Circulating IGF binding protein-1 is inversely associated with leptin in non-obese men and obese postmenopausal women.
OBJECTIVE
Hyperleptinaemia and hyperinsulinaemia interrelate to insulin-like growth factor binding protein 1 (IGFBP-1), and disturbances in the growth hormone-IGF-I axis are linked to obesity and cardiovascular diseases. However, whether the association between leptin and the GH-IGF-I axis is altered with increasing obesity is not known. We therefore examined the relationship between leptin, IGF-I, IGFBP-1, insulin and proinsulin in men and women with or without obesity in a population study.


METHODS
Healthy subjects (n=158; 85 men and 73 pre- and postmenopausal women) from the Northern Sweden MONICA (Monitoring of Trends and Determinants in Cardiovascular Disease) population were studied with a cross-sectional design.


METHODS
Anthropometric measurements (body mass index (BMI) and waist circumference) and oral glucose tolerance tests were performed. Radioimmunoassays were used for the analyses of leptin, IGF-I and IGFBP-1, and ELISAs for specific insulin and proinsulin.


RESULTS
Leptin inversely correlated to IGFBP-1 in non-obese men (P<0.05) and obese postmenopausal women (P<0.05). In contrast, leptin did not correlate to IGF-I. IGFBP-1 was also significantly associated with proinsulin in non-obese men (P<0.01) and non-obese premenopausal women (P<0.05). The association between leptin and IGFBP-1 was lost after adjustment for insulin. In multivariate analyses taking measures of adiposity into account, low proinsulin, and IGF-I in combination with old age, but not leptin, predicted high IGFBP-1 levels.


CONCLUSIONS
Leptin was inversely associated with IGFBP-1 in non-obese men and obese postmenopausal women, and proinsulin was inversely associated with IGFBP-1 in non-obese men and premenopausal women. However, these associations were lost with increasing central obesity in men and premenopausal women and after control for insulin. Therefore, this study suggests (i) that leptin is of minor importance for regulation of IGFBP-1 levels and (ii) that the insulin resistance syndrome is characterised by an altered relationship between leptin, IGFBP-1 and insulin.
Department of Medicine, Umeå University Hospital, Sweden. stefan.soderberg@medicin.umu.se
S
S
Söderberg
B
B
Ahrén
M
M
Eliasson
B
B
Dinesen
K
K
Brismar
T
T
Olsson
D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology; D000886:Anthropometry; D001786:Blood Glucose / Q000378:metabolism; D003430:Cross-Sectional Studies; D005215:Fasting; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D020738:Leptin / Q000097:blood*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009765:Obesity / Q000097:blood* / Q000378:metabolism; D017698:Postmenopause / Q000097:blood* / Q000378:metabolism; D017697:Premenopause / Q000097:blood / Q000378:metabolism; D011384:Proinsulin / Q000097:blood; D012907:Smoking; D013548:Sweden
D001786:Blood Glucose; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D020738:Leptin; D007334:Insulin-Like Growth Factor I; D011384:Proinsulin