Dataset Information

Phase Angle: A Possible Biomarker to Quantify Inflammation in Subjects with Obesity and 25(OH)D Deficiency.

ABSTRACT: Obesity is associated to chronic low-grade metabolic inflammation and hypovitaminosis D. Among extra-skeletal effects, an important role in inflammation has been described for vitamin D (25(OH)D). Phase angle (PhA) is a bioelectrical impedance analysis (BIA) parameter that represents an indicator of cellular health in chronic inflammatory states. However, it is still unknown whether a low 25(OH)D levels might correlate with PhA in obesity. Considering the lack of evidence correlating the 25(OH)D levels with PhA in obesity, the aim of this study was to investigate their possible relationship in a group of patients with obesity stratified according to body mass index (BMI) categories. Four hundred and fifty-five adult subjects (219 males and 236 females; 36 ± 11 years) were enrolled. Body composition, including PhA, was assessed using a BIA phase-sensitive system. Serum levels of 25(OH)D was determined by a direct competitive chemiluminescence immunoassay. Most of the participants were affected by grade III obesity (24%) and had 25(OH)D deficiency (67%). Subjects with 25(OH)D deficiency had highest BMI (p < 0.001). Stratifying the sample population according to the BMI classes, 25(OH)D levels decreased significantly along with the increase in BMI (p < 0.001), with the lowest 25(OH)D levels in the class III obesity. In addition, stratifying the sample population according to 25(OH)D categories, BMI and fat mass (FM) decreased, while PhA increased significantly along with the 25(OH)D categories (p < 0.001). The 25(OH)D levels showed significant positive associations with PhA (r = -0.59, p < 0.001), and this association remained significant also after adjusting for BMI and FM (r = 0.60, p < 0.001). The lowest values of PhA were significantly associated with the severity of obesity (OR 0.3, p < 0.001) and of 25(OH)D deficiency (OR 0.2, p < 0.001). To compare the relative predictive power of body composition parameters associated with the 25(OH)D levels, we performed a multiple linear regression analysis. The most sensitive and specific cut-off for 25(OH)D levels to predict the PhA above the median was >14 ng/mL (p < 0.001). In conclusion, we provided preliminary insights into a novel link between 25(OH)D levels and PhA in the setting of obesity. This association uncovered a new potential usefulness of PhA as expression of cell membrane integrity and predictor of inflammation in low 25(OH)D status that might help in identifying high-risk patients with obesity who could benefit from careful 25(OH)D supplementation.

SUBMITTER: Barrea L

PROVIDER: S-EPMC6723101 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Phase Angle: A Possible Biomarker to Quantify Inflammation in Subjects with Obesity and 25(OH)D Deficiency.

Barrea Luigi L Muscogiuri Giovanna G Laudisio Daniela D Di Somma Carolina C Salzano Ciro C Pugliese Gabriella G de Alteriis Giulia G Colao Annamaria A Savastano Silvia S

Nutrients 20190729 8

Obesity is associated to chronic low-grade metabolic inflammation and hypovitaminosis D. Among extra-skeletal effects, an important role in inflammation has been described for vitamin D (25(OH)D). Phase angle (PhA) is a bioelectrical impedance analysis (BIA) parameter that represents an indicator of cellular health in chronic inflammatory states. However, it is still unknown whether a low 25(OH)D levels might correlate with PhA in obesity. Considering the lack of evidence correlating the 25(OH)D ...[more]

PMID: 31362440

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Project description:RationalePatients with chronic rhinosinusitis with nasal polyps (CRSwNP) have been shown to be vitamin D3 (VD3) deficient, which is associated with more severe disease and increased polyp size. To gain mechanistic insights into these observational studies, we examined the impact of VD3 deficiency on inflammation and VD3 metabolism in an Aspergillus fumigatus (Af) mouse model of chronic rhinosinusitis (Af-CRS).MethodsBalb/c mice were fed control or VD3 deficient diet for 4 weeks. Mice were then sensitized with intraperitoneal Af, and one week later given Af intranasally every three days for four weeks while being maintained on control or VD3 deficient diet. Airway function, sinonasal immune cell infiltrate and sinonasal VD3 metabolism profiles were then examined.ResultsMice with VD3 deficiency had increased Penh and sRaw values as compared to controls as well as exacerbated changes in sRaw when coupled with Af-CRS. As compared to controls, VD3 deficient and Af-CRS mice had reduced sinonasal 1α-hydroxylase and the active VD3 metabolite, 1,25(OH)2D3. Differential analysis of nasal lavage samples showed that VD3 deficiency alone and in combination with Af-CRS profoundly upregulated eosinophil, neutrophil and lymphocyte numbers. VD3 deficiency exacerbated increases in monocyte-derived dendritic cell (DC) associated with Af-CRS. Conversely, T-regulatory cells were decreased in both Af-CRS mice and VD3 deficient mice, though coupling VD3 deficiency with Af-CRS did not exacerbate CD4 or T-regulatory cells numbers. Lastly, VD3 deficiency had a modifying or exacerbating impact on nasal lavage levels of IFN-γ, IL-6, IL-10 and TNF-α, but had no impact on IL-17A.ConclusionsVD3 deficiency causes changes in sinonasal immunity, which in many ways mirrors the changes observed in Af-CRS mice, while selectively exacerbating inflammation. Furthermore, both VD3 deficiency and Af-CRS were associated with altered sinonasal VD3 metabolism causing reductions in local levels of the active VD3 metabolite, 1,25(OH)2D3, even with adequate circulating levels.

