Preventing Metabolic Syndrome in Patients With Morbid Obesity by Resistance Training: Reporting Non-responder Prevalence
Phase: NA
Conditions: Morbid Obesity, Obesity, Physical Activity, Metabolic Syndrome, Risk Factor, Cardiovascular
Sponsor: Universidad de Los Lagos

Title: PREVENTING METABOLIC SYNDROME IN MORBID 
OBESITY WITH RESISTANCE TRAINING: REPORTING NON-RESPONDER 
PREVALENCE   
ID: RP08042019 
DATE: April 11, 2019 
 
Study Documents 
Scientific background: The prevalence of metabolic syndrome (MetS) and 
cardiovascular disease is expected to rise along with the global obesity epidemic [1]. 
MetS is a cluster of clinical risk factors, including abdominal (visceral) obesity, 
hypertension, elevated serum triglycerides, low serum high-density lipoprotein (HDL) 
and hyperglycaemia [2]. Additionally, MetS is also associated with a pro-inflammatory 
state that leads to an altered physiological balance of adipokines, insulin resistance, 
endothelial dysfunction and a pro-atherogenic state [3], that increase the cardiovascular 
risk when population have more fat as the obesity state [4]. The morbid obesity is 
considered as a chronic disease highly-related with MetS development [5]. The MetS for  
example, significantly decreases the life expectancy of individuals with morbid obesity 
[4] and increases the disease burden and economic costs associated with healthcare [6]. 
In this sense, more recently, there was reported that body mass index (BMI) and fat 
distribution showed higher associations with inflammation, fat indices, and more 
prevalence of MetS in morbidly obese subjects [7], claiming for an early prevention of 
the MetS in the morbid obese state. Exercise training has proven to be effective in 
inducing a clinically significant weight loss and reducing cardiovascular risk [8]. Exercise  
have reported to be associated with increased muscle mass, decreased body fat, and 
improved metabolic profile (i.e., improved glucose control and lipid levels) [9].  

Additionally, exercise training in MetS patients was also associated with a 
significant reduction in high-sensitivity C reactive protein, and insulin resistance, but 
independent of weight loss [10], being this last effect (i.e., weight loss) a non-necessary 
aim into morbid obese patients. However, considering that the cardiorespiratory fitness 
(CRF) have been reported to be a strong predictor of overall health, exercise training may 
improve CRF in patients with MetS [11, 12], and thus we speculate that the CRF related 
outcomes such as the walking perform can be relevant for the health in obese patients at 
risk of MetS. Additionally, the resistance exercise training (RT, i.e., a particular exercise 
training modality consisting in stimulating muscles using external weights), may help to 
reduce health markers as systolic blood pressure (SBP) in obese patients with MetS risk 
factors [13]. In addition, supervised RT improved muscle strength and functional capacity 
in patients with obesity undergoing bariatric surgery [14]. However, although RT has 
been widely studied in obesity [15], there is little information in the morbid obesity. On 
the other hand, there is poor knowledge similarly, about the interindividual variability to  
exercise training in terms of responders and non-responders (NR). For example, as in 
reducing fat markers, we have shown that more baseline fat (overweight, obesity) have 
showed higher fat decreases and thus less NR, we speculate that morbid obese patients 
could decrease more both fat and MetS markers than other peers with less fat as those 
with obesity. Objectives: to determine the effects of a resistance training programme (RT) 
in preventing or attenuating metabolic syndrome (MetS) in patients with morbid obesity. 
A second aim was to report the prevalence of NR in terms of improvements in MetS 
markers and other co-variables considered. Design: An experimental, and non-
randomized control clinical study. Methods: In an experimental clinical trial, obese and  
morbid obese patients will be invited for participaiting in a lifestyle study including 
resistant training during 20 weeks for preventing MetS in this cohort. Participants will be  

recruited from the morbid obesity (Temuco, Chile), during two months by phone 
invitation. The sample size will be determined in accordance with the study’s feasibility  
recruitment, and a previous pilot study where it was determined the effects of a RT 
programme on anthropometric parameters, muscle function and metabolic profile and 
nutritional in the potential morbid obese patients [8]. The study will be completed in 
accordance with the Declaration of Helsinki and was approved by the Ethical Committee  
of the Universidad de La Frontera, Temuco, Chile. Patients and Recruitment: The 
inclusion criteria will be as follows: i) older than 18 and younger and =65 years of age 
(i.e., 65 y is the retirement age in women in Chile), ii) daily activities including walking,  
physical autonomy, iii) medical authorization by a physician, and iv) body mass index 
(BMI) =35 kg/m2, according to BMI, general population is classified: class II obesity 
(BMI =35.0-39.9 kg/m2), class III - extreme obesity or mobid obesity (BMI =40 kg/m2)  
[16, 17]. Exclusion criteria will be: i) physical limitations (e.g., restricting injuries of the  
musculoskeletal system, or dependent of a third person), ii) exercise-related dyspnoea or  
respiratory alterations, iii) chronic heart disease with any worsening in the last month, 
and iv) an adherence rate of less than 80% of the total interventions (excluded from the  
statistical analyses).  
 
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Statistical Analysis Plan (SAP): We will apply 2 main forms of statistical analyses a) to  
report the pre-post changes in mean terms, and b) to report the results according with the  
inter-individual responses based on the technical error criteria, where according with the  
error calculated in the three previous measurements registered by the sample that was 
voluntary. Thus, for example, we will classify the subjects in responders and non-
responders by the technical error of measurement, and additionally, we will classify the 
subjects according with a responder and non-responder clinical criteria, where we will 
classify as responders to all subjects who can be able of changing an initial adverse 
clinical altered profile for a healthy new classification. Thus, the specific statistical 
methods that we hope to apply for each analysis are; test of normality and 
homoscedasticity assumptions using Shapiro-Wilk and Levene’s tests, the Student’s t test  
for the identification of differences at baseline. An ANCOVA will be conducted (for 
potential confounders outcomes) in those altered baseline differences outcomes. We also  
hope to apply the repeated measures of two-way (group, time) to assess occurrence of an  
actual training effect [i.e., p <0.05 for the interaction (group × time) for the different study  
outcomes]. Among the specific statistical methods we hope to apply the Bonferroni post  
hoc test we hope to apply when we can be seen test differences among groups. Similarly,  
we hope to apply the Cohen’s d test in order to detect effect size, using the threshold 
values of 0.20, 0.60, 1.2, and 2.0 for small, moderate, large, and very large effects, 
respectively [18], with 95% confidence intervals (CI). The alpha level was fixed at P<0.05 
for statistical significance.