Relationship between insulin-like growth factor-1 system and exercise tolerance in patients with intermittent claudication.
OBJECTIVE
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).


METHODS
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.


RESULTS
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 ICD >or= median, and markedly lower (2580+/-196 microg/L) in those with ICD<median. 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, P<0.001), and ALS (r=0.624, P<0.001). At multivariate analysis, ICD remained associated with both IGF-1 (beta-coefficient=0.513, P<0.001), and ALS (beta-coefficient=0.645, P<0.001), after correction for confounding factors.


CONCLUSIONS
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.
Laurenzano
E
E
Department of Clinical Medicine, University of Naples Federico II, Naples, Italy.
Brevetti
G
G
Lanero
S
S
Brevetti
L
L
Colao
A
A
Chiariello
M
M
D055109:Ankle Brachial Index; D015415:Biomarkers / Q000097:blood; D002352:Carrier Proteins / Q000097:blood; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005080:Exercise Test; D017079:Exercise Tolerance; D005260:Female; D006023:Glycoproteins / Q000097:blood; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007383:Intermittent Claudication / Q000097:blood* / Q000503:physiopathology*; D007558:Italy; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016138:Walking
D015415:Biomarkers; D002352:Carrier Proteins; D006023:Glycoproteins; C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; C075944:insulin-like growth factor binding protein, acid labile subunit; D007334:Insulin-Like Growth Factor I