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In 2014, the National Health Insurance Service (NHIS) signed a memorandum of understanding with the Korean Diabetes Association to provide limited open access to its databases for investigating the past and current status of diabetes and its management. NHIS databases include the entire Korean population; therefore, it can be used as a population-based nationwide study for various diseases, including diabetes and its complications. This report presents how we established the analytic system of nation-wide population-based studies using the NHIS database as follows: the selection of database study population and its distribution and operational definition of diabetes and patients of currently ongoing collaboration projects.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce cardiovascular events in humans with type 2 diabetes (T2D); however, the underlying mechanism remains unclear. Activation of the NLR family, pyrin domain-containing 3 (NLRP3) inflammasome and subsequent interleukin (IL)-1β release induces atherosclerosis and heart failure. Here we show the effect of SGLT2 inhibitor empagliflozin on NLRP3 inflammasome activity. Patients with T2D and high cardiovascular risk receive SGLT2 inhibitor or sulfonylurea for 30 days, with NLRP3 inflammasome activation analyzed in macrophages. While the SGLT2 inhibitor's glucoselowering capacity is similar to sulfonylurea, it shows a greater reduction in IL-1β secretion compared to sulfonylurea accompanied by increased serum β-hydroxybutyrate (BHB) and decreased serum insulin. Ex vivo experiments with macrophages verify the inhibitory effects of high BHB and low insulin levels on NLRP3 inflammasome activation. In conclusion, SGLT2 inhibitor attenuates NLRP3 inflammasome activation, which might help to explain its cardioprotective effects.