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Insulin-like growth factor-1 (IGF-1) plays an important role in exercise physiology. We aimed the present study at assessing whether IGF-1 system and its changes with exercise are related to walking capacity in intermittent claudication (IC).In 45 IC patients, blood samples for the measurement of IGF-1, IGF binding protein-3 (IGFBP-3), and acid labile subunit (ALS) were taken at rest and immediately after a treadmill exercise performed until initial claudication distance (ICD), i.e. until the occurrence of claudication pain in the affected limb. Control group consisted of 45 age- and sex-matched subjects without previous myocardial infarction or stroke.When IC patients were divided into two groups according to ICD value, ANOVA showed significant group differences for IGFBP-3 and ALS. Indeed, resting levels of IGFBP-3 were 3537+/-109 microg/L in controls, moderately lower (3399+/-204 microg/L) in IC patients with ICDor= median, and markedly lower (2580+/-196 microg/L) in those with ICDmedian. ANOVA showed a significant difference between the three groups (F=9.42, P=0.001). Corresponding values for ALS were 13.4+/-0.9 mg/L, 10.0+/-1.2 mg/L, and 5.9+/-0.7 mg/L (F=14.21, P=0.001). A similar trend was observed for IGF-1 (F=2.85, P=0.063). Also the subdivision of the IC population according to ankle/brachial index median value showed that values of IGFBP-3 and ALS resulted progressively lower as the severity of the disease increased (F=4.71, P=0.011 for IGFBP-3, and F=12.04, P=0.001, for ALS). Exercise significantly increased serum levels of the three components of the IGF-1 system. Furthermore, ICD showed a direct correlation with exercise-induced changes in serum levels of IGF-1 (r=0.465, P0.001), and ALS (r=0.624, P0.001). At multivariate analysis, ICD remained associated with both IGF-1 (beta-coefficient=0.513, P0.001), and ALS (beta-coefficient=0.645, P0.001), after correction for confounding factors.Impaired IGF-1 system is implicated in the complex mechanism responsible for reduced exercise tolerance in IC. Furthermore, this finding suggests that affected individuals could represent a target population for interventions to rise IGF-1 levels.