Biomedical subjects

José-Manuel Fernandez-Real

Publications and source records attributed to José-Manuel Fernandez-Real.

3 recordsLinked to original sources

PubMed2005

Corticosteroid-binding globulin affects the relationship between circulating adiponectin and cortisol in men and women.

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.

Adiponectin↗

PubMed2002

Shedding of TNF-alpha receptors, blood pressure, and insulin sensitivity in type 2 diabetes mellitus.

Tumor necrosis factor-alpha (TNF-alpha) is increasingly recognized as a key component in the development of insulin resistance and increased blood pressure. In a sample of 368 individuals, the ratio of soluble TNF-alpha receptors (sTNFR2/sTNFR1) correlated positively with systolic and diastolic blood pressure (P < 0.01). This ratio was significantly greater in type 2 diabetic subjects (DM-2) than in type 1 diabetic patients and was greater than in control nondiabetic subjects (P < 0.00001). The TNF-alpha receptor 1 (TNFR1) density in peripheral blood monocytes was similar in DM-2 patients and in nondiabetic subjects. After phorbol 12-myristate 13-acetate, TNFR1 shedding was significantly decreased in DM-2 compared with control subjects, and it was directly associated with insulin sensitivity (r = 0.54, P = 0.03). Serum sTNFR1 concentration was also linked to the vasodilatory response to glyceryltrinitrate (P = 0.01). Conversely, TNF-alpha receptor 2 shedding was negatively associated with insulin sensitivity (r = -0.54, P = 0.03), whereas shedding of L-selectin showed no significant association. After exercise-induced lowering of blood pressure, a parallel decrease in sTNFR2/sTNFR1 was observed in DM-2 patients. Our findings suggest that insulin resistance and blood pressure are linked to altered shedding of TNF-alpha receptors in DM-2. The latter seems reversible and is not genetically determined.

Adult↗

PubMed2002

Serum corticosteroid-binding globulin concentration and insulin resistance syndrome: a population study.

It has been suggested that a low grade inflammatory state could predispose for developing insulin resistance and contribute to the development of obesity and type 2 diabetes. Corticosteroid-binding globulin (CBG), the main plasma protein transport for cortisol, has been shown to be negatively regulated by insulin and IL-6, at least in vitro, suggesting that insulin resistance and inflammation may both contribute to decreasing CBG levels. In the present study we measured CBG concentrations in a human healthy population and investigated the relationships of CBG with anthropometric and biochemical markers for inflammation and/or insulin resistance. The data showed that the mean serum CBG level was significantly lower in males (n = 151) than in females (n = 113; 32.5 +/- 9.1 vs. 39.2 +/- 13.9 mg/liter; P < 0.0001). In both sexes serum CBG levels were correlated negatively with age (r = -0.12; P = 0.04), body mass index (r = -0.31; P < 0.0001), waist to hip ratio (WHR; r = -0.39; P < 0.0001), systolic (r = -0.15; P < 0.01) and diastolic (r = -0.15; P = 0.01) blood pressures, and HOMA, an index of insulin resistance (r = -0.12; P = 0.04). In addition, the CBG concentration was negatively associated with serum IL-6 concentrations (r = -0.23; P = 0.017) and with the soluble fraction of TNFalpha receptors, soluble TNF receptor 1 (sTNFR1; r = -0.35; P < 0.0001), and sTNFR2 (r = -0.56; P < 0.0001) in women. A stepwise regression analysis using CBG as an independent variable showed that sex (P < 0.00001), body mass index (P = 0.0002), and HOMA (P = 0.0005), but not systolic blood pressure, diastolic blood pressure, IL-6, sTNFR1, or sTNFR2, constituted significant independent factors that explained 21% of the CBG variance (14%, 2%, and 5%, respectively). In a subsample of 120 men and 68 women, fasting serum free cortisol (calculated as the ratio fasting cortisol/CBG) was significantly associated with WHR (r = 0.24; P = 0.001), systolic (r = 0.18; P = 0.01) and diastolic (r = 0.19; P = 0.007) blood pressures, and HOMA value (r = 0.20; P = 0.005), but not with BMI or age. BMI (P < 0.0001), free cortisol (P = 0.003), and CBG (P = 0.009), but not WHR and age, contributed to 20%, 6%, and 8%, respectively, of HOMA variance in women in a multiple regression analysis. In this model only BMI (P < 0.0001) independently contributed to HOMA variance in men. These findings support the hypothesis that the CBG level is an interesting indicator for both insulin resistance and low grade inflammation. Whether the decrease in CBG levels is genetic by nature or directly associated to increased insulin and/or IL-6 merits further investigation. Nevertheless, because CBG has been shown to be expressed by the adipose tissue, decreased CBG could create locally increased cortisol disposal, with no change in circulating cortisol, and facilitate fat accumulation, insulin resistance, and type 2 diabetes.

Adult↗