# Insulin resistance and metabolic health predict cardiorespiratory fitness: cohort study

## TL;DR

This study shows that insulin resistance and metabolic health are strong predictors of cardiorespiratory fitness, which is linked to overall mortality risk.

## Contribution

The study identifies insulin resistance as a key modifiable factor influencing cardiorespiratory fitness in individuals without cardiovascular disease.

## Key findings

- Insulin resistance, measured by QUICKI, explained up to 43% of VO2max variability.
- Higher BMI and fat mass were inversely associated with cardiorespiratory fitness.
- Insulin resistance reduces muscle glucose uptake and oxygen consumption during maximum effort.

## Abstract

Decreased cardiorespiratory fitness (CRF) is an all-cause mortality predictor. Oxygen consumption at peak exercise (VO2max) during a cardiopulmonary exercise test (CPET) is the gold standard for its evaluation. Since cardiometabolic risk factors reduce CRF, we aimed to assess the cardiopulmonary and metabolic responses during CPET and evaluate their determinants.

Subjects underwent incremental treadmill CPET and bioelectrical impedance analysis. Insulin sensitivity was estimated using the HOMA, QUICKI, and METS-IR indices. Multivariate regressions were used to evaluate determinants of VO2max. Nonlinearity was confirmed with an F-test between linear and polynomial models. Five hundred and three subjects were evaluated, 474 met maximum effort criteria, (64% females). Median age was 4(26–52); 41% had normal weight, 33% overweight, 26% obesity. Prevalence of insulin resistance ranged from 22% to 46%, depending on the equation used. VO2max was 29.8(24–36) and 36.6 (30.6–43.3) mL/kg/min for females and males. Body composition analysis revealed that a higher BMI exhibited strong biological collinearity with metrics associated with adiposity excess and was inversely associated with CRF. After adjusting for age, sex, BMI, and fat mass, insulin resistance evaluated by QUICKI explained up to 43% of VO2max variability and was inversely associated with CRF.

In a cohort of individuals without established CVD, the main determinants of CRF were modifiable risk factors associated with excess adiposity and insulin resistance. The potential mechanisms underlying the reduction in CRF include decreased relative muscle mass and insulin resistance, which reduce muscle glucose uptake and O2 consumption during maximum effort, where anaerobic glycolysis plays a central role.

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