Celiprolol augments the effect of physical exercise on insulin sensitivityand serum lipid levels in chronic heart failure

Purpose: Impaired insulin sensitivity has been linked with chronic heart fa ilure (CHF). Exercise has a beneficial effect on insulin sensitivity in hea lthy subjects. It is used also as an adjunctive therapy in patients with CH F. We studied the effect of randomized treatment with celiprolol, a vasodil ating beta(1)-adrenoceptor antagonist, 200 mg once daily (n = 20) or placeb o (n = 11) on serum lipid levels and insulin sensitivity in patients with C HF. In addition, all subjects participated in a 6-month exercise training p rotocol. Thirteen subjects in the celiprolol and eight subjects in the cont rol group were on additional beta(1)-adrenoceptor antagonist as part of the ir tailored CHF therapy. Insulin sensitivity was determined using the hyper insulinemic euglycemic clamp test (diabetic subjects excluded, n = 11 for t he celiprolol group and n = 8 for the placebo group). Results: Insulin sens itivity index (ISI) increased by 33% (P < 0.05) in the celiprolol group and by 17% (NS) in the control group. The mean increase in the whole group was 20% [from 68.2 +/- 11.5 to 81.7 +/- 10.7 ml/min/kg (mU/l), P < 0.05]. No c hange was found in the total cholesterol level. HDL cholesterol levels incr eased by 12% (from 0.98 +/- 0.05 to 1.10 +/- 0.05 mmol/l, P < 0.005), and H DL/total cholesterol and HDL/LDL cholesterol ratios by 15% and 16%, respect ively (P < 0.005). The increase in serum fasting HDL cholesterol level was greater in the celiprolol-treated group (P < 0.05). At baseline ISI correla ted with maximal oxygen uptake (r = 0.65, P < 0.0001) and body mass index ( r = - 0.55, P < 0.001). The change in ISI correlated weakly with the improv ement in muscle exercise capacity (r = 0.53, P < 0.05). Conclusions: Insuli n sensitivity and serum lipid levels may be favorably affected by exercise training in subjects with mild-to-moderate CHF. Celiprolol, a vasodilating beta 1-selective adrenoceptor antagonist, potentiates this effect. (C) 2000 European Society of Cardiology. All rights reserved.