Drug Classes For Prevention Research Articles

Repurposing anti-inflammasome NRTIs for improving insulin sensitivity and reducing type 2 diabetes development

Innate immune signaling through the NLRP3 inflammasome is activated by multiple diabetes-related stressors, but whether targeting the inflammasome is beneficial for diabetes is still unclear. Nucleoside reverse-transcriptase inhibitors (NRTI), drugs approved to treat HIV-1 and hepatitis B infections, also block inflammasome activation. Here, we show, by analyzing five health insurance databases, that the adjusted risk of incident diabetes is 33% lower in patients with NRTI exposure among 128,861 patients with HIV-1 or hepatitis B (adjusted hazard ratio for NRTI exposure, 0.673; 95% confidence interval, 0.638 to 0.710; P < 0.0001; 95% prediction interval, 0.618 to 0.734). Meanwhile, an NRTI, lamivudine, improves insulin sensitivity and reduces inflammasome activation in diabetic and insulin resistance-induced human cells, as well as in mice fed with high-fat chow; mechanistically, inflammasome-activating short interspersed nuclear element (SINE) transcripts are elevated, whereas SINE-catabolizing DICER1 is reduced, in diabetic cells and mice. These data suggest the possibility of repurposing an approved class of drugs for prevention of diabetes.

Bone health issues in women with early-stage breast cancer receiving aromatase inhibitors

Bone health is an important issue for women with all stages of breast cancer, but especially those with early-stage breast cancer receiving aromatase inhibitors (AIs). AIs have been shown to reduce bone mineral density and are associated with an increased incidence of fractures. Although AIs significantly improve survival times in early-stage breast cancer patients, many of these patients eventually develop metastatic bone disease. Therefore, identifying effective strategies for preventing bone metastases is needed. Results of preclinical studies with bisphosphonates show increased tumor cell kill in several breast cancer cell lines, but study results evaluating this class of drugs for prevention of bone metastases in women with early-stage breast cancer receiving adjuvant therapies have been inconsistent. However, several large studies to clarify the role of bisphosphonates in maintaining or improving bone health in these women are under way.