Retinopathy develops at similar glucose levels but higher HbA1c levels in people with black African ancestry compared to white European ancestry: evidence for the need to individualize HbA1c interpretation.

AIMS: To examine the association of HbA1c 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 HbA1c , 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/m2 , HbA1c 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). HbA1c 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 HbA1c , 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 HbA1c 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 HbA1c levels in black people for a given level of average plasma glucose, strategies may be needed to individualize the interpretation of HbA1c measurements.

Impact of mismatches in HbA1c vs glucose values on the diagnostic classification of diabetes and prediabetes.

AIMS: To determine whether HbA1c mismatches (HbA1c levels that are higher or lower than expected for the average glucose levels in different individuals) could lead to errors if diagnostic classification is based only on HbA1c levels. METHODS: In a cross-sectional study, 3106 participants without known diabetes underwent a 75-g oral glucose tolerance test (fasting glucose and 2-h glucose) and a 50-g glucose challenge test (1-h glucose) on separate days. They were classified by oral glucose tolerance test results as having: normal glucose metabolism; prediabetes; or diabetes. Predicted HbA1c was determined from the linear regression modelling the relationship between observed HbA1c and average glucose (mean of fasting glucose and 2-h glucose from the oral glucose tolerance test, and 1-h glucose from the glucose challenge test) within oral glucose tolerance test groups. The haemoglobin glycation index was calculated as [observed - predicted HbA1c ], and divided into low, intermediate and high haemoglobin glycation index mismatch tertiles. RESULTS: Those participants with higher mismatches were more likely to be black, to be men, to be older, and to have higher BMI (all P<0.001). Using oral glucose tolerance test criteria, the distribution of normal glucose metabolism, prediabetes and diabetes was similar across mismatch tertiles; however, using HbA1c criteria, the participants with low mismatches were classified as 97% normal glucose metabolism, 3% prediabetes and 0% diabetes, i.e. mostly normal, while those with high mismatches were classified as 13% normal glucose metabolism, 77% prediabetes and 10% diabetes, i.e. mostly abnormal (P<0.001). CONCLUSIONS: Measuring only HbA1c could lead to under-diagnosis in people with low mismatches and over-diagnosis in those with high mismatches. Additional oral glucose tolerance tests and/or fasting glucose testing to complement HbA1c in diagnostic classification should be performed in most individuals.

Racial differences in performance of HbA1c for the classification of diabetes and prediabetes among US adults of non-Hispanic black and white race.

AIM: To characterize differences between black and white people in optimal HbA1c thresholds for diagnoses of diabetes and prediabetes. METHODS: Data were included from the National Health and Nutrition Examination Survey, 2005-2014. Black and white adults (age 18-70 years) who underwent an oral glucose tolerance test and had available fasting plasma glucose, 2-h plasma glucose and HbA1c measurements were eligible for inclusion. Diabetes or prediabetes status was defined by fasting plasma glucose and 2-h plasma glucose using American Diabetes Association criteria. Classification of diabetes, prediabetes and dysglycaemia by HbA1c was evaluated for a range of HbA1c thresholds, with optimal thresholds defined as those values that maximized the sum of sensitivity and specificity (Youden's index). RESULTS: In 5324 black (32.3%) and white (67.7%) individuals, Youden's index (optimal) thresholds for HbA1c were ≥42 mmol/mol (6.0%) and ≥39 mmol/mol (5.7%) for discriminating diabetes vs non-diabetes, ≥ 44 mmol/mol (6.2%) and ≥39 mmol/mol (5.7%) for discriminating diabetes vs prediabetes (excluding normoglycaemia), ≥39 mmol/mol (5.7%) and ≥37 mmol/mol (5.5%) for discriminating dysglycaemia vs normoglycaemia, and ≥39 mmol/mol (5.7%) and ≥37 mmol/mol (5.5%) for discriminating prediabetes vs normoglycaemia (excluding diabetes), in black and white people, respectively. CONCLUSIONS: Consistently higher optimal HbA1c thresholds in black people than in white people suggest a need to individualize HbA1c relative to glucose levels if HbA1c is used to diagnose diabetes and prediabetes.

Glucose challenge test screening for prediabetes and early diabetes.

AIMS: To test the hypothesis that a 50-g oral glucose challenge test with 1-h glucose measurement would have superior performance compared with other opportunistic screening methods. METHODS: In this prospective study in a Veterans Health Administration primary care clinic, the following test performances, measured by area under receiver-operating characteristic curves, were compared: 50-g oral glucose challenge test; random glucose; and HbA1c level, using a 75-g oral glucose tolerance test as the 'gold standard'. RESULTS: The study population was comprised of 1535 people (mean age 56 years, BMI 30.3 kg/m2 , 94% men, 74% black). By oral glucose tolerance test criteria, diabetes was present in 10% and high-risk prediabetes was present in 22% of participants. The plasma glucose challenge test provided area under receiver-operating characteristic curves of 0.85 (95% CI 0.78-0.91) to detect diabetes and 0.76 (95% CI 0.72-0.80) to detect high-risk dysglycaemia (diabetes or high-risk prediabetes), while area under receiver-operating characteristic curves for the capillary glucose challenge test were 0.82 (95% CI 0.75-0.89) and 0.73 (95% CI 0.69-0.77) for diabetes and high-risk dysglycaemia, respectively. Random glucose performed less well [plasma: 0.76 (95% CI 0.69-0.82) and 0.66 (95% CI 0.62-0.71), respectively; capillary: 0.72 (95% CI 0.65-0.80) and 0.64 (95% CI 0.59-0.68), respectively], and HbA1c performed even less well [0.67 (95% CI 0.57-0.76) and 0.63 (95% CI 0.58-0.68), respectively]. The cost of identifying one case of high-risk dysglycaemia with a plasma glucose challenge test would be $42 from a Veterans Health Administration perspective, and $55 from a US Medicare perspective. CONCLUSIONS: Glucose challenge test screening, followed, if abnormal, by an oral glucose tolerance test, would be convenient and more accurate than other opportunistic tests. Use of glucose challenge test screening could improve management by permitting earlier therapy.