Sustained epigenetic reprogramming of innate immune cells in response to pathogens, termed ’trained immunity’ or ’innate immune memory’, beneficially converts cellular functionality to protect from secondary infections. However, inappropriate activation of immunological imprinting mediated by ’trained immunity’ may contribute to reinforced immune responses in inflammatory diseases, such as Type 2 Diabetes mellitus (T2DM), obesity and cardiovascular diseases.
We have previously shown that a hyperlipidemic environment is capable of inducing trained innate immunity and that the immune system misinterprets Western-type diets as a pathogenic threat. Yet, how a sustained Western diet or hyperglycemic-induced innate immune cell reprogramming is reflected in human remains to be elusive.
The FAIR study is designed to prospectively investigate in T2DM patients whether
i. Hyperglycemia alters innate immune cell responsiveness
ii. ...whether this is accompanied by a changed immune cell gene signature
iii. ...whether a potential epigenetic imprinting can be reversed by T2DM remission through formula diet controlled weight management
The public health benefit of this clinical intervention study is in deciphering novel dietary metabolites/ biomarkers being crucially involved in altered innate immune cell responsiveness. The outcomes of this study may provide new therapeutic targets to reduce the development of T2DM linked to excess CVD risk.
European Foundation for the Study of Diabetes/ Boehringer Ingelheim