Abstract
BACKGROUND: A decade ago, systemic inflammation became widely recognized as an etiology of type 2 diabetes mellitus (T2DM) and complications thereof. Senescent CD8 + T cells of T2DM patients exhibit increased secretion of pro-inflammatory cytokines and enhanced expression of cytotoxic molecules, contributing to systemic inflammation. Recently, many anti-inflammatory roles played by statins and ezetimibe (cholesterol-lowering drugs) have been reported. We will explore the effects of statin/ezetimibe therapy on CD8 + T cell senescence in patients with T2DM and hypercholesterolemia. METHODS: This 2-group, parallel, randomized, controlled clinical trial will recruit 108 subjects with T2DM and low-density lipoprotein-cholesterol (LDL-C) levels ≥100 mg/dL and randomly assign them to rosuvastatin/ezetimibe and rosuvastatin groups at a 1:1 ratio. Blood samples will be drawn at baseline and after 12 weeks of medication. The primary outcomes will be the LDL-C-lowering effects after 12 weeks. The secondary outcomes will be changes in the senescent (CD28 - CD57+) CD8 + T cell proportions; the levels of circulating pro-inflammatory cytokines, cytotoxic molecules, interleukin-1, transforming growth factor-β, fasting glucose, and HbA1c; and biochemical indices of kidney, liver, and muscle function. Symptoms and signs of predictable adverse events (myopathy and hepatitis) will be routinely monitored. DISCUSSION: We will evaluate the effects of statin/ezetimibe on CD8 + T cell senescence. Statin/ezetimibe may exert a beneficial immunomodulatory effect.