The role of fibrinolysis in the development of prediabetes-associated coronary heart disease: a focus on the plasminogen activator inhibitor -1 and its potential use as a predictive marker in diet-induced prediabetes.

Introduction: Type 2 diabetes mellitus (T2DM) is associated with an increased risk of cardiovascular diseases (CVD). However, the onset of T2DM is preceded by prediabetes, which is associated with sedentary lifestyles and consumption of high-calorie diets. Studies have shown that impaired glucose homeostasis creates an environment for developing T2DM-related complications. Using a high-fat-high-carbohydrate diet-induced prediabetes animal model, this study sought to assess the risk factors of coronary heart disease (CHD) in diet-induced prediabetes and identify biomarkers that can be used for early detection of prediabetes-associated CHD. Methods: Male Sprague Dawley rats were randomly grouped into two groups and were kept on different diets for 20 weeks ( Results: There was significant insulin resistance accompanied by significantly increased HbA1c and body weight in PD compared to NPD. Simultaneously, there was a significant increase in inflammatory cytokines in PD compared to NPD. This was accompanied by significantly increased TG and VLDL and endothelial dysfunction in PD. The association between HOMA-IR and PAI-1 was insignificantly positive in NPD, whereas a significantly strong positive association was observed in PD. Conclusion: There is a positive correlation between insulin resistance and PAI-1 during prediabetes; therefore, suggesting that prediabetes increases the risk of developing vascular thrombosis. The current therefore study warrants further investigation on PAI-1 and other markers of fibrinolysis for the early detection of thrombosis and risk of CHD in prediabetes.