This retrospective study analyzed data from 2,495 hospitalized patients with type 2 diabetes mellitus (T2DM) at the Endocrinology Department of the Second Affiliated Hospital of Fujian Medical University between January 2018 and July 2024. Among the participants, 650 had sufficient vitamin D levels (≥30 ng/mL), 1,006 showed insufficient levels (20-29.9 ng/mL), and 839 were deficient (<20 ng/mL). Inclusion criteria required a T2DM diagnosis according to the Chinese Guidelines for the Prevention and Treatment of Type 2 Diabetes (2020 Edition) (19). Exclusion criteria included: (1) acute diabetic complications; (2) pregnancy or lactation; (3) significant cardiovascular/cerebrovascular diseases or severe hepatic/renal dysfunction; (4) history of thyroid surgery; (5) use of medications affecting thyroid function; (6) recent use of vitamin D supplements, glucocorticoids, calcium, or other agents influencing vitamin D levels; and (7) diagnosis of arthritis, recent fractures, metabolic bone disease, severe infections, malignancies, or anemia. The final analysis included 499 patients with sufficient vitamin D (≥30 ng/mL), 736 with insufficiency (20-29.9 ng/mL), and 570 with deficiency (<20 ng/mL).

According to established guidelines, the diagnostic thresholds for thyroid dysfunction are defined as follows: Hyperthyroidism is diagnosed when FT3 exceeds 6.8 pmol/L and/or FT4 exceeds 22 pmol/L with concomitant TSH levels below 0.27 mIU/L, while hypothyroidism is characterized by FT3 below 3.1 pmol/L and/or FT4 below 12 pmol/L with TSH levels above 4.2 mIU/L. Subclinical hypothyroidism presents with normal-range FT3 (3.1-6.8 pmol/L) and FT4 (12–22 pmol/L) but elevated TSH (>4.2 mIU/L), whereas subclinical hyperthyroidism shows similar normal FT3 and FT4 levels with suppressed TSH (<0.27 mIU/L). These criteria are further summarized as: (1) hyperthyroidism requires elevated FT3/FT4 with TSH below the lower reference limit; (2) hypothyroidism demonstrates decreased FT3/FT4 with TSH above the upper limit; (3) subclinical variants maintain normal FT3/FT4 but exhibit TSH abnormalities - elevated for hypothyroidism and suppressed for hyperthyroidism.

The demographic variables collected in this study included gender, age, height, weight, body mass index (BMI, calculated as weight in kilograms divided by height in meters squared), and blood pressure.

Following an 8–10 hour fasting period, comprehensive biochemical analyses were performed using a fully automated biochemical immunoassay analyzer. The assessed parameters included: fasting blood glucose (FBG), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), uric acid (UA), alanine transaminase (ALT), aspartate transaminase (AST), blood urea nitrogen (BUN), and creatinine. Plasma 25-hydroxyvitamin D [25(OH)D] levels, fasting C-peptide, and thyroid function parameters were quantified by electrochemiluminescence immunoassay (ECLIA).

According to established guidelines (20), serum 25-hydroxyvitamin D [25(OH)D] levels were categorized as follows: <20 ng/mL indicated deficiency; 20-29.9 ng/mL indicated insufficiency; and ≥30 ng/mL indicated sufficiency (21).

The data were analyzed using SPSS 20.0 (IBM Corp.). Normally distributed continuous variables were expressed as mean ± standard deviation and compared using independent t-tests. Non-normally distributed variables were presented as median (interquartile range) and analyzed with the Mann-Whitney U test. Spearman’s correlation analysis assessed monotonic relationships between variables. Logistic regression analysis identified factors significantly associated with categorical outcome variables. A p-value <0.05 was considered statistically significant.

