Abstract
OBJECTIVES: This cohort study investigated the possible association of dietary nitrate (NO(3))/nitrite (NO(2)) intake and risk of progression to type 2 diabetes (T2D) across different phenotypes of prediabetes (Pre-DM). METHODS: A total of 1586 adults diagnosed with Pre-DM [i.e., 60.2% isolated impaired fasting glucose (iIFG), 21% isolated impaired glucose tolerance (iIGT), and 18.8% combined IFG-IGT] in the third (2006-2008) and fourth (2009-2011) examinations of the Tehran Lipid and Glucose Study, were assessed for dietary intake of NO(3) and NO(2) and were followed up to 2015-2017. Cox proportional hazard models, stratified by Pre-DM phenotypes, were used to plot cumulative hazard curve and calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for developing T2D across tertile categories and per every 100 mg/d NO(3) and 2 mg/d NO(2) intake exceeded the acceptable daily intake (ADI). RESULTS: The mean age of the participants was 47.2 ± 12.9 years at baseline, and 52.2% were men. Highest intake of NO(3) (≥ 645 vs. < 451 mg/d) and NO(2) (≥ 11.5 vs. <9.0 mg/d) increased risk of T2D among subjects with iIFG (HR = 1.69, 95% CI = 1.04-2.74 and HR = 2.07, 95% CI = 1.29-3.32). The cumulative hazards were higher in the highest compared to the lowest NO(3) and NO(2) intake in subjects with iIFG phenotype. Every 100 mg/d of NO(3) and 2 mg/d NO(2) intake exceeded ADI was associated with an increased risk of progression from iIFG to T2D by 13 and 25%, respectively. CONCLUSION: High exposure to dietary NO(3) and NO(2) may be a risk factor for developing T2D in subjects with iIFG.