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The prevalence of diabetes mellitus (DM) in the United States has been rising since 1990. In 2018, 34.2 million people, around 10.5% of the US population, had DM (11% of men, 9.5% of women) [1]. In 2016, it was estimated that 91.2% of adults with DM have type 2 diabetes (T2D) [2] and the prevalence of youth-onset T2D is also rising [1]. DM and its related health complications, including cardiovascular disease (CVD), chronic kidney disease (CKD), and congestive heart failure (CHF), are associated with significant morbidity and mortality. People with DM accounted for 7.8 million hospital discharges in 2016 with 1.7 million of these hospitalizations due to major CVD events [1]. Additionally, premature mortality from CVD is 2- to 6-fold greater in people with DM than for people without diabetes [3]. Lower levels of cardiorespiratory fitness (CRF), measured as maximal oxygen consumption (VO2max), are predictive of greater short-term mortality risk in adults and children with DM [4-6], as in the general population [7-9]. Lower CRF in people with DM has also been associated with future CVD events and as such is an important modifiable CV risk factor [10-12]. In a study by Seyoum et al., men and women with diabetes who developed CVD events within 5 years had lower baseline peak VO2 than those who did not have CVD events during this follow-up period [10].

Compared with healthy individuals without diabetes, CRF is lower in adults and children with T2D and in children with type 1 diabetes, even in the absence of clinically apparent CVD in either group. These findings were observed in individuals with similar habitual physical activity levels, age, pubertal stage (for youth), and body mass index (BMI) (Table 1) [13-19]. Additionally, the presence of T2D confers a greater CRF deficit in women than in men [15, 20]. Not only does lower CRF predict premature mortality, it may lead to barriers to exercise recommendations by raising the relative intensity of a given work rate [21]. Potential physiological mechanisms that may contribute to lower CRF in people with T2D include insulin resistance and mitochondrial, vascular, and cardiac dysfunction. This review will focus on how each of these factors may contribute to CRF impairment in T2D and conclude with an assessment of the current state of knowledge about sex differences in CRF in people with T2D.

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