Abstract
BACKGROUND: Antidiabetic treatment is linked with an increased risk of hypoglycemia. Several clinical studies have demonstrated that hypoglycemia exposure elevates the risk of cardiovascular diseases in diabetic patients. Our previous research has shown that non-severe recurrent hypoglycemia (RH) exposure increases the risk of thrombosis in young insulin-treated diabetic (ITD) rats. Given that a substantial subset of diabetes patients who experience cardiovascular complications are elderly and the effect of non-severe RH on thrombosis risk in aged subjects remains unknown, we tested the hypothesis that prior RH exposure enhances thrombosis in aged ITD rats. METHODS: Aged, insulin-treated streptozotocin-diabetic Wistar rats of both sexes were randomly assigned to either the recurrent hyperinsulinemic euglycemia control or the recurrent hyperinsulinemic hypoglycemia group. The risk of thrombosis was quantified using an in vivo model. RESULTS: RH increases the risk of thrombosis in male ITD rats 7 days after exposure. A twice-weekly hypoglycemia exposure for 6 weeks also elevated the risk of thrombosis in male rats. Similar exposures to RH also increased the risk of thrombosis in aged female rats. CONCLUSIONS: Exposure to non-severe RH increases the risk of thrombosis in aged ITD rats of both sexes. Nonetheless, it remains uncertain whether aging influences the characteristics of thrombosis observed in RH-exposed young ITD rats as well as its clinical consequences, highlighting the need for further research.