title: In postmenopausal female subjects with type 2 diabetes mellitus, vertebral fractures are independently associated with cortisol secretion and sensitivity.
abstract: BACKGROUND
  In type 2 diabetes (T2D), the vertebral fracture (VFx) prevalence and cortisol secretion are increased.
  
  
  OBJECTIVE
  The objective of this study was to evaluate the role of glucocorticoid secretion and sensitivity in T2D-related osteoporosis.
  
  
  METHODS
  This was a case-control study in an outpatient setting.
  
  
  METHODS
  The patients were ninety-nine well-compensated T2D postmenopausal women (age, 65.7 ± 7.3 y) and 107 controls (age, 64.5 ± 8.2 y).
  
  
  METHODS
  We assessed osteocalcin, C-terminal telopeptide of type I collagen, ACTH, cortisol after the dexamethasone suppression test (F-1mgDST), BclI and N363S single-nucleotide polymorphisms (SNPs) of glucocorticoid receptor, lumbar spine and femoral neck bone mineral density by dual x-ray absorptiometry, and VFx by radiography.
  
  
  RESULTS
  Compared with controls, T2D subjects had increased VFx prevalence (20 vs 34.3%, respectively; P = .031), bone mineral density (Z-scores, lumbar spine, 0.16 ± 1.28 vs 0.78 ± 1.43, P = .001; femoral neck, -0.03 ± 0.87 vs 0.32 ± 0.98, P = .008, respectively), and F-1mgDST (1.06 ± 0.42 vs 1.21 ± 0.44 μg/dL, 29.2 ± 1.2 vs 33.3 ± 1.2 nmol/L, respectively; P = .01), and decreased osteocalcin (10.6 ± 6.4 vs 4.9 ± 3.2 ng/mL, 10.6 ± 6.4 vs 4.9 ± 3.2 μg/L, respectively; P < .0001) and C-terminal telopeptide of type I collagen (0.28 ± 0.12 vs 0.14 ± 0.08 ng/mL, 0.28 ± 0.12 vs 0.14 ± 0.08 mcg/L, respectively; P < .0001). Fractured controls or T2D patients had increased sensitizing N363S SNP prevalence (20 and 17.6%, respectively) compared to non-fractured subjects (3.4 and 3.1%, respectively; P = .02 for both comparisons), and similar BclI SNP prevalence. The VFx presence was associated with the sensitizing variant of N363S SNPs in controls (odds ratio [OR] = 10.6; 95% confidence interval [CI], 1.8-63.3; P = .01) and in T2D patients (OR = 12.5; 95% CI, 1.8-88.7; P = .01), and with the F-1mgDST levels (OR = 2.1; 95% CI, 1.1-4.1; P = .03) only in T2D patients.
  
  
  CONCLUSIONS
  In postmenopausal T2D women, VFx are associated with cortisol secretion and the sensitizing variant of N363S SNPs.
authors.affiliation: Units of Endocrinology and Metabolic Diseases (V.V.Z., C.E.V., E.C., S.P., V.M., E.O., B.M., A.M.B., A.S., I.C.), Nuclear Medicine (F.M.U.), and Epidemiology (E.P., S.F.), Istituto di Ricovero e Cura a Carattere Scientifico, Fondazione Ca' Granda-Ospedale Maggiore Policlinico, 20122 Milan, Italy; Department of Clinical Sciences and Community Health (V.V.Z., E.C., S.P., V.M., A.M.B., S.F., A.S.), University of Milan, 20122 Milan, Italy; and Department of Medical and Pediatric Sciences (A.G., C.E.F.), University of Catania, 95124 Catania, Italy.
authors.forename: Volha V
authors.initials: VV
authors.lastname: Zhukouskaya
authors.forename: Cristina
authors.initials: C
authors.lastname: Eller-Vainicher
authors.forename: Agostino
authors.initials: A
authors.lastname: Gaudio
authors.forename: Elisa
authors.initials: E
authors.lastname: Cairoli
authors.forename: Fabio Massimo
authors.initials: FM
authors.lastname: Ulivieri
authors.forename: Serena
authors.initials: S
authors.lastname: Palmieri
authors.forename: Valentina
authors.initials: V
authors.lastname: Morelli
authors.forename: Emanuela
authors.initials: E
authors.lastname: Orsi
authors.forename: Benedetta
authors.initials: B
authors.lastname: Masserini
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Barbieri
authors.forename: Elisa
authors.initials: E
authors.lastname: Polledri
authors.forename: Silvia
authors.initials: S
authors.lastname: Fustinoni
authors.forename: Anna
authors.initials: A
authors.lastname: Spada
authors.forename: Carmelo Erio
authors.initials: CE
authors.lastname: Fiore
authors.forename: Iacopo
authors.initials: I
authors.lastname: Chiodini
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005787:Gene Frequency; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging; D008661:Metabolism, Inborn Errors / Q000453:epidemiology* / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause / Q000378:metabolism; D015995:Prevalence; D011859:Radiography; D011965:Receptors, Glucocorticoid / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D016103:Spinal Fractures / Q000453:epidemiology* / Q000235:genetics / Q000378:metabolism
chemical_list: D011965:Receptors, Glucocorticoid; D006854:Hydrocortisone