Inflammatory pathways are increasingly recognized to be tightly associated with
insulin resistance in humans. The promoter region of the
adiponectin gene--Apm1--encompasses consensus sequences for glucocorticosteroid receptor responsive
element.
Dexamethasone induced downregulation of
adiponectin secretion in vitro, whereas
prednisolone administration increased circulating
adiponectin concentrations. As previous studies have demonstrated an inverse relationship between
corticosteroid-binding globulin (
CBG), body mass index, and
insulin resistance, we studied whether
CBG could explain
cortisol-to-
adiponectin relationship. One hundred twenty-two healthy subjects were enrolled in a cross-sectional study. Plasma
CBG and serum
cortisol concentration were measured by radioimmunoassay. The
cortisol-to-
CBG ratio was used to calculate free
cortisol. An RIA kit (Linco Research, St Louis, MO) was used to measure
adiponectin levels.
Insulin resistance was calculated using the homeostatis model of assessment (HOMA) value. Circulating
adiponectin was associated with serum
CBG ( r = 0.38, P < .00001), both in men ( r = 0.26, P = .03, n = 79) and women ( r = 0.48, P = .003, n = 43), and with
insulin resistance (HOMA index) ( r = -0.30, P < .0001) in both. Free
cortisol correlated negatively with
adiponectin only in women ( r = -0.32, P = .04), but not in men ( r = 0.01, P = .89). Serum
CBG concentration was significantly lower among men in the lowest quartile of
adiponectin when compared with the remaining subjects (37.3 +/- 5.7 vs 40.6 +/- 5.1, P = .016), whereas men in the highest quartile of
adiponectin showed significantly increased free
cortisol index (14.2 +/- 3.3 vs 12.2 +/- 3.1, P = .039). Women in the lowest quartile of
adiponectin also displayed significantly lower
CBG concentration than that present in the remaining subjects (38.6 +/- 6.9 vs 44.4 +/- 5.5, P = .016), whereas free
cortisol index was not significantly different across
adiponectin quartiles ( P = .1). In a stepwise regression analysis, body mass index ( P = .0011),
CBG ( P = .0047), and sex ( P = .04) contributed to 15%, 8%, and 3%, respectively, of
adiponectin variance. Using
CBG as dependent variable, both
adiponectin ( P = .0002) and fasting
cortisol ( P = .019) contributed to 14% and 4%, respectively, of
CBG variance. In summary, circulating
adiponectin,
CBG concentration, and fasting
cortisol were significantly interrelated in healthy subjects. A significant sexual dimorphism exists in this association.