RESUMEN
OBJECTIVE: This cross-sectional study was undertaken to assess metabolic bone disease by examining bone mineral density (BMD), fracture prevalence, and nutritional factors pertinent to bone in a cohort >9 years post-Rouxen-Y gastric bypass (RYGB). METHODS: Fifty-one subjects 9.4 to 36.0 years (mean 17.0 ± 8.1) post-RYGB provided a focused history. Dietary calcium and protein were assessed. Dual-energy X-ray absorptiometry (DXA) BMD at the spine, hip, and radius and routine serum chemistries, magnesium, phosphorus, parathyroid hormone, vitamin D, vitamin K, and micronutrients were analyzed. Sixteen subjects provided 24-hour urine for measurement of calcium. RESULTS: The mean maximum weight loss was 70.3 ± 20 kg (47.4 ± 8.9%), and mean net weight loss was 46.9 ± 23.1 kg (31.2 ± 12.5%). The prevalence rates of fracture, secondary hyperparathyroidism, and vitamin D deficiency were 15.7%, 37%, and 39%, respectively. BMD was in the osteoporotic range in 27.5%. The mean calcium:creatinine clearance ratio was 0.0124 ± 0.0131. Median intakes of dietary calcium, total calcium, protein, and vitamin D were 582.5 mg, 947.5 mg, 50.2 g, and 1,000 IU, respectively. Mean Z-scores at all sites were <0 (P<.01). A negative correlation (P<.05) was noted between distal radius Z-score and net change in BMI. Net change in BMI was greater for those with osteoporosis than those without. (P<.05) Conclusion: Many years after RYGB, BMD remains lower than expected compared to an age-, sex-, race-, and weight-matched reference population and is correlated with the amount of weight lost. Deficiencies of Vitamin D and calcium are prevalent. ABBREVIATIONS: BMD = bone mineral density BMI = body mass index Ca:Cr = calcium:creatinine DXA = dual-energy X-ray absorptiometry PTH = parathyroid hormone RYGB = Roux-en-Y gastric bypass UD = ultradistal WHO = World Health Organization.
Asunto(s)
Densidad Ósea , Derivación Gástrica/efectos adversos , Adulto , Anciano , Índice de Masa Corporal , Estudios Transversales , Femenino , Humanos , Hiperparatiroidismo Secundario/etiología , Masculino , Persona de Mediana Edad , Osteoporosis/etiología , Proyectos PilotoAsunto(s)
Adenoma/diagnóstico , Cefalea/diagnóstico , Hipotensión Intracraneal/diagnóstico , Neoplasias Hipofisarias/diagnóstico , Adenoma/patología , Diagnóstico Diferencial , Femenino , Cefalea/patología , Humanos , Hipotensión Intracraneal/patología , Imagen por Resonancia Magnética/métodos , Persona de Mediana Edad , Neoplasias Hipofisarias/patologíaRESUMEN
Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF), the critical molecule in tumor angiogenesis, is regulated by different stimuli, such as hypoxia and oncogenes, and also by growth factors. Previously we have shown that in AsPC-1 pancreatic adenocarcinoma cells, insulin-like growth factor receptor (IGF-IR) regulates VPF/VEGF expression. Insulin receptor substrate-1 and -2 (IRS-1 and IRS-2), two major downstream molecules of IGF-1R, are known to be important in the genesis of diabetes. In this study, we have defined a new role of IRS in angiogenesis. Both of the IRS proteins modulate VPF/VEGF expression in pancreatic cancer cells by different mechanistic pathways. The Sp1-dependent VPF/VEGF transcription is regulated mainly by IRS-2. Protein kinase C-zeta (PKC-zeta) plays a central role in VPF/VEGF expression and acts as a switching element. Furthermore, we have also demonstrated that the phosphatidylinositol 3-kinase pathway, but not the Ras pathway, is a downstream event of IRS proteins for VPF/VEGF expression in AsPC-1 cells. Interestingly, like renal cancer cells, in AsPC-1 cells PKC-zeta leads to direct Sp1-dependent VPF/VEGF transcription; in addition, it also promotes a negative feedback loop to IRS-2 that decreases the association of IRS-2/IGF-1R and IRS-2/p85. Taken together, our results show that in AsPC-1 pancreatic carcinoma cells, Sp1-dependent VPF/VEGF transcription is controlled by IGF-1R signaling through IRS-2 proteins and modulated by a negative feedback loop of PKC-zeta to IRS-2. Our data also suggest that IRS proteins, which are known to play crucial roles in IGF-1R signaling, are also important mediators for tumor angiogenesis.