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

J Am Coll Cardiol. 2003 Sep 17;42(6):1044-50. doi: 10.1016/s0735-1097(03)00914-8.


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 (DL(CO)) correlates with deterioration of exercise VE/VCO2 slope and peak VO2. Insulin potentiates DL(CO) in these patients.

Methods: Exercise ventilatory efficiency and peak VO2 (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 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/VCO(2) slope (-18%), and also increased time to anaerobic threshold (+29.4%), maximal O2 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 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 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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cross-Over Studies
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Exercise*
  • Female
  • Heart Failure / complications*
  • Heart Failure / physiopathology*
  • Humans
  • Insulin / therapeutic use*
  • Male
  • Middle Aged
  • Oxygen Consumption* / drug effects
  • Pulmonary Ventilation* / drug effects


  • Insulin