title: Celiprolol augments the effect of physical exercise on insulin sensitivity and serum lipid levels in chronic heart failure.
abstract: OBJECTIVE
  Impaired insulin sensitivity has been linked with chronic heart failure (CHF). Exercise has a beneficial effect on insulin sensitivity in healthy subjects. It is used also as an adjunctive therapy in patients with CHF. We studied the effect of randomized treatment with celiprolol, a vasodilating beta(1)-adrenoceptor antagonist, 200 mg once daily (n=20) or placebo (n=11) on serum lipid levels and insulin sensitivity in patients with CHF. In addition, all subjects participated in a 6-month exercise training protocol. Thirteen subjects in the celiprolol and eight subjects in the control group were on additional beta(1)-adrenoceptor antagonist as part of their tailored CHF therapy. Insulin sensitivity was determined using the hyperinsulinemic euglycemic clamp test (diabetic subjects excluded, n=11 for the celiprolol group and n=8 for the placebo group).
  
  
  RESULTS
  Insulin sensitivity 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 change was found in the total cholesterol level. HDL cholesterol levels increased by 12% (from 0.98+/-0.05 to 1.10+/-0.05 mmol/l, P<0. 005), and HDL/total cholesterol and HDL/LDL cholesterol ratios by 15% and 16%, respectively (P<0.005). The increase in serum fasting HDL cholesterol level was greater in the celiprolol-treated group (P<0.05). At baseline ISI correlated 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 improvement in muscle exercise capacity (r=0.53, P<0.05).
  
  
  CONCLUSIONS
  Insulin sensitivity and serum lipid levels may be favorably affected by exercise training in subjects with mild-to-moderate CHF. Celiprolol, a vasodilating beta1- selective adrenoceptor antagonist, potentiates this effect.
authors.affiliation: Department of Medicine, Turku University Central Hospital, Kiinamyllynk 4-8, 20520, Turku, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Pietilä
authors.forename: K
authors.initials: K
authors.lastname: Malminiemi
authors.forename: R
authors.initials: R
authors.lastname: Huupponen
authors.forename: J
authors.initials: J
authors.lastname: Rouru
authors.forename: K
authors.initials: K
authors.lastname: Pulkki
authors.forename: E
authors.initials: E
authors.lastname: Pere
authors.forename: L M
authors.initials: LM
authors.lastname: Voipio-Pulkki
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D017272:Celiprolol / Q000494:pharmacology*; D008076:Cholesterol, HDL / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood*; D015444:Exercise / Q000502:physiology*; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000503:physiopathology*; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D008875:Middle Aged; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D000319:Adrenergic beta-Antagonists; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014665:Vasodilator Agents; D017272:Celiprolol