Environmental/lifestyle factors in the pathogenesis and prevention of type 2 diabetes

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• Indeed, within 1 week there is partial recovery of insulin production after the introduction of a very low calorie diet, with further normalisation in the following months [155, 184]. Recovery of β-cell function to varying extents is also seen early after gastric bypass

• Prebiotic plant fibres promote growth of a diverse and apparently healthy microbiota with less endotoxin leakage

• This may avoid inflammatory activation of endothelial and Kupffer cells in the liver with concomitant hepatocyte dysfunction, as usually observed in response to a western-type high-fat diet or during non-alcoholic fatty liver disease

• A fibre-rich diet gives rise to the enhanced production of short-chain fatty acids by gut bacteria

• There is direct binding of these products to the free fatty acid receptor 2 on β-cells and the promotion of cell growth and function

• A second major diabetes-protective component of plant food are phytochemicals. A property common to most phytochemicals is the activation of cell defence and anti-inflammatory genes, for instance, via the Nrf2 signalling pathway [169]. These effects occur body-wide and are also demonstrable in β-cells

• A third major diabetes-protective factor is exercise. Interestingly, muscle work also activates cell defence and anti-inflammatory pathways via Nrf2 signalling. There is a direct beneficial effect of exercise on β-cell function [171], and also on liver function in non-alcoholic fatty liver disease, although there is no body weight loss

• The lower level of protein synthesis decreases the demand of ATP from mitochondria, thereby reducing the amount of concomitantly released radical oxygen species and allowing recovery of mitochondrial proteins from oxidative damage such as nitrosylation or carbonylation