Project description:STUDY QUESTION:Is pre-conception 25(OH)D associated with the per cycle probability of conception, i.e fecundability, in a prospective cohort study? SUMMARY ANSWER:There are suggestive associations of high 25(OH)D (at least 50 ng/ml) with increased fecundability and low 25(OH)D (<20 ng/ml) with reduced fecundability, but the estimates were imprecise. WHAT IS KNOWN ALREADY:Vitamin D has been associated with reproductive function and fertility in animal studies, but few human studies exist. STUDY DESIGN, SIZE, DURATION:This community-based prospective cohort study included 522 women attempting to become pregnant between 2010 and 2016. The women completed online daily and monthly diaries until a positive home pregnancy test was observed or 12 months had elapsed. PARTICIPANTS/MATERIALS, SETTING, METHODS:The study included women from central North Carolina who were aged 30-44 with no history of infertility, with no more than 3 months of attempt time at recruitment. Women recorded vaginal bleeding so that the ongoing number of attempt cycles could be counted and used to quantify a woman's pregnancy attempt time. Blood collected at the study entry was analysed for 25(OH)D using liquid chromatography tandem mass spectrometry. Associations with fecundability were estimated with a log-binomial discrete time-to-event model. MAIN RESULTS AND THE ROLE OF CHANCE:Among 522 women, 257 conceived during the study. The mean age was 33 years and the mean 25(OH)D was 36 ng/ml. There was an estimated 10% higher fecundability with each 10 ng/ml increase in 25(OH)D (fecundability ratio (FR) 1.10, 95% CI: 0.96, 1.25). The suggestive dose-response association with the continuous measure of 25(OH)D was driven by women in the lowest and the highest categories of 25(OH)D. Compared to women with 25(OH)D of 30-40 ng/ml, women below 20 ng/ml had an estimated 45% reduction in fecundability (FR (CI): 0.55 (0.23, 1.32)), and women with at least 50 ng/ml had an estimated 35% increase in fecundability (FR (CI): 1.35 (0.95, 1.91)). Across these three categories (25(OH)D of <20 ng/ml, 30-40 ng/ml and?>?50 ng/ml), the probability of taking longer than 6 months to conceive was, respectively, 51% (17%, 74%), 28% (17%, 39%) and 15% (10%, 37%). LIMITATIONS, REASONS FOR CAUTION:While the distribution of 25(OH)D was wide, the number of observed cycles with high 25(OH)D (N?=?107) or low 25(OH)D (N?=?56) was small. WIDER IMPLICATIONS OF THE FINDINGS:Our findings are consistent with prior reports of reduced fertility in women with 25(OH)D concentrations below the clinically defined deficiency level (20 ng/ml). Further studies are needed to evaluate the possible reproductive benefits of considerably higher 25(OH)D concentration (>50 ng/ml). STUDY FUNDING/COMPETING INTEREST(S):This research was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health (NIH) under award numbers R00HD079659 and R01HD067683 and supported in part by the Intramural Research Program of the National Institute of Environmental Health Sciences, under projects ES103086, ES049003 and ES044003. ClearBlue ovulation predictor kits were generously donated to AMZJ and AJW by Swiss Precision Diagnostics. Drs Wilcox and Jukic report non-financial support from Swiss Precision Diagnostics during the conduct of the study; Dr Jukic reports non-financial support from Theralogix, LLC, outside the submitted work. Otherwise there are no competing interests. TRIAL REGISTRATION NUMBER:N/A.

Project description:ContextThe optimal measure of vitamin D status is unknown.ObjectiveTo directly measure circulating free 25-hydroxyvitamin D [25(OH)D] concentrations and relationships to total 25(OH)D in a clinically diverse sample of humans.DesignCross-sectional analysis.SettingSeven academic sites.PatientsA total of 1661 adults: healthy (n = 279), prediabetic (n = 479), outpatients (n = 714), cirrhotic (n = 90), pregnant (n = 20), nursing home resident (n = 79).InterventionsMerge research data on circulating free 25(OH)D (directly-measured immunoassay), total 25(OH)D (liquid chromatography/tandem mass spectrometry), D-binding protein [DBP; by radial (polyclonal) immunodiffusion assay], albumin, creatinine, intact parathyroid hormone, and DBP haplotype.Main outcome measuresDistribution of free 25(OH)D (ANOVA with Bonferroni correction for post hoc comparisons) and relationships between free and total 25(OH)D (mixed-effects modeling incorporating clinical condition, DBP haplotype with sex, race, estimated glomerular filtration rate (eGFR), body mass index (BMI), and other covariates).ResultsFree 25(OH)D was 4.7 ± 1.8 pg/mL (mean ± SD) in healthy persons and 4.3 ± 1.9 pg/mL in outpatients, with levels of 0.5 to 8.1 pg/mL and 0.9 to 8.1 pg/mL encompassing 95% of healthy persons and outpatients, respectively. Free 25(OH)D was higher in patients with cirrhosis (7.1 ± 3.0 pg/mL; P < 0.0033) and nursing home residents (7.9 ± 2.1 pg/mL; P < 0.0033) than in other groups and differed between whites and blacks (P < 0.0033) and between DBP haplotypes (P < 0.0001). Mixed-effects modeling of relationships between free and total 25(OH)D identified clinical conditions (patients with cirrhosis > nursing home residents > patients with prediabetes > outpatients > pregnant women) and BMI (lesser effect) as covariates affecting relationships but not eGFR, sex, race, or DBP haplotype.ConclusionsTotal 25(OH)D, health condition, race, and DBP haplotype affected free 25(OH)D, but only health conditions and BMI affected relationships between total and free 25(OH)D. Clinical importance of free 25(OH)D needs to be established in studies assessing outcomes.

Dataset Information

Phase Angle: A Possible Biomarker to Quantify Inflammation in Subjects with Obesity and 25(OH)D Deficiency.

Publications

Phase Angle: A Possible Biomarker to Quantify Inflammation in Subjects with Obesity and 25(OH)D Deficiency.

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