Comparisons among the three vitamin D groups (deficient, insufficient, sufficient) were conducted for demographic and metabolic parameters, including age, sex, BMI, blood pressure (SBP, DBP), lipid profiles (TC, TG, HDL-C, LDL-C), UA, FBG, HbA1c, thyroid function (FT3, FT4, TSH), and fasting C-peptide levels. The analysis revealed statistically significant intergroup differences (p < 0.05) in age, sex distribution, TC, TG, UA, FBG, HDL-C, LDL-C, FT3, FT4, fasting C-peptide, and HbA1c levels ( Table 1 ).

Spearman correlation analysis was conducted to examine the relationships between serum 25-hydroxyvitamin D [25(OH)D] levels and various metabolic parameters, including sex, age, body mass index (BMI), blood pressure (systolic [SBP] and diastolic [DBP]), lipid profiles (total cholesterol [TC], triglycerides [TG], high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C]), uric acid (UA), glycemic indices (fasting blood glucose [FBG], hemoglobin A1c [HbA1c]), fasting C-peptide, thyroid function (free triiodothyronine [FT3], free thyroxine [FT4], thyroid-stimulating hormone [TSH]), and thyroid autoantibodies (thyroglobulin antibody [TGAb], thyroid peroxidase antibody [TPOAb], TSH receptor antibody [TRAb]). The analysis revealed significant positive correlations between [25 (OH)D] levels and age (r = 0.138, p < 0.001), HDL-C (r = 0.101, p < 0.001), FT3 (r = 0.243, p < 0.001), and fasting C-peptide (r = 0.114, p < 0.001). It should be noted that the apparent correlation with sex (coded as a binary variable) reflects group differences rather than a true linear relationship, suggesting the need for alternative statistical approaches appropriate for categorical variables. Significant inverse correlations were observed between [25(OH)D] levels and TC (r = -0.100, p < 0.001), TG (r = -0.178, p < 0.01), FBG (r = -0.107, p < 0.001), LDL-C (r = -0.068, p = 0.004), and HbA1c (r = -0.172, p < 0.001) ( Table 2 ). No statistically significant correlations were found between [25(OH)D] levels and thyroid autoantibodies: TGAb (r = -0.024, p = 0.522), TPOAb (r = -0.051, p = 0.178), or TRAb (r = -0.034, p = 0.374) ( Table 3 ).

Logistic regression analysis was performed to assess the association between multiple clinical factors and vitamin D status in patients with type 2 diabetes mellitus (T2DM), with vitamin D levels categorized as the dependent variable. The multivariable-adjusted model included sex as a categorical variable and the following continuous covariates: age, hemoglobin A1c (HbA1c), free triiodothyronine (FT3), total cholesterol (TC), triglycerides (TG), uric acid (UA), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), fasting blood glucose (FBG), and fasting C-peptide.

For vitamin D-sufficient patients (>30 ng/mL), significant positive associations were observed with male sex (odds ratio [OR] = 2.52, 95% confidence interval [CI]: 1.57-4.03), older age (OR = 1.05, 95% CI: 1.03-1.07), and higher FT3 levels (OR = 1.28, 95% CI: 1.00-1.62), while inverse associations were found with HbA1c (OR = 0.88, 95% CI: 0.79-0.98) and TG levels (OR = 0.68, 95% CI: 0.49-0.95). Among patients with vitamin D insufficiency (20-29.9 ng/mL), significant associations were identified for age (OR = 1.02, 95% CI: 1.00-1.03), FT3 (OR = 1.30, 95% CI: 1.04-1.62), and UA (OR = 0.998, 95% CI: 0.996-1.000) ( Table 4 ).

Multivariable logistic regression analysis was conducted to evaluate the association between clinical factors and thyroid function status in patients with type 2 diabetes mellitus. Thyroid function was categorized into five groups as the dependent variable: hyperthyroidism, hypothyroidism, subclinical hypothyroidism, subclinical hyperthyroidism, and euthyroidism (reference group). The model included sex as a categorical variable and the following continuous covariates: age, body mass index (BMI), serum 25-hydroxyvitamin D [25(OH)D] levels, hemoglobin A1c (HbA1c), fasting blood glucose (FBG), fasting C-peptide, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C).

