Fig. 3.

Proposed intervention trials. Four proposals for pharmacological interventions that could help address the relative importance of individual organ contributions to exercise intolerance in type 2 diabetes are here schematized. Grey vertical arrows indicate either enhancement (arrows facing up) or inhibition (arrows facing down) by the pharmacological treatment on the target organ. The red lines represent diabetic subjects and the blue ones the controls. The cardiopulmonary exercise test variables that investigate the organs implicated (schematized on top of each graphic) are qualitatively showed in the graphic on the left side of each subsection, while on the right there is the effect that we could expect if the organ schematized is the principal responsible for the impairment in the variable outlined (the gap between diabetic and non-diabetic patients is reduced or abolished). The Asterix (*) indicates the difference between these two populations, based on literature review. a The use of positive inotropes -like dobutamine- could confirm the weight of a reduced stroke work on oxygen uptake per heartbeat if a normalization is observed. b Muscle perfusion enhancers -like dipyridamole- could highlight the contribution of skeletal muscle vasculature adjustments by ameliorating oxygen uptake. c By reducing a hyperactive sympathetic restrain, sympathetic inhibitors might ameliorate cardiovascular adjustments and thus oxygen assumption, confirming the role of autonomic imbalance in exercise intolerance. d Anticholinergic bronchodilators could normalize “ventilatory efficiency” by facilitating the reduction of physiological dead space if the latter is due to bronchial cholinergic hyperactivation. VO₂, oxygen uptake, VO₂/HR, oxygen pulse; VE, ventilation