CHF NOVEMBER/DECEMBER 2003 FRONTIERS IN CHF 347 Abstract. Objective . This study sought to test whether insulin improves exercise ventilatory effi- ciency (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 efficiency and peak Vo 2 (cycle ergometry ramp protocol), as well as DL CO at rest and its subdivisions (membrane con- ductance [D M ] and pulmonary capillary blood vol- ume [V C ]), were assessed in 18 patients with type 2 diabetes-HF comorbidity at baseline and after 50 mL saline plus regular insulin (10 IU) or saline was infused on consecutive days, according to a random crossover design. Glycemia was kept at a preinsulin 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 measure- ments performed in the 60 minutes after infusions, compared with at baseline, saline was ineffective, whereas insulin augmented peak Vo 2 (+13.5%) low- ered 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 ejec- tion fraction at rest. Changes in peak Vo 2 and VE/VCO 2 slope (r=0.67, p=0.002; R=-.73, p<0.001, respectively) correlated with those in DL CO . These re- sponses were unrelated to glycohemoglobin and base- line fasting blood sugar. They were persistent at 6 hours after insulin infusion and were undetectable at 24 hours. Conclusion. In diabetes–HF comorbidity, insulin causes a prolonged improvement in physical per- formance through activation of multiple factors, among which facilitation of gas conductance seems to be predominant.—Guazzi M, Tumminello G, Mat- turri M, et al. Insulin ameliorates exercise ventilatory ef- ficiency and oxygen uptake in patients with heart fail- ure-type 2 diabetes comorbidity. J Am Coll Cardiol. 2003;42:1044–1050. Comment. This research looked at the role of insulin in treating patients with heart failure and coexistent di- abetes mellitus and assessed whether insulin improves exercise performance in patients with heart failure and coexisting diseases and whether improved alveolar–capillary membrane exchange has a role in these effects. Eighteen patients with type 2 diabetes mellitus, New York Heart Association (NYHA) class II- III congestive heart failure, ejection fraction (EF) <35%, and ability to complete a maximal cardiopul- monary exercise test were included. Patients with hy- pertension, pulmonary disease, or smoking >10 ciga- rettes per day during past 5 years; exercise limited by symptoms other than dyspnea or fatigue; ECG changes on effort; clinically evident distal symmetrical neuropa- thy, autonomic insufficiency, or renal impairment; and Frontiers in Congestive Heart Failure David Tepper, MD Editor Insulin Ameliorates Exercise Ventilatory Efficiency and Oxygen Uptake in Patients With Heart Failure-Type 2 Diabetes Comorbidity www.lejacq.com ID: 2318 Mini Kamboj, MD; Sricharan Kantipudi, MD; Atul Khasais, MD; R. K. Thakur, MD From the Department of Medicine, Michigan State University, East Lansing, MI 48824