The analysis revealed distinct patterns of association across thyroid dysfunction categories. Hyperthyroidism showed significant positive associations with lower vitamin D levels (OR = 1.07, 95% CI: 1.01-1.13) and inverse associations with age (OR = 0.93, 95% CI: 0.89-0.98) and BMI (OR = 0.74, 95% CI: 0.60-0.91). Hypothyroidism was positively associated with age (OR = 1.07, 95% CI: 1.01-1.13) and TC levels (OR = 1.07, 95% CI: 1.01-1.13). For subclinical hypothyroidism, significant inverse associations were observed with HbA1c (OR = 0.88, 95% CI: 0.80-0.97) and male sex (OR = 0.65, 95% CI: 0.44-0.96), while a positive association was found with uric acid levels (OR = 1.004, 95% CI: 1.002-1.005) ( Table 5 ).

Contemporary research has established that vitamin D’s physiological functions extend far beyond its classical role in calcium homeostasis. The near-ubiquitous expression of the vitamin D receptor (VDR) across human tissues and cell types underscores its pleiotropic effects on various biological systems (22, 23). Multiple longitudinal studies have demonstrated a significant inverse association between serum 25-hydroxyvitamin D [25(OH)D] concentrations and insulin resistance, a core pathophysiological mechanism underlying type 2 diabetes mellitus (T2DM) development. This relationship persists after adjustment for potential confounders including BMI, physical activity, and seasonal variation, suggesting an independent role of vitamin D in glucose metabolism regulation (10, 24, 25). Our findings demonstrate a significant positive association between serum 25-hydroxyvitamin D [25(OH)D] levels and fasting C-peptide concentrations (β = 0.24, p < 0.001), suggesting vitamin D sufficiency may be associated with preserved β-cell function in patients with type 2 diabetes mellitus (T2DM). This observation aligns with emerging evidence that vitamin D modulates both insulin secretion and sensitivity through multiple pathways, including: (1) direct effects on pancreatic β-cell VDR expression, (2) regulation of intracellular calcium flux in insulin-sensitive tissues, and (3) modulation of systemic inflammation. Conversely, we observed significant inverse correlations between serum 25-hydroxyvitamin D [25(OH)D] levels and multiple metabolic parameters: total cholesterol (TC: r = -0.100, p < 0.001), triglycerides (TG: r = -0.178, p < 0.01), low-density lipoprotein cholesterol (LDL-C: r = -0.068, p = 0.004), fasting blood glucose (FBG: r = -0.107, p < 0.001), and hemoglobin A1c (HbA1c: r = -0.172, p < 0.001). These consistent negative associations suggest vitamin D sufficiency may exert protective effects on lipid metabolism and glycemic control in patients with type 2 diabetes. The inverse relationship between serum vitamin D levels and both HbA1c and FBG is consistent with previous studies suggesting that vitamin D deficiency is associated with impaired glucose metabolism and an increased risk of diabetes. We performed logistic regression analyses to evaluate the influence of multiple clinical factors on vitamin D status in patients with type 2 diabetes mellitus (T2DM). HbA1c showed a significant negative association with serum 25-hydroxyvitamin D [25(OH)D] levels (OR = 0.878, 95% CI: 0.790-0.976), suggesting vitamin D may play a role in glucose homeostasis regulation and insulin sensitivity enhancement. Additionally, the observed inverse associations between serum 25-hydroxyvitamin D [25(OH)D] levels and both total cholesterol (TC) and triglycerides (TG) may reflect vitamin D’s regulatory role in lipid metabolism, potentially indicating a protective effect against dyslipidemia. Vitamin D is thought to influence insulin sensitivity through multiple mechanisms, including its involvement in calcium metabolism (26, 27), regulation of the renin-angiotensin system (28), and modulation of inflammation (29). Low serum levels of 25-hydroxyvitamin D have been associated with an increased risk of insulin resistance and the development of type 2 diabetes (7). The biochemical pathways through which vitamin D may modulate insulin sensitivity warrant further investigation, particularly regarding the role of chronic inflammation in metabolic dysfunction.

