Leptin mediate central obesity on the severity of cardiovascular autonomic neuropathy in well-controlled type 2 diabetes and prediabetes

Abstract

Background: Evidences support the view that central obesity is an independently cardiovascular risk. It is thought that leptin contributes to autonomic dysfunction and cardiovascular risks in type 1 and type 2 diabetes mellitus (T1DM and T2DM). This raises the possibility that leptin might mediate the relationship between central obesity and the severity of cardiovascular autonomic neuropathy (CAN) in patients with well-controlled T2DM and prediabetes. Methods: The complete cardiovascular reflex tests and biomarkers were assessed for each patient. The severity of CAN was assessed using composite autonomic scoring scale (CASS). A single-level three-variable mediation model was used to investigate the possible relationships among central obesity [as indicated by waist circumference (WC)], leptin level, and severity of CAN (as indicated by CASS value). Results: A total of 107 patients were included in this study: 90 with diabetes and 17 with prediabetes. The results demonstrate that increased WC is associated with increased severity of CAN (r = 0.242, P = 0.017). We further discovered that leptin level is positively correlated with WC (r = 0.504, P < 0.0001) and the CASS value (r = 0.36, P < 0.0001). Further mediation analysis shows that leptin level serves as mediators between higher WC and higher CASS. Conclusions: Our results highlighted the relationship among leptin, central obesity, and severity of CAN. As the leptin level serves as mediator between central obesity and severity of CAN, a longitudinal study is needed to confirm that control of WC can decrease leptin levels and can be effective in reducing CAN progression.