Leukotriene Pathway Activation Associates with Poor Glycemic Control and with Cardiovascular Autonomic Neuropathy in Type 1 Diabetes

Abstract

Background and Aims. Since hyperglycemia promotes inflammation by different pathways and inflammation participates in the development of chronic diabetes complications, we investigated the association between the leukotriene (LT) pathway and microvascular diabetes complications.Methods and Results. Quantitative polymerase chain reaction was employed to quantify the expression ofALOX5(encodes 5-lipoxygenase),LTB4R(encodes one of the LTB4 receptors), andMYD88in peripheral blood mononuclear cells from 164 type 1 diabetes (T1D) individuals presenting or not diabetes kidney disease, retinopathy, peripheral neuropathy, and cardiovascular autonomic neuropathy (CAN); 26 nondiabetic subjects were included as controls. LTB4 plasmatic concentrations were also evaluated. The expression ofLTB4Rwas significantly higher in T1D individuals than in controls. T1D individuals with microvascular complications presented lowerMYD88mRNA expression when compared to those without microvascular complications. Higher LTB4 concentrations were found in individuals with CAN versus without CAN. The observation of two distinct subgroups of T1D individuals in the correlation analyses motivated us to evaluate the characteristics of each one of these groups separately. The group presenting higher expression ofALOX5and ofLTB4Ralso presented higher values of HbA1C, of fructosamine, and of plasmatic LTB4.Conclusion. In the diabetes setting, the LT pathway is not only activated by hyperglycemia but is also modulated by the status of the autonomic nervous system.