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World J Diabetes. Oct 15, 2016; 7(18): 433-440
Published online Oct 15, 2016. doi: 10.4239/wjd.v7.i18.433
Nitrate-nitrite-nitrosamines exposure and the risk of type 1 diabetes: A review of current data
Zahra Bahadoran, Asghar Ghasemi, Parvin Mirmiran, Fereidoun Azizi, Farzad Hadaegh
Zahra Bahadoran, Parvin Mirmiran, Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran 19395-4763, Iran
Asghar Ghasemi, Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran 19395-4763, Iran
Fereidoun Azizi, Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran 19395-4763, Iran
Farzad Hadaegh, Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran 19395-4763, Iran
Author contributions: Bahadoran Z, Ghasemi A and Hadaegh F prepared the manuscript; Bahadoran Z, Mirmiran P and Hadaegh F designed and implemented the study; Mirmiran P, Azizi F and Hadaegh F revised and supervised overall project; all authors read and approved the final version of manuscript.
Conflict-of-interest statement: The authors declare no conflicts of interest regarding this manuscript.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Parvin Mirmiran, PhD, Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, No. 24, Sahid-Erabi St, Yemen St, Chamran Exp, Tehran 19395-4763, Iran. mirmiran@endocrine.ac.ir
Telephone: +98-21-22432500 Fax: +98-21-22416264
Received: April 7, 2016
Peer-review started: April 8, 2016
First decision: June 12, 2016
Revised: June 30, 2016
Accepted: August 15, 2016
Article in press: August 16, 2016
Published online: October 15, 2016
Abstract

The potential toxic effects of nitrate-nitrite-nitrosamine on pancreatic β cell have remained a controversial issue over the past two decades. In this study, we reviewed epidemiological studies investigated the associations between nitrate-nitrite-nitrosamines exposure, from both diet and drinking water to ascertain whether these compounds may contribute to development of type 1 diabetes. To identify relevant studies, a systematic search strategy of PubMed, Scopus, and Science Direct was conducted using queries including the key words “nitrate”, “nitrite”, “nitrosamine” with “type 1 diabetes” or “insulin dependent diabetes mellitus”. All searches were limited to studies published in English. Ecologic surveys, case-control and cohort studies have indicated conflicting results in relation to nitrate-nitrite exposure from drinking water and the risk of type 1 diabetes. A null, sometimes even negative association has been mainly reported in regions with a mean nitrate levels < 25 mg/L in drinking water, while increased risk of type 1 diabetes was observed in those with a maximum nitrate levels > 40-80 mg/L. Limited data are available regarding the potential diabetogenic effect of nitrite from drinking water, although there is evidence indicating dietary nitrite could be a risk factor for development of type 1 diabetes, an effect however that seems to be significant in a higher range of acceptable limit for nitrate/nitrite. Current data regarding dietary exposure of nitrosamine and development of type 1 diabetes is also inconsistent. Considering to an increasing trend of type 1 diabetes mellitus (T1DM) along with an elevated nitrate-nitrite exposure, additional research is critical to clarify potential harmful effects of nitrate-nitrite-nitrosamine exposure on β-cell autoimmunity and the risk of T1DM.

Keywords: Nitrate, Nitrite, Nitrosamine, Type 1 diabetes

Core tip: The potential toxic effects of nitrate-nitrite-nitrosamine on pancreatic β cell have remained a controversial issue over the past two decades. Ecologic surveys, case-control and cohort studies have indicated conflicting results in relation to nitrate-nitrite exposure from drinking water and the risk of type 1 diabetes. An increased risk of type 1 diabetes was observed in regions with a maximum nitrate levels > 40-80 mg/L. Dietary nitrite could be a risk for development of type 1 diabetes in a higher range of acceptable limit. Additional research is critical to clarify potential harmful effects of nitrate-nitrite-nitrosamine exposure on β-cell autoimmunity and the risk of type 1 diabetes mellitus.