In Postmenopausal Female Subjects With Type 2 Diabetes Mellitus, Vertebral Fractures Are Independently Associated With Cortisol Secretion and Sensitivity

CONTEXT: 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. DESIGN AND SETTING: This was a case-control study in an outpatient setting. PATIENTS: 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). MAIN OUTCOME MEASURES: 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.