Association of Urinary Nitrate With Diabetes Complication and Disease-Specific Mortality Among Adults With Hyperglycemia

Abstract Context The hyperglycemia condition disrupts metabolism of nitrate/nitrite and nitric oxide, and dietary nitrate intake can restore nitric oxide homeostasis. Objective This study aims to examine whether urinary nitrate is associated with diabetes complications and long-term survival among people with hyperglycemia. Methods A total of 6208 people with hyperglycemia who participated in the National Health and Nutrition Examination Survey from 2005 to 2014 were enrolled. Diabetes complications included congestive heart failure, coronary heart disease, angina, stroke, myocardial infarction, diabetic retinopathy, and nephropathy. Mortality was obtained from the National Death Index until 2015. Urinary nitrate was measured by ion chromatography coupled with electrospray tandem mass spectrometry, which was log-transformed and categorized into tertiles. Logistic regression models and Cox proportional hazards models were respectively performed to assess the association of urinary nitrate with the risk of diabetes complications and disease-specific mortalities. Results After adjustment for potential confounders, including urinary perchlorate and thiocyanate, compared with the participants in the lowest tertile of nitrate, the participants in the highest tertile had lower risks of congestive heart failure (odds ratio [OR] 0.41; 95% CI, 0.27-0.60) and diabetic nephropathy (OR 0.50; 95% CI, 0.41-0.62). Meanwhile, during a total follow-up period of 41 463 person-years, the participants in the highest tertile had lower mortality risk of all-cause (hazard ratio [HR] 0.78; 95% CI, 0.62-0.97), cardiovascular disease (CVD) (HR 0.56; 95% CI, 0.37-0.84), and diabetes (HR 0.47; 95% CI, 0.24-0.90), which showed dose-dependent linear relationships (P for nonlinearity > 0.05). Moreover, no association between nitrate and cancer mortality was observed (HR 1.13; 95% CI, 0.71-1.80). Conclusion Higher urinary nitrate is associated with lower risk of congestive heart failure and diabetic nephropathy, and lower risk of all-cause, CVD, and diabetes mortalities. These findings indicate that inorganic nitrate supplementation can be considered as a supplementary treatment for people with hyperglycemia.