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J Am Coll Cardiol, 2003; 42:1044-1050, doi:10.1016/S0735-1097(03)00914-8
© 2003 by the American College of Cardiology Foundation
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CLINICAL RESEARCH: HEART FAILURE/CARDIAC TRANSPLANTATION

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

Marco Guazzi, MD, PhD, FACC*,*, Gabriele Tumminello, MD*, Marco Matturri, MD{dagger} and Maurizio D. Guazzi, MD, PhD{dagger}

* Department of Medicine and Surgery, University of Milan, Cardiology Division, San Paolo Hospital, Milan, Italy
{dagger} Institute of Cardiology, University of Milan, Milan, Italy

* Reprint requests and correspondence: Dr. Marco Guazzi, Cardiopulmonary Laboratory, Cardiology Division, University of Milano, San Paolo Hospital, Via A. di Rudini 8, 20142 Milano, Italy.
Marco.Guazzi{at}unimi.it

Presented in part at the 75th American Heart Association Scientific Sessions, Chicago, November 16–20, 2002.

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.

Abbreviations and Acronyms
  DLCO
  lung diffusing capacity for carbon monoxide
  DM
  alveolar–capillary membrane diffusion capacity
  HF
  heart failure
  peak VO2
  oxygen consumption at peak exercise
  VA
  alveolar volume
  VC
  pulmonary capillary blood volume available for gas exchange
  VCO2
  carbon dioxide production
  VE/VCO2 slope
  slope of the increase in ventilation with respect to carbon dioxide production
  VO2
  oxygen uptake
  VO2 AT
  oxygen consumption at the anaerobic threshold
  {Delta}VO2/{Delta}WR
  rate of oxygen consumption increase per work rate




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