Insulin resistance is now implicated in the development of a number of Western lifestyle diseases including type 2 diabetes, obesity and cardiovascular disease. In addition, deleterious changes to the brain, that can result in dementia may also be caused by the development of insulin resistance. The aetiology of insulin resistance is not fully understood, but one hypothesis that is supported by a large amount of evidence suggests that the cellular changes that lead to a decrease in insulin sensitivity are caused by oxidative stress. Diets that increase the degree of oxidative stress in the body through the generation of free radicals may therefore increase the risk of developing insulin resistance. Low quality diets are implicated in the generation of free radicals because not only are they low in antioxidants they are also high in chemicals and food components that can generate free radicals in tissues. Of these sodium nitrite and sodium nitrate, preservative often used in cured and processed meats, have been particularly well studied.
Sodium nitrite and sodium nitrate are detrimental because they undergo chemical changes in the stomach that leads to the formation of nitrosamines. Nitrosamines form through chemical reaction between nitrites and proteins, and nitrates can be converted to nitrites in the low pH of the stomach. Nitrosamines can cause DNA damage through alkylation of guanine, and in addition they are able to cause the generation of reactive oxygen species (ROS, a subgroup of oxygen containing free radicals) including the superoxide radical and hydrogen peroxide. These ROS then interact with tissues where they cause lipid peroxidation and protein dysfunction. Interaction with the membranes of cells may cause changes to the structures required for the function of the insulin receptor and its associated second messenger system, ultimately leading to insulin resistance. Animal experiments have been used to provide evidence that nitrosamines are carcinogenic, and this evidence has been extensively studies.
However, that nitrosamines can cause insulin resistance is less well studied. That being said, a small number of animal studies do show detrimental effects for nitrosamines on the function of the insulin system. For example, in one study1, rats were injected with N-nitrosodiethylamine (NDEA) for 2 to 4 weeks and then a number of biochemical tests were performed. The results of the study showed that NDEA treatment lead to the development of type 2 diabetes, nonalcoholic steatohepatitis (NASH), poor motor function, impaired spatial learning and neurodegeneration characterised by insulin resistance. The rats also experienced a significant increase in lipid peroxidation and cellular changes to brain tissue similar to that observed in Alzheimer’s disease. Pro-inflammatory cytokines also increased significantly in the rats. Exposure to nitrosamine compounds therefore play a pivotal role in the development of insulin resistance and its associated conditions in rats, and may play a similar role in humans.
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