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Aim: To evaluate the U.S. population-level impact of two alternatives for initial type 2 diabetes screening [opportunistic random plasma glucose (RPG) > 6.7 mmol/l and a 1-h 50-g glucose challenge test (GCT) > 8.9 mmol/l] compared with American Diabetes Association (ADA)-recommended tests., Methods: Using a sample (n = 1471) from the National Health and Nutrition Examination Survey (NHANES) 2013-2014 that represented 145 million U.S. adults at high risk for developing type 2 diabetes, we simulated a two-test screening process. We compared ADA-recommended screening tests [fasting plasma glucose (FPG), 2-h 75-g oral glucose tolerance test (OGTT), HbA 1c ] vs. initial screening with opportunistic RPG or GCT (followed by FPG, OGTT or HbA 1c ). After simulation, participants were entered into an individual-level Monte Carlo-based Markov lifetime outcomes model. Primary outcomes were representative number of U.S. adults correctly identified with type 2 diabetes, societal lifetime costs and quality-adjusted life years (QALYs)., Results: In NHANES 2013-2014, 100 individuals had undiagnosed diabetes [weighted estimate: 8.4 million, standard error (se): 1.1 million]. Among ADA-recommended screening tests, FPG followed by OGTT (FPG-OGTT) was most sensitive, identifying 35 individuals with undiagnosed diabetes (weighted estimate: 3.2 million, se: 0.9 million). Four alternative screening strategies performed superior to FPG-OGTT, with RPG followed by OGTT being the most sensitive overall, identifying 72 individuals with undiagnosed diabetes (weighted estimate: 6.1 million, se: 1.0 million). There was no increase in average lifetime costs and comparable QALYs., Conclusions: Initial screening using opportunistic RPG or a GCT may identify more U.S. adults with type 2 diabetes without increasing societal costs., (© 2020 Diabetes UK.)

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.)

Aims: To determine whether HbA 1c mismatches (HbA 1c 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 HbA 1c 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 HbA 1c was determined from the linear regression modelling the relationship between observed HbA 1c 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 HbA 1c ], 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 HbA 1c 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 HbA 1c 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 HbA 1c in diagnostic classification should be performed in most individuals., (Published 2019. This article is a U.S. Government work and is in the public domain in the USA.)

Aim: To characterize differences between black and white people in optimal HbA 1c 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 HbA 1c 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 HbA 1c was evaluated for a range of HbA 1c 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 HbA 1c 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 HbA 1c thresholds in black people than in white people suggest a need to individualize HbA 1c relative to glucose levels if HbA 1c is used to diagnose diabetes and prediabetes., (© 2019 Diabetes UK.)

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 HbA 1c 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/m 2 , 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 HbA 1c 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., (© 2016 Diabetes UK.)

Aim: To determine whether using HbA1c for screening and management could be confounded by age differences, whether age effects can be explained by unrecognized diabetes and prediabetes, insulin resistance or postprandial hyperglycaemia, and whether the effects of aging have an impact on diagnostic accuracy., Methods: We conducted a cross-sectional analysis in adults without known diabetes in the Screening for Impaired Glucose Tolerance (SIGT) study 2005-2008 (n=1573) and the National Health and Nutrition Examination Survey (NHANES) 2005-2006 (n=1184)., Results: Both glucose intolerance and HbA(1c) levels increased with age. In univariate analyses including all subjects, HbA(1c) levels increased by 0.93 mmol/mol (0.085%) per 10 years of age in the SIGT study and by 1.03 mmol/mol (0.094%) per 10 years in the NHANES; in both datasets, the HbA(1c) increase was 0.87 mmol/mol (0.08%) per 10 years in subjects without diabetes, and 0.76 mmol/mol (0.07%) per 10 years in subjects with normal glucose tolerance, all P<0.001. In multivariate analyses of subjects with normal glucose tolerance, the relationship between age and HbA(1c) remained significant (P<0.001) after adjustment for covariates including race, BMI, waist circumference, sagittal abdominal diameter, triglyceride/HDL ratio, and fasting and 2-h plasma glucose and other glucose levels, as assessed by an oral glucose tolerance test. In both datasets, the HbA(1c) of an 80-year-old individual with normal glucose tolerance would be 3.82 mmol/mol (0.35%) greater than that of a 30-year-old with normal glucose tolerance, a difference that is clinically significant. Moreover, the specificity of HbA(1c) -based diagnostic criteria for prediabetes decreased substantially with increasing age (P<0.0001)., Conclusions: In two large datasets, using different methods to measure HbA(1c), the association of age with higher HbA(1c) levels: was consistent and similar; was both statistically and clinically significant; was unexplained by features of aging; and reduced diagnostic specificity. Age should be taken into consideration when using HbA(1c) for the diagnosis and management of diabetes and prediabetes., (Published 2014. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

Aims: To understand the metabolic and temporal links in the relationship between diabetes and depression, we determined the association between depressive symptoms and unrecognized glucose intolerance., Methods: In a cross-sectional study, 1047 subjects without known diabetes were screened for diabetes or pre-diabetes using the oral glucose tolerance test and for depressive symptoms using the Patient Health Questionnaire (PHQ)., Results: Mean age was 48 years, body mass index 30 kg/m(2); 63% were female, 54% black, 11% previously treated for depression and 10% currently treated; 5% had diabetes and 34% pre-diabetes. Median PHQ score was 2 (interquartile range 0-5). Depressive symptoms did not increase with worsening glucose tolerance, after adjusting for age, sex, ethnicity, body mass index, family history, exercise, education and depression treatment., Conclusions: There is no association between depressive symptoms and unrecognized glucose intolerance. However, it remains possible that diagnosed diabetes, with its attendant health concerns, management issues, and/or biological changes, may be a risk for subsequent development of depression. Thus, patients with newly diagnosed diabetes should be counselled appropriately and monitored for the development of depression.

Aims: Ageing increases the likelihood of developing diabetes, with associated cardiovascular disease. In a cross-sectional study, we sought to determine whether age is associated with an increase in glucose concentrations 1 h after an oral glucose challenge (1-h OGTT), even when glucose tolerance is normal (NGT)., Methods: Among subjects in the NHANES II database, 2591 subjects with NGT and documented 1-h OGTT glucose concentrations were studied. The relationship between age and 1-h OGTT glucose concentrations was assessed in a multivariable linear regression analysis., Results: In a multivariable linear regression analysis, each 10-year increase in age conferred an additional 0.20 mmol/l increase in the 1-h OGTT glucose (P < 0.0001). Moreover, an interaction between age and gender was found such that 1-h OGTT glucose concentrations rose more rapidly with increasing age in men than in women. The impact of age on 1-h OGTT glucose was independent of both fasting and 2-h OGTT glucose concentrations., Conclusions: One-hour OGTT glucose concentrations rise significantly with age even in subjects with NGT. Further investigation is warranted to explore the pathophysiological significance of such age-related impairment of glucose handling, which might increase the risk of cardiovascular disease even when patients do not meet criteria for the diagnosis of diabetes or prediabetes.