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Prognostic value of circulating vitamin D binding protein, total, free and bioavailable 25-hydroxy vitamin D in patients with colorectal cancer.[Pubmed:28388568]

Oncotarget. 2017 Jun 20;8(25):40214-40221.

Numerous studies have suggested that there was a significantly positive association between circulating total 25-hydroxyvitamin D (25(OH)D) and survival in colorectal cancer patients. Moreover, plasma vitamin D was also found significantly associated with the concentration of vitamin D binding protein (VDBP). However, there was no paper to clarify the prognostic value of VDBP, free and bioavailable 25(OH)D in colorectal carcinogenesis. The aim of this study was to comprehensively assess the prognostic value of VDBP, total, free and bioavailable 25(OH)D in stage I-III colorectal cancer patients. A total of 206 colorectal cancer patients were enrolled in this prospective study. Preoperative plasma total 25(OH)D and VDBP concentrations were measured by direct enzyme-linked immunosorbent assay, and albumin concentration was measured by Beckman automatic biochemical analyzer. Free and bioavailable 25(OH)D concentrations were calculated based on the concentrations of plasma VDBP, total 25(OH) D and albumin. X-title program was used to determine the optimal cut-off values of VDBP, total, free and bioavailable 25(OH)D. Results showed that elevated free and bioavailable 25(OH)D were significantly associated with better 5-year overall survival (OS) by univariate analysis. By multivariate cox analysis, we also found that the high level of free 25(OH)D (HR = 0.442, 95%CI = 0.238-0.819, P < 0.010) could be identified as an independent factor for better OS. In conclusion, our study suggested that higher levels of free and bioavailable 25(OH)D were associated with better OS in stage I-III colorectal cancer patients. Moreover, free 25(OH)D could be considered as an independent prognostic biomarker for OS.

The vitamin D receptor functional variant rs2228570 (C>T) does not associate with type 2 diabetes mellitus.[Pubmed:28388281]

Endocr Res. 2017 Nov;42(4):331-335.

AIM: Vitamin D acts through the binding to the vitamin D receptor (VDR). Several polymorphisms in VDR gene have been studied. Among these, the rs2228570 C>T (FokI) variant has been demonstrated to be functional, leading to a protein with a different size and activity. So far, genetic studies on the association between VDR gene rs2228570 single nucleotide polymorphism (SNP) and type 2 diabetes mellitus (T2DM) showed contradictory results. Thus, we performed an association study in a large cohort of adult Italian subjects with T2DM and in nondiabetic controls. MATERIALS AND METHODS: For this study, 1713 subjects, 883 T2DM patients and 830 controls, were genotyped for the polymorphism. All participants without a diagnosis of diabetes underwent oral glucose tolerance test (OGTT), with measurement of glucose and insulin levels. Indices of insulin resistance (Homeostatic model assessment of insulin resistance, insulin sensitivity index), secretion (homeostatic model assessment for beta-cell, corrected insulin response at 30 minutes) and disposition index were calculated. RESULTS: Genotype distributions and allele frequencies did not show difference between T2DM subjects and controls. We did not find significant differences among the three genotypes regarding gender, age, BMI, waist, hip, waist-to-hip ratio, and blood pressure. There were also no significant differences in lipid parameters, aspartate aminotransferase, and alanine aminotransferase levels. We tested for association with OGTT-derived data and surrogate indices of insulin resistance and secretion. We did not find significant differences among the genotypes in any of above-mentioned parameters. Furthermore, vitamin D levels were measured in a subgroup of subjects. We did not find significant differences among the genotypes. CONCLUSIONS: Our study does not provide evidence for the association of the rs2228570 polymorphism with T2DM in a Caucasian population.

Clinical decision tool for CRT-P vs. CRT-D implantation: Findings from PROSE-ICD.[Pubmed:28388657]

PLoS One. 2017 Apr 7;12(4):e0175205.

BACKGROUND: Cardiac resynchronization therapy (CRT) devices reduce mortality through pacing-induced cardiac resynchronization and implantable cardioverter defibrillator (ICD) therapy for ventricular arrhythmias (VAs). Whether certain factors can predict if patients will benefit more from implantation of CRT pacemakers (CRT-P) or CRT defibrillators (CRT-D) remains unclear. METHODS AND RESULTS: We followed 305 primary prevention CRT-D recipients for the two primary outcomes of HF hospitalization and ICD therapy for VAs. Serum biomarkers, electrocardiographic and clinical variables were collected prior to implant. Multivariable analysis using Cox-proportional hazards model was used to fit the final models. Among 282 patients with follow-up outcome data, 75 (26.6%) were hospitalized for HF and 31 (11%) received appropriate ICD therapy. Independent predictors of HF hospitalization were atrial fibrillation (HR = 1.8 (1.1,2.9)), NYHA class III/IV (HR = 2.2 (1.3,3.6)), ejection fraction <20% (HR = 1.7 (1.1,2.7)), HS-IL6 >4.03pg/ml (HR = 1.7 (1.1,2.9)) and hemoglobin (<12g/dl) (HR = 2.2 (1.3,3.6)). Independent predictors of appropriate therapy included BUN >20mg/dL (HR = 3.0 (1.3,7.1)), HS-CRP >9.42mg/L (HR = 2.3 (1.1,4.7)), no beta blocker therapy (HR = 3.2 (1.4,7.1)) and hematocrit >/=38% (HR = 2.7 (1.03,7.0)). Patients with 0-1 risk factors for appropriate therapy (IR 1 per 100 person-years) and >/=3 risk factors for HF hospitalization (IR 23 per 100-person-years) were more likely to die prior to receiving an appropriate ICD therapy. CONCLUSIONS: Clinical and biomarker data can risk stratify CRT patients for HF progression and VAs. These findings may help characterize subgroups of patients that may benefit more from the use of CRT-P vs. CRT-D systems. TRIAL REGISTRATION: ClinicalTrials.gov NCT00733590.