title: Increased urinary glucocorticoid metabolites are associated with metabolic syndrome, hypoadiponectinemia, insulin resistance and β cell dysfunction.
abstract: Metabolic syndrome (MetS) may have increased cortisol (F) production caused by 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) in liver and adipose tissue and/or by HPA axis dysregulation. F is then mainly metabolized by liver reductases into inactive tetrahydrometabolites (THMs). We measured THM levels in patients with or without MetS and evaluate the correlation between THMs and anthropometric and biochemical parameters. We recruited 221 subjects, of whom 130 had MetS by ATP III. We evaluated F, cortisone (E), adipokines, glucose, insulin and lipid profiles as well as urinary (24h) F, E and THM levels. β Cell function was estimated by the HOMA Calculator. We observed that patients with MetS showed higher levels of THMs, HOMA-IR and leptin and lower levels of adiponectin and HOMA-β but no differences in F and E in plasma or urine. THM was associated with weight (r = +0.44, p<0.001), waist circumference (r = +0.38, p<0.01), glycemia (r = +0.37, p<0.01), and triglycerides (r = +0.18, p=0.06) and negatively correlated with adiponectin (r = -0.36, p<0.001), HOMA-β (r = -0.21, p<0.001) and HDL (r = -0.29, p<0.01). In a logistic regression model, THM levels were associated with hypertension, hyperglycemia and dyslipidemia. We conclude that MetS is associated with increased urinary THMs but not with F and E levels in plasma or urine. Increased levels of THM, reflecting the daily cortisol production subsequently metabolized, are correlated with hypoadiponectinemia, hypertension, dyslipidemia, insulin resistance and β cell dysfunction. A subtle increased in glucocorticoid production may further account for the phenotypic and biochemical similarities observed in central obesity and Cushing's syndrome.
authors: Department of Endocrinology, School of Medicine, Pontificia Universidad Católica de Chile, Chile.
authors: Rene
authors: R
authors: Baudrand
authors: Carmen
authors: C
authors: Campino
authors: Cristian A
authors: CA
authors: Carvajal
authors: Oliviero
authors: O
authors: Olivieri
authors: Giancesare
authors: G
authors: Guidi
authors: Giovanni
authors: G
authors: Faccini
authors: Javiera
authors: J
authors: Sateler
authors: Javiera
authors: J
authors: Cornejo
authors: Betty San
authors: BS
authors: Martin
authors: Jose M
authors: JM
authors: Dominguez
authors: Jaime
authors: J
authors: Cerda
authors: Lorena M
authors: LM
authors: Mosso
authors: Gareth I
authors: GI
authors: Owen
authors: Alexis M
authors: AM
authors: Kalergis
authors: Carlos E
authors: CE
authors: Fardella
mesh_terms: D052242:Adiponectin / Q000378:metabolism*; D000328:Adult; D005260:Female; D005938:Glucocorticoids / Q000378:metabolism* / Q000652:urine*; D006801:Humans; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology*; D050356:Lipid Metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism* / Q000652:urine; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism / Q000652:urine
chemical_list: D052242:Adiponectin; D005938:Glucocorticoids