The association between hypoglycemia and panvascular disease in type 2 diabetes patients: The correlation structure mediated by inflammatory and metabolic abnormalities

BackgroundHypoglycemia in type 2 diabetes patients is associated with metabolic abnormalities and inflammation that affect vascular beds. The relationship between hypoglycemia and panvascular disease (PVD) is not clear. This study aimed to investigate the association between PVD and hypoglycemia, and to identify potential mediators.MethodThis retrospective cross-sectional study enrolled Patients from two centers in Chongqing China, and the results were further validated using UK Biobank data. Logistic regression was used to test the association of hypoglycemia and PVD. Stratification and interaction analyses to test the effects across study subgroups. Forward (hypoglycemia to PVD) and reverse (PVD to hypoglycemia) relationships were analyzed by structural equation modeling (SEM), which included interleukin-6, neutrophil-to-lymphocyte ratio, uric acid, hemoglobin A1c, and systolic blood pressure.Results22,128 patients diagnosed with T2DM at two large centers and 44442 T2DM participants from the UK Biobank were enrolled. A significant association between hypoglycemia and PVD was found. Subgroup analysis found hypoglycemia was more strongly associated with PVD in patients with inflammatory abnormalities and metabolic dysfunction. SEM suggested a correlation structure between hypoglycemia and PVD which might mutually aggravated each other through inflammation and metabolism pathways.ConclusionThis is the first study that described the correlation structure between hypoglycemia and PVD with a large population. Within this potential mutual association, inflammation and metabolism might be mediators. Our study also highlights the insufficient attention clinicians pay to hypoglycemia and PVD, and further attention is needed in future clinical practice and research.