DENSITA¿ MINERALE OSSEA, QUALITA¿ DELL¿OSSO E RISCHIO DI FRATTURA NEL DIABETE MELLITO TIPO 2:RUOLO DELL¿ASSE IPOTALAMO-IPOFISI-SURRENE EDELLA SENSIBILITA¿ AI GLUCOCORTICOIDI

Introduzione: Nel Diabete Mellito di tipo 2 (T2D) vi \ue8 un aumento del rischio di frattura vertebrale (VFx). L\u2019asse ipotalamo-ipofisi-surrene (HPA) sembra attivato nel T2D scompensato e la sensibilit\ue0 ai glucocorticoidi (GC) sembra influenzare la densit\ue0 minerale ossea (DMO) nei soggetti con osteoporosi. Obiettivo: Valutare il ruolo dell\u2019asse HPA e della sensibilit\ue0 ai GC, mediante i polimorfismi (SNPs) BclI e N363S del recettore GC e l\u2019attivit\ue0 della 11\u3b2idrossisteroidodeidrogenasi tipo 2, (11HSD2) sulla DMO, VFx e qualit\ue0 dell\u2019osso valutata mediante il Trabecular Bone Score, (TBS), in donne con T2D compensato in menopausa. Materiali/metodi: in 92 donne con T2D (emoglobina glicata 6.7\ub11.2%) e 92 controlli, paragonabili per et\ue0, sesso, BMI, abbiamo valutato: 1) metabolismo calcio-fosforo, livelli ACTH, cortisoluria 24h (CLU), cortisone (CoLU) su urine 24h, cortisolo dopo 1 mg desametasone h 23 (1mgDST); 2) attivit\ue0 del 11HSD2 (rapporto CLU/CoLU), SNPs di BclI e N363S; 3) DMO (Z-score, lombare, LS e collo femorale, FN) e TBS (Z-score) mediante DXA e VFx mediante morfometria. Risultati: Le pazienti con T2D hanno mostrato, rispetto ai controlli, VFx aumentate (34.8 vs 19.6 %, rispettivamente, p=0.031) e DMO maggiore (LS 0.81\ub10.47 vs 0.17\ub11.32, p=0.002; FN 0.63\ub10.99 vs 0.04\ub10.94, p=0.000), mentre TBS, attivit\ue0 HPA e 11HSD2, e prevalenza degli SNPs di BclI e N363S sono risultate paragonabili. Le pazienti con T2D e VFx hanno mostrato un\u2019aumentata frequenza dello SNPs N363S in eterozigosi (15.6%) e DMO e TBS minori rispetto a quelle senza VFx (3.3%, p=0.047), ma simili secrezione di cortisolo, attivit\ue0 11HSD2 e frequenza dello SNP BclI. Lo stesso \ue8 risultato nei soggetti di controllo. Le VFx sono risultate associate al T2D (OR=2.6, 95%CI 1.2-5.5, p=0.015) ed allo SNP N363S in eterozigosi (OR=8.5, 95%CI 2.3-31.1, p=0.01). Conclusioni: Nel T2D compensato la prevalenza di VFx \ue8 aumentata e, come nella popolazione generale, sembra associata ad un\u2019aumentata sensibilit\ue0 ai GC.Introduction: Patients affected by type 2 diabetes (T2D) are at increased risk of vertebral fractures (VFx). At the same time, there is evidence of activated hypothalamus-pituitary-adrenal (HPA) axis in T2D, and an increased glucocorticoid (GC) sensitivity seems to have a negative impact on bone mineral density (BMD) in osteoporosis. Objectives: To evaluate the association between HPA axis activity and GC sensitivity, measured by single nucleotide polymorphisms (SNPs) BclI, N363S of GC receptor and by activity of 11HSD2, with BMD, VFx and bone quality, evaluated with Trabecular Bone Score (TBS), in T2D postmenopausal women. Material/methods: We recruited 92 T2D women (HbA1c 6.7\ub11.2%) and 92 age- and BMI-matched controls. The following parameters were evaluated in all subjects: 1) calcium-phosphorus metabolism, ACTH, urine free cortisol 24h (UFC), urine free cortisone 24h (UFCo), serum cortisol after overnight 1 mg dexamethasone (1mgDST); 2) activity of 11HSD2 (ratio UFC/UFCo), SNPs of BclI, N363S; 3) BMD (Z-score, lumbar spine, LS, femoral neck, FN), TBS (Z-score) with DXA and VFx with radiography. Results: T2D subjects had increased prevalence of VFx (34.8 vs 19.6 %, respectively, p=0.031) in presence of increased BMD (LS 0.81\ub10.47 vs 0.17\ub11.32, p=0.002; FN 0.63\ub10.99 vs 0.04\ub10.94, p=0.000), in comparison to controls. There were no differences in TBS, HPA parameters, 11HSD2 activity, prevalence of BclI and N363S SNPs between groups. T2D patients with VFx had reduced levels of FN BMD, TBS and increased prevalence of the N363S SNPs (15.6%), compared to T2D ones without VFx. No differences were found in HPA parameters, 11HSD2 activity, prevalence of the BclI SNPs. The same pattern was seen in controls. In logistic regression analysis VFx were associated with T2D (OR=2.6, 95%CI 1.2-5.5, p=0.015) and N363S SNPs (OR=8.5, 95%CI 2.3-31.1, p=0.01) Conclusions: In subjects with and without T2D the presence of VFx is associated with increased GC sensitivity