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/VCO 2 slope) and oxygen uptake at peak exercise (peak VO 2) in patients with type 2 diabetes-heart failure (HF) comorbidity. BACKGROUND: In type 2 diabetes-HF comorbidity, depression of alveolar-capillary diffusion (DL CO) correlates with deterioration of exercise VE/VCO 2 slope and peak VO 2. Insulin potentiates DL CO in these patients. METHODS: Exercise ventilatory effidency and peak VO 2 (cycle ergometry ramp protocol), as well as DL CO at rest and its subdivisions (membrane conductance [D M] and pulmonary capillary blood volume [V C]) 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 DL CO, D M, peak VO 2, and VE/VCO 2 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 VO 2 (+13.5%) and lowered VE/VCO 2 slope (-18%), and also increased time to anaerobic threshold (+29.4%), maximal O 2 pulse (+12.3%), aerobic efficiency (+21.2%), DL CO (+12.5%), and D M (+21.6%), despite a reduction in V C (-16.3%); insulin did not vary cardiac index and eiecdon fraction at rest. Changes in peak VO 2 and VE/VCO 2 slope (r = 0.67, p = 0.002; r = -0.73, p < 0.001, respectively) correlated with those in DL CO. 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.