The association between leptin and proinsulin is lost with central obesity.
OBJECTIVE
Hyperproinsulinaemia and hyperleptinaemia are interrelated features of the insulin resistance syndrome that are linked to the prospective risk of cardiovascular diseases. Whether the association between leptin and proinsulin is different between groups displaying different degrees of risk for cardiovascular diseases is not known. We therefore examined this association in men versus women and in pre- versus postmenopausal women from a population-based sample.


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


METHODS
Anthropometric measurements (body mass index and waist circumference) and oral glucose tolerance tests were performed. Enzyme-linked immunosorbent assays were used for the analyses of specific insulin and proinsulin, and radioimmunoassay for leptin. Insulin resistance and beta-cell function were calculated according to the homeostasis assessment model. Partial correlation coefficients adjusted for age and measures of adiposity were calculated and multiple linear regression analyses were performed with leptin as dependent variable.


RESULTS
In nonobese men and premenopausal women and in obese postmenopausal women, leptin was significantly associated with proinsulin after stratification for waist circumference. Furthermore, a multivariate analyses taking age and measures of adiposity into account, showed that high fasting proinsulin was a significant predictor of high leptin in these groups. In contrast, this association was lost with increasing central obesity in men and premenopausal women.


CONCLUSIONS
This study shows that both the degree of adiposity and the hormonal milieu influence the association between circulating leptin and proinsulin in a normal population. Therefore, the insulin resistance syndrome seems to be characterized by lost association between leptin and proinsulin, which may be explained by dysfunction in the adipoinsular axis.
Söderberg
S
S
Department of Medicine, Umeå University, Umeå, Sweden. stefan.soderberg@medicine.umu.se
Ahrén
B
B
Eliasson
M
M
Dinesen
B
B
Olsson
T
T
D000005:Abdomen; D000273:Adipose Tissue; D000328:Adult; D000367:Age Factors; D000368:Aged; D001824:Body Constitution; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D020738:Leptin / Q000097:blood*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood* / Q000453:epidemiology / Q000473:pathology; D011237:Predictive Value of Tests; D011384:Proinsulin / Q000097:blood*; D013548:Sweden / Q000453:epidemiology
D020738:Leptin; D011384:Proinsulin