Insulin ameliorates exercise ventilatory efficiency and oxygen uptake in patients with heart failure–type 2 diabetes comorbidity

Objectives This study sought to test whether insulin improves exercise ventilatory efficiency (VE/VCO2 slope) and oxygen uptake at peak exercise (peak VO2) in patients with type 2 diabetes–heart failure (HF) comorbidity. Background In type 2 diabetes–HF comorbidity, depression of alveolar–capillary diffusion (DLCO) correlates with deterioration of exercise VE/VCO2 slope and peak VO2. Insulin potentiates DLCO in these patients. Methods Exercise ventilatory efficiency and peak VO2 (cycle ergometry ramp protocol), as well as DLCO at rest and its subdivisions (membrane conductance [DM] and pulmonary capillary blood volume [VC]) were assessed in 18 patients with type 2 diabetes–HF comorbidity at baseline and after 50 ml of saline + regular insulin (10 IU), or saline, was infused on consecutive days, according to a random crossover design. Glycemia was kept at pre-insulin level for the experiment duration. Results Baseline DLCO, DM, peak VO2, and VE/VCO2 slope were compromised in these patients. At measurements performed in the 60 min after infusions, compared with at baseline, saline was ineffective, whereas insulin augmented peak VO2 (+13.5%) and lowered VE/VCO2 slope (−18%), and also increased time to anaerobic threshold (+29.4%), maximal O2 pulse (+12.3%), aerobic efficiency (+21.2%), DLCO (+12.5%), and DM (+21.6%), despite a reduction in VC (−16.3%); insulin did not vary cardiac index and ejection fraction at rest. Changes in peak VO2 and VE/VCO2 slope (r = 0.67, p = 0.002; r = −0.73, p < 0.001, respectively) correlated with those in DLCO. These responses were unrelated to glycohemoglobin and baseline fasting blood sugar. They were persistent at 6 h after insulin infusion, and were undetectable at 24 h. Conclusions In diabetes–HF comorbidity, insulin causes a prolonged improvement in physical performance through activation of multiple factors, among which facilitation of gas conductance seems to be predominant.