Associations between adipocytokines and severity of cardiovascular autonomic neuropathy in well-controlled type 2 diabetes and prediabetes

Abstract

Background It is thought that adipocytokines contribute to autonomic dysfunction and cardiovascular risks in type 1 and type 2 diabetes mellitus (T1DM and T2DM, respectively). We aimed to identify adipocytokines that are associated with the severity of cardiovascular autonomic neuropathy (CAN) in patients with well-controlled T2DM and prediabetes. Methods The complete cardiovascular autonomic function and biomarkers were assessed for each patient. The severity of CAN was assessed using both the composite autonomic scoring scale (CASS) and the cardiac autonomic reflex tests (CARTs) score. Biomarkers included adipocytokines (leptin, chemerin, adiponectin, and vaspin), oxidative stress (thiols and thiobarbituric acid-reactive substance [TBARS]), endothelial dysfunction (sICAM-1 and sVCAM-1), and insulin resistance (triglyceride/high-density lipoprotein cholesterol [HDL-C] ratio and homeostasis model assessment of insulin resistance [HOMA-IR] index). Results A total of 107 patients were included in this study: 90 with diabetes and 17 with prediabetes. Stepwise logistic regression showed that diabetes duration and leptin level were independently associated with the presence of CAN. Leptin level was positively correlated with body mass index (r = 0.588, P < 0.0001), waist circumference (r = 0.504, P < 0.0001), urinary albumin-to-creatinine ratio (r = 0.351, P = 0.001), hs-CRP (r = 0.291, P = 0.006), TBARS (r = 0.259, P = 0.008), triglyceride/HDL-C ratio (r = 0.346, P < 0.0001), and HOMA-IR index (r = 0.304, P = 0.008) but negatively correlated with thiols (r=-0.25, P = 0.011) level. The leptin level was strongly associated with the CASS (r = 0.36, P < 0.0001) and CARTs (r = 0.356, P < 0.0001) scores. Stepwise linear regression analysis also showed that the leptin level was significantly associated with the CASS and CARTs scores, respectively. Conclusions As the leptin level is considered a prognostic factor in CAN, a longitudinal study is needed to confirm the association between a decrease in obesity and reduced leptin levels and CAN progression.