Cardiorespiratory fitness and the metabolic syndrome: Roles of inflammation and abdominal obesity

Abstract

Objective: Individuals with metabolic syndrome have increased risk of type 2 diabetes and cardiovascular disease. We aimed to test the hypothesis that a high level of cardiorespiratory fitness (CR-fitness), counteracts accumulation of visceral fat, decreases inflammation and lowers risk factors of the metabolic syndrome.

Method: The study sample included 1,293 Danes (age 49-52 years) who from 2009 to 2011 participated in the Copenhagen Aging and Midlife Biobank, including a questionnaire, physical tests, and blood samples. Multiple linear regression models were performed with CR-fitness as exposure and plasma levels of cytokines and high sensitive C-reactive protein as outcomes and measures of abdominal obesity were added to test if they explained the potential association. Similarly, multiple linear regression models were performed with CR-fitness as exposure and factors of the metabolic syndrome as outcomes and the potential explanation by inflammatory biomarkers were tested. All models were adjusted for the effect of age, sex, smoking, alcohol consumption, socio-economic status, and acute inflammatory events within the preceding two weeks.

Results: CR-fitness was inversely associated with high sensitive C-reactive protein, Interleukin (IL)-6, and IL-18, and directly associated with the anti-inflammatory cytokine IL-10, but not associated with tumor necrosis factor alpha, interferon gamma or IL-1β. Abdominal obesity could partly explain the significant associations. Moreover, CR-fitness was inversely associated with an overall metabolic syndrome score, as well as triglycerides, glycated haemoglobin A1c, systolic blood pressure, diastolic blood pressure and directly associated with high-density lipoprotein. Single inflammatory biomarkers and a combined inflammatory score partly explained these associations.

Conclusion: Data suggest that CR-fitness has anti-inflammatory effects that are partly explained by a reduction in abdominal obesity and a decrease in the metabolic syndrome risk profile. The overall inflammatory load was mainly driven by high sensitive C-reactive protein and IL-6.

Fig 1. Associations between cardiorespiratory fitness (CR-fitness) and inflammatory biomarkers.

Multiple linear regression analyses were performed with CR-fitness as exposure and plasma levels of inflammatory biomarkers as outcomes, adjusted for the effect of age, sex, social class, alcohol consumption, smoking status and acute inflammatory events. Relative differences (%) in estimates of inflammatory biomarkers, adjusted for measures of abdominal obesity. Y-axis: Regression estimates of inflammatory biomarkers from models containing abdominal obesity have been normalised to estimates from the initial model (100%) to show relative percentage changes. P<0.05 on all regression estimates shown. Waist = waist circumference; WHtR = waist-to-height-ratio; WHR = waist-hip-ratio; trunk fat% = truncal fat percentage; MS = metabolic syndrome.

Fig 2. Associations between cardiorespiratory fitness (CR-fitness) and factors of the metabolic syndrome.

Multiple linear regression analyses were performed with CR-fitness as exposure and factors of the metabolic syndrome as outcomes, adjusted for the effect of age, sex and social class, alcohol consumption, smoking status. Relative difference (%) in estimates of factors of the metabolic syndrome, adjusted for measures of inflammation Y-axis: Regression estimates of metabolic syndrome factors from models containing inflammation have been normalised to estimates from the initial model (100%) to show relative percentage changes. P<0.01 on all regression estimates shown. Inflammatory load is a combined score of hsCRP, IL-6, IL-18 and IL-10.