Association between serum 25-hydroxyvitamin D and fasting blood glucose in osteoporosis patients

Osteoporosis (OP) is often associated with other complications, such as impaired glucose homeostasis. Vitamin D deficiency is common and has been linked to bone metabolism and the regulation of blood sugar levels. The aim of this study was to evaluate the independent relationship between serum 25-hydroxyvitamin D (25[OH]D) and fasting blood glucose levels (FBG) in a group of patients diagnosed with OP. This is a retrospective cross-sectional study from a prospectively collected database at our tertiary referral center. Consecutive 2084 OP patients who were hospitalization were finally analyzed in this study. FBG is the dependent variable, serum 25(OH)D level of OP patients is exposure variable of this study. There was a linear significantly negative association between serum 25(OH)D and FBG (β, − 0.02; 95% CI − 0.03 to − 0.01; P = 0.0011) in the fully adjusted models. Specifically, when serum 25(OH)D level was less than 23.39 ng/mL, FBG decreased by 0.04 mmol/L for every 1 ng/mL increase of serum 25(OH)D level. When serum 25(OH)D was greater than 23.39 ng/ mL, the negative association was insignificant (P = 0.9616). If the association is confirmed, the clinical management of blood glucose in OP patients with serum 25(OH)D deficiency has instructive implications.

In the original text, the variable "vitamin D supplementation" was added to We propose the following modification to the methods section: A total of 2409 consecutive patients with newly diagnosed OP and who were hospitalized were included in the study.
And we have reconfigured the legend for the inclusion and exclusion criteria, as illustrated below: Consecutive newly osteoporosis patients during hospitalization (January 2015-March 2022) N=2409

Analyzable cases N=2084
Exclusion (N=325) 1.Age < 50 year (N=73) 2.Patients who fasted for less than 8 hours to undergo fasting blood glucose (FBG) testing (N=54) 3.Patients suffering from medical conditions or taking medications that interfere with glucose metabolism (N=125) 4.Patients with incomplete data (N=73) We have added the following paragraph to address this concern in discussion: It should be noted that our study included patients with various comorbidities, including those affecting bone metabolism and blood sugar levels.While we adjusted for these conditions using the CCI, there may still be residual confounding factors that could influence the observed associations.Additionally, the presence of specific comorbidities, such as Cushing's disease or acromegaly, may have distinct effects on bone metabolism and blood sugar levels, which were not specifically addressed in this study.Future research with a more targeted approach to these specific comorbidities is warranted to further elucidate their impact on the relationship between vitamin D levels and fasting blood glucose.
We have added this information to the section on covariates, as follows:
We have added the following description below the table 1: P-value: ANOVA P-value*: Kruskal-Wallis Rank Test for continuous variables, Fisher Exact for categorical variables with

Expected<10
We have added the following description in statistics:

P-value carried out with ANOVA, P-value* carried out with Kruskal-Wallis Rank Test for continuous variables or Fisher Exact for categorical variables with Expected<10.
We have added the following content in the discussion section (regarding the role of vitamin D in regulating fast blood glucose): D both enhances and promotes insulin secretion from pancreatic β-cells insulin.One of the underlying molecular mechanisms involves the regulation of intracellular Ca2+ concentrations.Nongenomic actions of 1, 25-hydroxyvitamin D3 (1,25[OH]2D3) have been identified as responsible for increasing cytoplasmic Ca2+ levels, leading to activation of insulin exocytosis in pancreatic β-cells and subsequent increased insulin secretion26,27.Vitamin D deficiency can contribute to insulin resistance through several potential mechanisms.For example, the activation of peroxisome proliferator-activated receptor delta (PPAR-δ) by 1,25(OH)2D3 enhances insulin sensitivity28.Additionally, vitamin D improves glucose metabolism by upregulating the Sirtuin 1 (SIRT1)/ insulin receptor substrate1 (IRS1)/ Glucose transporter type 4 (GLUT-4)signaling cascade and enhancing glucose uptake, which is especially evident in high glucose-treated C2C12 mouse myoblast cell (C2C12) myotubes29.Vitamin D also modulates the low-grade chronic inflammation often associated with insulin resistance.Notably, pro-inflammatory cytokines such as Tumor Necrosis Factor-alpha (TNF-α) interfere with peripheral insulin sensitivity by inhibiting insulin-dependent tyrosine phosphorylation of IRS-1.This disrupts the appropriate activation of downstream insulin signaling molecules, including Phosphatidylinositol 3kinase (PI3K), and the translocation of GLUT-4 to the cell surface30,31.Vitamin D counteracts the release of pro-inflammatory cytokines, such as TNF-α and interleukin 6 (IL-6), and C-reactive protein32.Furthermore, the bioactive form of vitamin D strongly suppresses the activation of the nuclear factor kappa-B (NF-κB) and Mitogen-Activated Protein Kinase (MAPK) signaling pathways, effectively preventing the transcription of pro-inflammatory genes33.Consequently, vitamin D significantly alleviates inflammation within adipose tissue.
Table 1, as presented below: a Adjusted for sex, age, BMI, neutrophil count, hemoglobin, albumin, lymphocyte count, high density lipoprotien, category of diagnosis, supplementing vitamin D categorical, season of blood collection, year of blood collection and ICC.