Natriuretic peptides as a possible mediator of positive effects of exercise training in patients with the metabolic syndrome: a randomized controlled clinical trial

Abstract

Background: Natriuretic Peptides are a group of peptide-hormones that are well known for their role in cardiovascular homeostasis. During the last decade, a wide range of novel findings about natriuretic peptides proves that NPs have also an active role in the defense against metabolic disease. NPs have been found to prevent the accumulation of fatty acids, to favorably affect adipose tissue distribution and to increase the basal metabolism trough many mechanisms. On the other hand, evidence has shown obesity and insulin resistance to be associated with lower levels of circulating natriuretic peptides. Thus, people with this metabolic profile, as patients with metabolic syndrome, could be stuck in a vicious cycle in which a suppressed natriuretic peptide system leads to the impairment in the ability to resist fat accumulation and insulin resistance. Therefore, any measure that could help to increase circulation and action of NPs could help to break this cycle, improving the metabolic profile. Fortunately, a number of novel stimuli have been described like weight loss or exercise, suggesting the possibility that the natriuretic peptide system could contribute to the favorable metabolic effects of exercise. Objective: the main objective of this study is to evaluate if a 2-month moderate-intensity exercise training intervention leads to an increase in NT-ProBNP circulating levels in patients with metabolic syndrome and a sedentary lifestyle in order to study if positive effects of exercise training in metabolic syndrome may partially due to Natriuretic Peptides actions. Methods: This study will be a controlled, randomized and single-center clinical trial. It will be an open study, but observer blind will be done. This study will be set in Hospital Santa Caterina, in the Sports Medicine Department and patient sampling will take place in the CAP of the 4 ABS of the city of Girona. The recruitment will be based on a consecutive non-probabilistic sampling method. The participants will be 66 patients (from 18 to 65 years old) with metabolic syndrome, defined as the current criteria of the NCEP ATP III, and a sedentary lifestyle at baseline. The patients will be randomly divided in two groups of 33 patients (1:1). The first group will go under a 2- month moderate-intensity exercise training program and the second group will be the control group that will maintain their baseline sedentary lifestyle. The main dependent variable will be the increase in NT-proBNP blood circulating levels in the exercise group, comparing to the control group, and it will be measured at baseline and at the end of the intervention by electrochemiluminescence immunoassay. Secondary dependent variables will be the metabolic syndrome components, the insulin resistance condition and the subjects cardiovascular fitness. The results will be expressed as percentages for categorical variables and as the mean±standard deviation for continuous variables. A bivariate analysis will be also performed using a Student test to compare continuous variables and a Chi test for categorical variables