Abstract
The contribution of cows’ milk containing beta-casein protein A1 variant to the development of type 1 diabetes (T1D) has been controversial for decades. Despite epidemiological data demonstrating a relationship between A1 beta-casein consumption and T1D incidence, direct evidence is limited. We demonstrate that early life exposure to A1 beta-casein through the diet can modify progression to diabetes in non-obese diabetic (NOD) mice, with the effect apparent in later generations. Adult NOD mice from the F0 generation and all subsequent generations (F1 to F4) were fed either A1 or A2 beta-casein supplemented diets. Diabetes incidence in F0–F2 generations was similar in both cohorts of mice. However, diabetes incidence doubled in the F3 generation NOD mice fed an A1 beta-casein supplemented diet. In F4 NOD mice, subclinical insulitis and altered glucose handling was evident as early as 10 weeks of age in A1 fed mice only. A significant decrease in the proportion of non-conventional regulatory T cell subset defined as CD4+CD25−FoxP3+ was evident in the F4 generation of A1 fed mice. This feeding intervention study demonstrates that dietary A1 beta-casein may affect glucose homeostasis and T1D progression, although this effect takes generations to manifest.
Highlights
Type 1 diabetes (T1D) results from the autoimmune destruction of insulin-producing beta cells in the pancreatic islets of Langerhans [1,2,3], culminating in the loss of blood-glucose homeostasis.type 1 diabetes (T1D) poses a serious health problem: the inability to regulate blood glucose levels necessitates exogenous insulin for survival; suboptimal glycemic control may lead to long-term complications resulting in substantial disability and reduced lifespan [4]
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Summary
Type 1 diabetes (T1D) results from the autoimmune destruction of insulin-producing beta cells in the pancreatic islets of Langerhans [1,2,3], culminating in the loss of blood-glucose homeostasis. T1D poses a serious health problem: the inability to regulate blood glucose levels necessitates exogenous insulin for survival; suboptimal glycemic control may lead to long-term complications resulting in substantial disability and reduced lifespan [4]. Federation estimated that there were 437,500 children that have diabetes worldwide in 2007. Of all individuals with T1D, 70,000 young children under the age of 14 years, developing per year and the incidence will rise by 3% globally [5,6]. T1D is a global disease, there is geographical variation with respect to incidence and prevalence [7]. The cause of geographical variation could be due to differences in genetic and environmental risk factors [8]
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