• aerobic capacity
• cardiovascular fitness
• diabetic cardiomyopathy
• exercise intolerance
• exercise physiology
• oxygen uptake
• type 2 diabetes

Background and aim. The association between type 2 diabetes mellitus (T2DM) and heart failure is well established. Early in the course of the disease, some degree of impaired exercise capacity (the hallmark of heart failure and a powerful marker of health status with prognostic value) can be frequently highlighted in otherwise asymptomatic T2D subjects, but the pathophysiologic mechanisms are far from being clear. The study aims at determining the pathophysiological determinants of reduced peak oxygen uptake (VO2peak) in T2DM.
Methods. We prospectively enrolled T2DM patients from the Diabetology outpatient clinic, who underwent baseline metabolic and cardiovascular characterization (ECG, echocardiogram, routine biochemistry), screening for macro- and micro-angiopathic complications, and imaging-cardiopulmonary exercise testing (iCPET). The population was then divided in two groups by the presence or absence of exercise intolerance, defined as a VO2peak >80% of maximal theorical oxygen uptake (VO2max).
Results. 88 patients in good glycemic control and free from complications completed the study, all performing a maximal iCPET, reaching a maximal respiratory exchange ratio. 48 patients (55%) showed exercise intolerance with VO2peak <80% of VO2max. This group showed a reduced peripheral oxygen extraction at peak exercise despite a comparable cardiac output, a reduced VO2/work slope, greater prevalence of chronotropic insufficiency, as well as a reduced systolic reserve as measured through the increase in 2D left ventricle ejection fraction, tissue-Doppler derived S’ and speckle-tracking derived global longitudinal strain. Diastolic dysfunction, vascular resistances, endotherlial function, and pulmonary function indices did not differ between the two groups. At the multivariate linear regression model, peripheral oxygen extraction and systolic reserve predicted the VO2peak.
Conclusions. Exercise intolerance is frequent in the T2DM otherwise asymptomatic population, and is seemingly driven mainly by an impaired peripheral oxygen extraction coupled with a subclinical left ventricular systolic dysfunction. The use of the iCPET might be a useful tool for diagnosing incident HF and in possibly in its primary prevention in T2DM.