The role of Statins and the NLRP3 Inflammasome in Type 2 Diabetes

Statins reduce cholesterol and have been very successful in the management of cardiovascular disease
(CVD). Several studies have evidenced that satins also exhibit direct anti-inflammatory effects, independent
of their LDL-lowering properties.Statins recently however have been implicated in the risk of developing
Type 2 Diabetes Melitus (T2DM) and appear to exert pro-inflammatory as well as anti-inflammatory
effects, dependent on statin type and dose. There is a clinical need therefore, for the development of a
new test to determine the correct statin prescription for patients with and at risk of CVD and T2DM.

The NLRP3 inflammasome pathway has been identified as a mechanism responsible for the effect of
statins on immune function. A recent study demonstrated that atorovastin but not rosuvastin decreased
the NLRP3 inflammsome in patients with coronary artery disease. However, a series of findings
demonstrated that some statins exert the opposite effect leading to increased NLRP3 inflammasome
activation leading to impaired insulin signalling in a mouse model of T2DM. This project will investigate the
mechanisms of action of statins on glycaemic control. The project will also investigate if NLRP3 and its
associated regulatory proteins may be a novel biomarker panel for patient stratification of statins.
This project will be in collaboration with a multidisciplinary team of support including academics, clinicians
and statisticians. The successful applicant will gain training in a broad range of techniques pertinent to the
exciting and emerging area of precision medicine at the new Northern Ireland Centre for Stratified
Medicine.