This study employed multivariable logistic regression to evaluate clinical factors associated with thyroid function. For subclinical hypothyroidism, the observed inverse association with HbA1c (OR = 0.879, 95% CI: 0.798-0.967) suggests better glycemic control may protect against subclinical thyroid dysfunction development, highlighting the bidirectional thyroid-glucose metabolism relationship. Thyroid hormones are well-established as key regulators of metabolic processes, including glucose metabolism. Thyroid dysfunction, particularly hypothyroidism, has been associated with impaired glucose tolerance and increased insulin resistance (30, 31). Conversely, hyperthyroidism may lead to enhanced glucose uptake and improved insulin sensitivity (32, 33). The interrelationship between thyroid function and glucose metabolism underscores the importance of assessing thyroid parameters in patients with type 2 diabetes mellitus (T2DM). Thyroid hormones may also regulate vitamin D metabolism by modulating the expression of enzymes involved in the conversion of vitamin D to its active form, 1,25-dihydroxyvitamin D [1,25(OH)2D] (34).

In this study, multivariable logistic regression analysis was performed to assess the clinical factors associated with thyroid function. The positive correlation between hyperthyroidism and serum vitamin D levels (OR = 1.069, 95% CI: 1.009–1.133) suggests that adequate vitamin D may contribute to the regulation of thyroid hormone. Additionally, the inverse relationship with age (OR = 0.935, 95% CI: 0.893–0.978) indicates that younger individuals are more likely to exhibit hyperthyroidism—a pattern that may be attributable to autoimmune conditions such as Graves’ disease, which predominantly affects younger populations. The observed inverse association between BMI and hyperthyroidism (OR = 0.738, 95% CI: 0.601-0.906) suggests that higher adiposity may confer a protective effect, possibly mediated through metabolic and hormonal mechanisms related to increased fat mass. Emerging evidence suggested vitamin D may play a regulatory role in thyroid function (35). Vitamin D primarily exerts its biological effects through the vitamin D receptor (VDR), which is expressed in various cell types, including thyroid follicular cells. Through VDR activation, vitamin D modulates thyroid cell proliferation, differentiation, and functional activity, thereby regulating thyroid hormone synthesis and secretion (36). In addition, vitamin D enhances the innate immune response through VDR activation. It exhibits immunoregulatory properties by modulating cytokine production, which may contribute to thyroid damage and dysfunction (37). Notably, the study found no significant correlations between serum vitamin D levels and thyroid-specific autoantibodies (TGAb, TPOAb, and TRAb), suggesting that the autoimmune component of thyroid dysfunction may not directly influence vitamin D status. Conversely, thyroid hormone levels appear to affect vitamin D metabolism, revealing a potential bidirectional relationship between thyroid function and vitamin D status. This interplay highlights the importance of simultaneous evaluation of vitamin D status and thyroid function when assessing type 2 diabetes risk. Clinically, it may be prudent to monitor vitamin D levels in patients with thyroid disorders and to evaluate thyroid function in individuals with vitamin D deficiency.

The findings from numerous studies underscore the importance of addressing vitamin D deficiency and thyroid dysfunction in the prevention and management of type 2 diabetes. Clinicians should consider routine screening of patients for vitamin D deficiency, especially in individuals at a elevated risk for developing type 2 diabetes and thyroid disorders. Furthermore, although vitamin D supplementation may offer clinical benefit in certain cases, the optimal dosage and duration of treatment remain to be clearly established.

While the existing literature offers valuable insights, several limitations remain. Notably, the predominance of cross-sectional study designs limits the ability to infer causal relationships. Furthermore, many studies include relatively homogeneous populations, which may limit the generalizability of their findings to broader, more diverse populations. Future research should prioritize well-designed longitudinal studies and randomized controlled trials to clarify the causal relationships between vitamin D status, thyroid function, and the development of type 2 diabetes. Elucidating the underlying mechanisms that link these factors will be essential for the development of targeted interventions in at-risk populations.