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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 and Maurizio D. Guazzi, MD, PhD

^* Department of Medicine and Surgery, University of Milan, Cardiology Division, San Paolo Hospital, Milan, Italy
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 (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/VCO₂ 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.

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   VO2/WR   rate of oxygen consumption increase per work rate

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