Fibrinogen Function Indexs, Potential Biomarkers, are Closely Connected to Diabetic Peripheral Neuropathy

Abstract Background and Objectives: Research suggested that diabetic peripheral neuropathy (DPN) was related to plasma fibrinogen (Fib) concentration, while there was no research on the correlation with fibrinogen function. In this study, two indexes reflecting the function of plasma fibrinogen, k value and angle α, were used to analyze its correlation with DPN, and to explore the possibility of using them as biological indicators for diagnosing DPN.Subjects and methods: This study is a prospective observational clinical study. About 561 T2DM patients were enrolled and divided into the diabetes with symptomatic neuropathy group (161 cases), the diabetes with asymptomatic neuropathy group (132 cases) and the diabetes with no neuropathy group (268 cases). Meanwhile, 160 healthy unrelated subjects were recruited as control group. The levels of k value and angle α were detected.Results: The Fib levels increased slightly in diabetic subjects with neuropathy compared with those without. The angle α levels increased slightly in diabetic with asymptomatic neuropathy subjects compared with diabetes with no neuropathy subjects, and the levels increased greatly in diabetic subjects with symptomatic neuropathy compared with those without. The k value levels declined slightly in diabetic with asymptomatic neuropathy subjects compared with diabetes with no neuropathy subjects, and the levels declined greatly in diabetic subjects with symptomatic neuropathy compared with those without. The association of k value and angle α with diabetic neuropathy was independent of the hyperglycemic state (HbA1c, duration) and other potential confounders affecting k value and angle α levels (e.g., age, Fib, vitamin B12 and renal status) (odds ratio 0.080 [0.051–0.124], P= 0.001; odds ratio 1.131 [1.063–1.204], P= 0.001). In addition, k value and angle α levels were closely correlated to the stages of neuropathy (r= -0.686, P = 0.000; r= 0.314, P = 0.000). Meanwhile, the optimal cutoff point for k value levels to distinguish patients with diabetic neuropathy from those without was 1.8min, with a sensitivity of 73.7% and a specificity of 83.2% (AUC= 0.873). The optimal cutoff point for angle α levels was 60deg, with a sensitivity of 41.0% and a specificity of 95.6% (AUC= 0.669).Conclusions: The levels of k value and angle α are closely associated with peripheral neuropathy in patients with diabetes. The levels of k value and angle α may be helpful for early diagnosis of diabetic peripheral neuropathy.