Endocrine Abstracts

Statins are among the most widely prescribed medications worldwide, decreasing the risk of cardiovascular diseases by reducing cholesterol levels. However, statins also increase the risk of incident type 2 diabetes (T2D), disproportionately affecting women compared to men. Inflammation has emerged as a central factor underpinning T2D pathology, with macrophages playing a significant role. Statins have been found to influence macrophage inflammatory responses, and this has been linked to statin-induced insulin resistance in murine adipose tissue. However, whether sex differences exist in statin-mediated macrophage inflammatory responses and the potential underlying mechanism(s) that drive differential responses has yet to be defined. Treatment of bone-marrow derived macrophages from wild-type c57bl/6 male and female mice with 10 μM simvastatin for 24h decreased Il10 mRNA expression in both male (0.22-fold, P=0.0002, n=3) and female BMDMs (0.13-fold, P<0.0001, n=3) whilst increasing Il1b mRNA levels (10.45-fold in males and 4.83-fold in females, n=4). These findings demonstrate that statins stimulate a pro-inflammatory response in both male and female macrophages, which may contribute to the diabetogenic action of statins. Ongoing analysis will reveal further statin-mediated macrophage responses, the impact of sex and how these factors may contribute to women’s increased statin-induced diabetes risk.