Aumento das concentrações plasmáticas de leucotrieno B4 em indivíduos com diabetes mellitus tipo 2 e neuropatia autonômica cardiovascular

Abstract

Diabetes Mellitus (DM) is a complex chronic disease associated with high morbidity and mortality due to its chronic complications, which involve, among other things, low-grade chronic inflammation. Among the chronic complications, cardiovascular autonomic neuropathy (NAC) is characterized by impairment of the cardiovascular autonomic control secondary to damage to the autonomic fibers responsible for the innervation of the heart and blood vessels. This complication increases the incidence of unfavorable cardiovascular outcomes. Due to the importance of the autonomic nervous system in the modulation of inflammation (the inflammatory reflex is a physiological mechanism by which the vagus nerve regulates the immune function and inhibits the excessive production of pro-inflammatory cytokines) and given the participation of inflammation in the development of diabetes chronic complications, the present project had the primary objective of evaluating whether plasma concentrations of tumor necrosis factor (TNF), interleukin (IL) 10 (IL10), IL1 and leukotriene B4 (LTB4) differed between individuals with Type 2 diabetes (T2D) with different degrees of NAC. The secondary objective was to correlate the concentrations of these pro-inflammatory markers with the degree of glycemic control and insulin resistance. A total of 129 individuals (62% women with a median age [interquartile range] of 63 [59-67] years with a disease duration of 8 [4-15] years and HbA1c of 7.3 [6.3-9.1]%) were selected and divided into three groups: 44 without NAC, 41 with incipient NAC (two groups considered without definitive NAC) and 44 individuals with definitive NAC. Demographic, clinical, and biochemical data were collected, and blood samples were taken to measure TNF, IL10, IL1 and LTB4 by enzyme immunoassay. The Lipid accumulation product (LAP) was calculated as a surrogate marker of insulin resistance. The diagnosis of CAN was performed by the Ewing Tests combined with the spectral analysis of Heart Rate Variability (HRV). There was an increase in plasma concentrations of TNF and LTB4 in the group of individuals with definitive NAC compared to those without definitive NAC, while the anti-inflammatory cytokine IL10 was lower in the group of individuals with definitive NAC. These differences lost statistical significance for TNF and IL10 after adjusting for other variables, but not for LTB4 (mean ± standard deviation: 63.1 ± 16.4 versus 71.5 ± 15.7; P = 0.016; without definitive NAC versus with definitive NAC, respectively). Plasmatic concentrations of LTB4 presented a weak borderline correlation with LAP only in women. In conclusion, LTB4 plasmatic concentrations were significantly higher in individuals with T2D with definitive NAC compared to those without definitive NAC.