Mechanistic Causes of Reduced Cardiorespiratory Fitness in Type 2 Diabetes

Abstract

<jats:title>Abstract</jats:title> <jats:p>Type 2 diabetes (T2D) has been rising in prevalence in the United States and worldwide over the past few decades and contributes to significant morbidity and premature mortality, primarily due to cardiovascular disease (CVD). Cardiorespiratory fitness (CRF) is a modifiable cardiovascular (CV) risk factor in the general population and in people with T2D. Young people and adults with T2D have reduced CRF when compared with their peers without T2D who are similarly active and of similar body mass index. Furthermore, the impairment in CRF conferred by T2D is greater in women than in men. Various factors may contribute to this abnormality in people with T2D, including insulin resistance and mitochondrial, vascular, and cardiac dysfunction. As proof of concept that understanding the mediators of impaired CRF in T2D can inform intervention, we previously demonstrated that an insulin sensitizer improved CRF in adults with T2D. This review focuses on how contributing factors influence CRF and why they may be compromised in T2D. Functional exercise capacity is a measure of interrelated systems biology; as such, the contribution of derangement in each of these factors to T2D-mediated impairment in CRF is complex and varied. Therefore, successful approaches to improve CRF in T2D should be multifaceted and individually designed. The current status of this research and future directions are outlined.</jats:p>

Prognostic value of exercise capacity in incident diabetes: a country with high prevalence of diabetes

“…It is thought to be mediated by positive changes in the human body tissue profile, reduced adiposity[ 13 ], and an immediate increase in insulin sensitivity and glucose disposal[ 14 ]. However, several studies have shown that impaired oxidative respiration due to mitochondrial dysfunction[ 15 ] underlies the pathogenesis of diabetes reflecting a native genetic state independent of physical activity[ 16 ].…”

“…It is thought to be mediated by positive changes in the human body tissue profile, reduced adiposity [13], and an immediate increase in insulin sensitivity and glucose disposal [14]. However, several studies have shown that impaired oxidative respiration due to mitochondrial dysfunction [15] underlies (continued) Table 1 the pathogenesis of diabetes reflecting a native genetic state independent of physical activity [16]. Scattered small cross-sectional studies have shown that exercise capacity is inversely associated with impaired glycemic control [17], the metabolic syndrome [18], diabetes [19] and positively associated with glucose disposal rate and insulin sensitivity [20].…”

Canagliflozin Prevents Hyperglycemia-Associated Muscle Extracellular Matrix Accumulation and Improves the Adaptive Response to Aerobic Exercise

“…The mechanisms that lead to hyperglycemia-associated decreases in VO 2peak are incompletely understood. However, low VO 2peak in people with diabetes has been linked with altered function of skeletal muscle, including low muscle blood flow and oxidative capacity ( 16 – 20 ). Our data from rodent models of hyperglycemia demonstrate that blunted improvements in VO 2peak are associated with impaired remodeling of skeletal muscle toward an aerobic phenotype, leading to lower capillary density and fewer oxidative fibers ( 15 ).…”

The Role of Cardiorespiratory Fitness in Children with Cardiovascular Risk

“…People with diabetes mellitus type 2 have reduced cardiorespiratory fitness compared to healthy controls, with an association to increased cardiovascular morbidity and mortality. The mechanisms of lower cardiorespiratory fitness in children with diabetes mellitus type 2 are multifaceted and involve interrelated defects in insulin action, mitochondrial dysfunction, skeletal muscle microvasculature, and cardiac dysfunction [55]. In youth with diabetes mellitus type 2, left ventricular size is clearly related to physical fitness, which might counteract adverse effects of poor glycaemic control and, at least according to the study, right ventricular function [56].…”