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Metabolic / inflammatory markers and simpathovagal balance in patients with metabolic syndrome and obstructive sleep apnea: effect of hypocaloric diet and physical training

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Author(s):
Felipe Xerez Cepêda Fonseca
Total Authors: 1
Document type: Doctoral Thesis
Press: São Paulo.
Institution: Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD)
Defense date:
Examining board members:
Ivani Credidio Trombetta; Fernanda de Cordoba Lanza; Fabiano Pinheiro da Silva
Advisor: Ivani Credidio Trombetta
Abstract

Background. The frequent association between metabolic syndrome (MetS) and obstructive sleep apnea (OSA) impairs the sympathovagal balance, which mechanisms are not fully known. Metabolic and inflammatory alterations could be explain, at least in part, this autonomic dysfunction. Hypocaloric diet and exercise training (D+ET) the first choice therapy in the treatment of SMet and may impact the improvement of these parameters. Objectives. Verify whether the overlap of OSA and MetS has an additive effect on metabolic and inflammatory markers and if these alterations are associated with sympathovagal unbalance. Additionally, to investigate the effect of D+ET over MetS risk factors, OSA severity, heart rate recovery after maximal exercise, the sympathovagal balance and metabolic and inflammatory markers. Methods. We studied 67 patients newly diagnosed with MetS (ATP-III), non-diabetic, without medication. A healthy control group (CS, n=19) was also recruited for the study. OSA was defined by the apnea-hypopnea index (AHI) >15 events/hour (polysomnography, PSG). The groups MetS with OSA (MetS+OSA, n=36) and without OSA (MetS-OSA, n=31) were divided in two groups. The intervention by D+ET (D was decrease of 500 kcal/day, and ET, 50-70% of peakVO2, 3x/week, 1h) or control group (C, follow up without intervention): MetS+OSA/D+ET (n=19), MetS+OSA/C (n=10), MetS-OSA/D+ET (n=14) and MetS + OSA/C (n=13). The pre and post period of 4 months of D+ET or C, were measured: PSG; microneurography (muscular sympathetic nerve activity, MSNA); cardiopulmonary exercise test (CPET) for evaluated the oxygen uptake (peakVO2) and heart rate (HR) response; glucose and insulin (HOMA-IR, QUICKI); oral glucose tolerance test for evaluate the area under the curve (AUCglucose and AUCinsulin); leptin; adiponectin; TNF-alpha; PCR; IL1-beta; IL-6. In addition, HR variability (LF=low frequency, HF=high frequency, LF/HF=sympathovagal balance). Results. In pre-intervention, except for fasting glucose, both MetS groups were similar and different from CS group in the weight, MetS risk factors and LF and HF/LF. MetS+OSA and MetS-OSA showed impairment in ANSM and HF compared to CS. In addition, MetS+OSA impairment in ANSM and HF compared to MetS-OSA. Compared to CS, only the MetS+OSA showed differences in fasting glucose (P < 0.001), leptin (P=0.03), glucose ASC (P=0.001), insulin ASC (P=0.02), HOMA-IR (P < 0.001), QUICKI (P < 0.001), TNF-alpha (P < 0.05). In addition, glycemia ASC (P = 0.004) and QUICKI (P = 0.04) were worse in MetS+OSA than to MetS-OSA. The ANSM correlated with leptin (R=0.27, P=0.03), ASC (R=0.38, P=0.002), ASC insulin; (R=0.26; P=0.04) and QUICK (R=-0.30; P=0.02). After intervention by D+TF, the MetS+OSA and MetS-OSA groups showed a reduction in the ANSM and improvement in the recovery of the HR after the TECP.Only the MetS+OSA group submitted to D+ET showed a diminished in AHI (37±3.5 vs. 23±3.4 events/h, P=0.003), fasting insulin (13±1.3 vs. 9±1, P=0.02), HOMA-IR (3.4±0.4 vs. 2.2±0.3 ?UI/mL, P=0.03) and QUICKI (0.32±0.01 vs. 0.35±0.01, P=0.04). The C groups did not change for intervention. Conclusion. In patients with non-diabetic MetS, the OSA leads to an inflammatory state and impairs in metabolic and autonomic control. The OSA also carries a sympathetic exacerbation that can be explained in part by the metabolic glucose, insulin, and leptin impairment. In patients with OSA, D+ET decreased the AHI and insulin resistance. Independently of AOS, D+ET decreased SMet number and improved autonomic control (AU)

FAPESP's process: 15/03274-0 - Diet and exercise improves metabolic, inflammatory changes and sympathovagal balance in patients with metabolic syndrome and obstructive sleep apnea
Grantee:Felipe Xerez Cepêda Fonseca
Support Opportunities: Scholarships in Brazil - Doctorate