Neuropatia autonômica cardiovascular precoce em pacientes com lipodistrofia generalizada congênita

Abstract

The metabolic abnormalities of congenital generalized lipodystrophy (LGC) can present with severe dyslipidemia, diabetes mellitus (DM) difficult to control and microvascular complications, among which diabetic neuropathy. Nevertheless, the evaluation of different forms of neuropathy, including the study of cardiovascular autonomic modulation in these patients is limited. It is believed that hyperglycemia alone can not explain all the pathophysiology of nerve injury and among the factors potentially involved the development stand to insulin resistance (IR) and abnormal lipid metabolism. It also observes association between cardiovascular autonomic neuropathy (CAN), inflammation, kidney disease and left ventricular hypertrophy (LVH). These observations make LGC an interesting biological model to study the mechanisms likely associated with these complications. The objectives of this study were to determine the prevalence of NAC through the evaluation tests of heart rate variability (HRV) and to analyze the association between clinical and metabolic markers, autonomic tests and cardiovascular parameters in patients with LGC. This was cross-sectional study conducted in the pediatric endocrinology clinic of the University Hospital Walter Cantídio, from October 2013 to December 2015. We included 10 patients with LGC, 20 individuals with DM1 and 20 healthy participants who underwent assessment clinical, laboratory exams and imaging, molecular analysis, measurement of mass index of VE (LVMI), QTc and thickness mean carotid intima (CEMI). For diagnosis of NAC were performed cardiovascular autonomic reflex tests - Valsalva coefficients (VAL), respiratory (E / I), orthostatic (30/15) and test of postural hypotension (THP) - and the spectral analysis of HRV - components very low frequency (VLF), low (FB) and high (AF). The clinical diagnosis of NAC was defined by the presence of at least two abnormal reflex tests. The results were expressed as median (min; max) and absolute and percentage frequency. We used Fisher's exact test, Mann-Whitney, Spearman correlation and resampling technique Bootstrap, Program: stata 13. Significant p <0.05. In the LGC group, six (60%) were female, age was 12 years (7; 30), 1 (10%) pre-pubescent, 7 (70%) pubescent and two 2 adults. There was no difference in age, sex, pubertal stage, and BMI between groups. All patients had LGC dyslipidemia, DM 70%, 60% and 30% nephropathy sensorimotor neuropathy. A higher prevalence of clinical NAC in patients with LGC (40%) compared to DM1 group (5%) and healthy (0%); p <0.05. A significant reduction in the ratio E / I and FMB components FB and FA in the LGC group vs DM1 and healthy and lower values ​​of 30/15 and VAL coefficients in the LGC group vs healthy (p <0.05). Patients with LGC showed a high prevalence of LVH (40% vs. 0%; p = 0.008). In patients with LGC, cardiovascular autonomic tests were associated with HbA1c, HOMA-IR, triglycerides, CRP, albuminuria, LVMI and interventricular septum thickness (p <0.05). When evaluating the LGC and healthy groups, leptin levels associated with the 30/15 coefficient even after adjustment for triglycerides and insulin resistance (r = 0.396; p = 0.036). In conclusion, it was demonstrated a high prevalence of NAC in young patients with LGC, even compared to a group of DM1. These findings suggest that IR and hypertriglyceridemia may be involved in the early development of NAC. It was also observed association between leptin and cardiovascular autonomic modulation; it is noteworthy, however, that further studies are needed to evaluate the role of hipoleptinemia this context. The association between LVH and parameters of evaluation of cardiac autonomic modulation allows speculate that NAC may be involved in the pathogenesis of this complication in these patients.