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The Relationship of 25(OH)D₃ with Diabetes Mellitus and the Mediation Effect of Lipid Profile in Chinese Rural Population of Henan Province.

ABSTRACT: Background and Objectives: Studies suggest that vitamin D is involved in the development of type 2 diabetes mellitus (T2DM) and influences serum lipids levels, while lipid disorders are also closely related to T2DM. This study attempts to explore the complex relationship of serum 25(OH)D₃, serum lipids, and T2DM among Chinese population. Materials and Methods: A cross-sectional study was carried out among 2326 subjects. The chi-square (χ²) test was applied to compare the prevalence of T2DM or dyslipidemia between two serum 25(OH)D₃ levels. Linear regression was applied to analyze the correlation between serum lipids and 25(OH)D₃ contents. Univariate and logistic analysis were used to explore the relationship between two lipid levels and T2DM. Mediation analysis was used to explore whether serum lipids mediate the relationship between two serum 25(OH)D₃ levels and T2DM. Results: Compared to subjects with 25(OH)D₃ ≥ 30 ng/mL, subjects with 25(OH)D₃ < 30 ng/mL were higher in the prevalence of T2DM. The occurrences of high TG and low HDL-C were significantly higher in vitamin D deficiency and insufficiency than those in vitamin D sufficiency. Serum 25(OH)D₃ content showed a reverse correlation with TC, TG, and LDL-C, but positive correlation with HDL-C. The odds ratios (ORs) (95% confidence intervals, 95%CI) of T2DM by comparing TG ≥ 2.26 mmol/L vs. TG < 2.26 mmol/L and HDL-C < 1.04 mmol/L vs. HDL-C ≥ 1.04 mmol/L in all participants were 2.48 (1.94-3.18) and 1.37 (1.07-1.75), respectively. Serum TG or HDL-C level partially mediated the relationship between two 25(OH)D₃ level and T2DM. Conclusions: Serum 25(OH)D₃ < 30 ng/mL seems to be associated with T2DM or dyslipidemia (high TG and low HDL-C) in our study, but there is still no proof of a cause-effect relationship. Moreover, serum TG or HDL-C level partially mediated the relationship between 25(OH)D₃ levels and T2DM.

SUBMITTER: Zhang M

PROVIDER: S-EPMC8781849 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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:ContextThere is uncertainty over the equivalence of vitamins D2 and D3 to maintain plasma 25-hydroxyvitamin D (25(OH)D).ObjectiveThe objective of the study was to compare the plasma half-lives of 25(OH)D2 and 25(OH)D3 in two distinct populations with different dietary calcium intake and 25(OH)D status.ParticipantsHealthy men (aged 24 and 39 y), resident in The Gambia (n = 18) or the United Kingdom (n = 18) participated in the study.InterventionsThe intervention included an oral tracer dose of deuterated-25(OH)D2 and deuterated-25(OH)D3 (both 40 nmol). Blood samples were collected over 33 days.Main outcome measures25(OH)D2 and 25(OH)D3 plasma half-lives, concentrations of 25(OH)D, and vitamin D binding protein (DBP) and DBP genotypes were measured.Results25(OH)D2 half-life [mean (SD)] [13.9 (2.6) d] was shorter than 25(OH)D3 half-life [15.1 (3.1) d; P = .001] for countries combined, and in Gambians [12.8 (2.3) d vs 14.7 (3.5) d; P < .001], but not in the United Kingdom [15.1 (2.4) d vs 15.6 (2.5) d; P = .3]. 25(OH)D concentration was 69 (13) and 29 (11) nmol/L (P < .0001), and the DBP concentration was 259 (33) and 269 (23) mg/L (P = .4) in The Gambia and United Kingdom, respectively. Half-lives were positively associated with plasma DBP concentration for countries combined [25(OH)D2 half-life: regression coefficient (SE) 0.03 (0.01) d per 1 mg/L DBP, P = .03; 25(OH)D3 half-life: 0.04 (0.02) d, P = .02] and in Gambians [25(OH)D2 half-life: 0.04 (0.01) d; P = .02; 25(OH)D3 half-life: 0.06 (0.02) d, P = .01] but not in UK participants. The DBP concentration × country interactions were not significant. DBP Gc1f/1f homozygotes had shorter 25(OH)D2 half-lives compared with other combined genotypes (P = .007) after correction for country.Conclusions25(OH)D2 half-life was shorter than 25(OH)D3 half-life, and half-lives were affected by DBP concentration and genotype. The stable isotope 25(OH)D half-life measurements provide a novel tool to investigate vitamin D metabolism and vitamin D expenditure and aid in the assessment of vitamin D requirements.

Project description:Osteoporosis (OP) is a chronic disease in the elderly, and China is entering an aging demographic trend. In recent years, increasing evidence has demonstrated that probiotics can treat osteoporosis. This study aimed to explore the relevant mechanisms and to validate the beneficial effect on osteoporosis by high-throughput metagenome-wide gene sequencing in humans. In this study, compared with controls, several species had altered abundances, and specific functional pathways were found in the OP group. At the species level, the species that had increased in OP individuals were positively correlated to bone resorption markers and negatively correlated to 25-OH-D3 and bone formation markers, with Streptococcus sanguinis showing the strongest relevance, followed by Streptococcus gordonii, Actinomyces odontolyticus, and Olsenella unclassified. Additionally, Actinomyces graevenitzii, enriched in the OP group, was positively correlated to inflammation indicators that included white blood cell (WBC), neutrophil count (NEC), and the neutrophil-to-lymphocyte ratio (NLR) (p < 0.05). Conversely, the levels of Akkermansia muciniphila, Bacteroides eggerthii, Bacteroides fragilis, Bacteroides uniformis, and Butyricimonas synergistic were increased in the control group, which had a negative correlation with bone resorption markers and positive correlation with bone formation markers and 25-OH-D3. Additionally, Bacteroides fragilis had a negative correlation with inflammation indicators (WBC, NEC, and NLR) and the above pathways (p < 0.05). Functional prediction revealed that 106 metabolic pathways, enriched in the OP group, were significantly higher than in the control group (p < 0.05). In particular, pathways related to LPS biosynthesis, phytate degradation, lactate acid, and ethanol fermentation were more abundant in the OP group than in the control and were positively related to WBC and NEC. Taken together, several species with altered abundances and specific functional pathways were found in OP individuals. The role of phytases in OP provides novel epidemiological evidence to elucidate the underlying microbiota-relevant mechanisms in bone mineralization and should be explored further.

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The Relationship of 25(OH)D₃ with Diabetes Mellitus and the Mediation Effect of Lipid Profile in Chinese Rural Population of Henan Province.

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The Relationship of 25(OH)D3 with Diabetes Mellitus and the Mediation Effect of Lipid Profile in Chinese Rural Population of Henan Province.

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OmicsDI is part of the ELIXIR infrastructure

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The Relationship of 25(OH)D₃ with Diabetes Mellitus and the Mediation Effect of Lipid Profile in Chinese Rural Population of Henan Province.