Peripheral Oxygen Extraction and Exercise Limitation in Asymptomatic Patients with Diabetes Mellitus

Patients with diabetes mellitus (DM) frequently present reduced exercise capacity. We aimed to explore the extent to which peripheral extraction relates to exercise capacity in asymptomatic patients with DM. We prospectively enrolled 98 asymptomatic patients with type-2 DM (mean age of 59 ± 11 years and 56% male sex), and compared with 31 age, sex and body mass index-matched normoglycemic controls. Cardiopulmonary exercise testing with resting followed by stress echocardiography was performed. Exercise response was assessed using peak oxygen uptake (peak VO₂) and ventilatory efficiency was measured using the slope of the relationship between minute ventilation and carbon dioxide production (VE/VCO₂). Peripheral extraction was calculated as the ratio of VO₂ to cardiac output. Cardiac function was evaluated using left ventricular longitudinal strain, E/e', and relative wall thickness. Among patients with DM, 26 patients (27%) presented reduced percent-predicted-peak VO₂(<80%) and 18 (18%) presented abnormal VE/VCO₂slope (>34). There was no significant difference in peak cardiac output; however, peripheral extraction was lower in patients with DM compared to controls. Higher peak E/e' (beta = -0.24, p = 0.004) was associated with lower peak VO₂ along with age, sex and body mass index (R² = 0.53). A cluster analysis found left ventricular longitudinal strain, E/e', relative wall thickness and peak VO₂ in different clusters. In conclusion, impaired peripheral extraction may contribute to reduced peak VO₂in asymptomatic patients with DM. Furthermore, a cluster analysis suggests that cardiopulmonary exercise testing and echocardiography may be complementary for defining subclinical heart failure in patients with DM.