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

Author:

Jiang Wenbo12ORCID,Zhang Jia1,Yang Ruiming1,Sun Xinyi1,Wu Huanyu1,Zhang Jiacheng1,Liu Siyao3,Sun Changhao1,Ma Lifang4,Han Tianshu1,Wei Wei15

Affiliation:

1. Department of Nutrition and Food Hygiene, The National Key Discipline, School of Public Health, Harbin Medical University , Harbin 150081 , P. R. China

2. Department of Cardiology, The First Affiliated Hospital of Harbin Medical University , Harbin 150081 , China

3. Division of Epidemiology, Biostatistics and Environmental Health, School of Public Health, University of Memphis , Memphis, TN 38152 , USA

4. Department of Pharmacology, College of Pharmacy Key Laboratory of Cardiovascular Research, Ministry of Education, Harbin Medical University , Harbin 150081 , P. R. China

5. Department of Geriatrics, The First Affiliated Hospital of Harbin Medical University , Harbin 150001 , P. R. China

Abstract

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.

Funder

HMU Marshal Initiative Funding

China Postdoctoral Science Foundation Funded Project

Heilongjiang Province Postdoctoral Science Foundation Funded Project

Publisher

The Endocrine Society

Subject

Biochemistry (medical),Clinical Biochemistry,Endocrinology,Biochemistry,Endocrinology, Diabetes and Metabolism

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