mismatches of clinically significant magnitude could lead to HbA1c-related misdiagnosis or inappropriate management in up to 30 million Americans. Older adults, non-Hispanic Black individuals, and others with high mismatches may benefit from complementing HbA1c with additional diagnostic and management strategies., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Aims: To examine the association of HbA 1c and glucose levels with incident diabetic retinopathy according to black African or white European ancestry., Methods: In this retrospective cohort study of 202 500 US Veterans with diabetes (2000-2014), measures included HbA 1c , outpatient random serum/plasma glucose, and incident retinopathy [conversion from negative to ≥2 positive evaluations (ICD-9 codes), without a subsequent negative]., Results: At baseline, the study population had a mean age of 59.3 years, their mean BMI was 31.9 kg/m 2 , HbA 1c level was 57 mmol/mol (7.4%) and glucose level was 8.8 mmol/l, and 77% were of white European ancestry (white individuals) and 21% of black African ancestry (black individuals). HbA 1c was 0.3% higher in black vs white individuals (P < 0.001), adjusting for baseline age, sex, BMI, estimated glomerular filtration rate (eGFR), haemoglobin, and average systolic blood pressure and glucose. Over 11 years, incident retinopathy occurred in 9% of black and 7% of white individuals, but black individuals had higher HbA 1c , glucose, and systolic blood pressure (all P < 0.001); adjusted for these factors, incident retinopathy was reduced in black vs white individuals (P < 0.001). The population incidence of retinopathy (7%) was associated with higher mean baseline HbA 1c in individuals with black vs white ancestry [63 mmol/mol (7.9%) vs 58 mmol/mol (7.5%); P < 0.001)], but with similar baseline glucose levels (9.0 vs 9.0 mmol/l; P = 0.660, all adjusted for baseline age, sex and BMI)., Conclusions: Since retinopathy occurs at higher HbA 1c levels in black people for a given level of average plasma glucose, strategies may be needed to individualize the interpretation of HbA 1c measurements., (© 2020 Diabetes UK.)