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Background  The new HbA1c criteria for diagnosis of pre-diabetes have been criticised for misdiagnosis. It is possible that some elevation of HbA1c is not driven by hyperglycaemia. This study assesses associations of HbA1c, commonly assumed to relate solely to glucose concentration, with (i) smoking, a major source of reactive oxygen species (ROS) and (ii) fruit & vegetables consumption associated with improved redox status.    Methods  One-way ANOVA, Chi-squared and multivariate linear regressions, adjusted for all known confounders were used to explore associations of HbA1c with self-reported smoking status and fruit & vegetables consumptions in the Scottish Health Surveys 2003–2010, among individuals without known diabetes and HbA1c < 6.5%.    Results  Compared to non-smokers (n = 2831), smokers (n = 1457) were younger, consumed less fruit & vegetables, had lower physical activity levels, lower BMI, higher HbA1c and CRP (p < 0.05). HbA1c was higher in smokers by 0.25 SDs (0.08%), and 0.38 SDs higher (0.14%) in heavy smokers (>20 cigarettes/day) than non-smokers (p < 0.001 both). Smokers were twice as likely to have HbA1c in the 'pre-diabetic’ range (5.7-6.4%) (p < 0.001, adj.model). Pre-diabetes and low grade inflammation did not affect the associations. For every extra 80 g vegetable portion consumed, HbA1c was 0.03 SDs (0.01%) lower (p = 0.02), but fruit consumption did not impact on HbA1c, within the low range of consumptions in this population.    Conclusion  This study adds evidence to relate smoking (an oxidative stress proxy) with protein glycation in normoglycaemic subjects, with implications for individuals exposed to ROS and for epidemiological interpretation of HbA1c.

Influence of smoking and diet on glycated haemoglobin and 'pre-diabetes’ categorisation: a cross-sectional analysis