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, 2h 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). ResultsIn 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.
Objectives This study examined the influence of diet on the methylome by analyzing 428,019 cytosine-guanine nucleotide pair (CpG) sites and assessing whether diet quality was associated with differential methylation patterns. Methods The study population included 4529 women from the Women's Health Initiative (WHI) observation and clinical trial from three ancillary studies: EMPC, BAA23, and AS311. DNA methylation was measured from whole blood samples using the Illumina Infinium HumanMethylation450 Beadchip. Diet quality was assessed using the Alternative Healthy Eating Index 2010 (AHEI-2010). An epigenome-wide association study (EWAS) meta-analysis, stratified by study cohort, was done using generalized linear models by regressing methylation β values (β = Methylated probes/[Methylated + Unmethylated probes]) for each CpG site on the primary exposure, AHEI, adjusting for cell composition, chip number and location, study characteristics, principle components of genetic relatedness, age, ethnicity and BMI. Significance was set at Holm-Bonferroni P < 0.05. Results Demographic characteristics are described by quartile of AHEI with Quartile 4 equivalent to the healthiest diet (highest score) and Quartile 1 equivalent to the poorest diet (lowest score) in Table 1. We found diet quality was significantly associated with 340 CpG sites after false discovery correction (Figure 1). While statistically significant, effect sizes were small (∼0.0003). These findings suggest that, on average, as AHEI increases by one SD (10.1 units), methylation changes by only ±0.003 in associated CpG sites. When examining the top 20 CpG sites (Table 2), several sites were located in genes critical to metabolism, including cg26137868 in the FOXA2 gene and cg20006924 in the RORA gene, both related to the regulation of glucose and fat metabolism and 3 CpG sites in the SLC18A2, SLC2A14, and SLC16A3 genes related to nutrient transport. Conclusions This is the first reported EWAS examining the relationship between diet quality and methylation in humans. While diet quality was statistically associated with many CpG sites, the effect sizes were small. Further investigation is required to understand the relationship between diet quality and the methylome. Funding Sources NA. Supporting Tables, Images and/or Graphs
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