1. Introduction

Obesity has become a global epidemic that poses a tremendous challenge to healthcare management [1]. China currently bears the world’s highest obesity burden, with its prevalence rate experiencing a fivefold increase since 2004. This epidemiological shift correlates strongly with urbanization, sedentary lifestyles, and dietary transitions towards energy-dense foods [2]. Obesity increases the risk of major chronic diseases, such as type 2 diabetes [3], certain cancers [4], and cardiovascular disease (CVD) [5], which is the leading cause of morbidity and mortality globally. Moreover, an inverse association between vitamin D and obesity has been frequently observed, and increased vitamin D deficiency in obese patients has been reported as well [6]. Obesity-related vitamin D deficiency may stem from vitamin D sequestration in adipose tissue and insufficient cutaneous vitamin D synthesis due to diminished outdoor exposure.

25-hydroxyvitamin D [25(OH) D] is well known for its central role in calcium and phosphorous homeostasis and bone metabolism. In recent years, emerging evidence suggests that vitamin D has various extra-skeletal effects, particularly its roles in cardiomyocytes, vascular endothelium, vascular smooth muscles, and pancreatic beta-cells. [7, 8]. Many observational studies have reported that vitamin D deficiency is a major global health problem linked to CVD and cardiometabolic disease risk factors (obesity, hyperglycemia, hypertension, and dyslipidemia) [7, 9]. The interplay between vitamin D and obesity further exacerbates the effects of vitamin D deficiency on CVD development in patients with obesity. Nevertheless, the reported relationships between the vitamin D status and traditional CVD risk factors remain inconsistent [10]. Furthermore, one recent meta-analysis that included more than 83,000 individuals showed that vitamin D supplementation was not associated with reduced major adverse cardiovascular events [11]. To date, although substantial studies have investigated the association between the vitamin D status and cardiometabolic parameters in obese and overweight populations, evidence remains limited in individuals with extreme obesity-a subgroup at higher metabolic risk. Additionally, the relationship has not been adequately studied in specific ethnic populations and in Chinese adults in particular. Thus, in the present study, we aimed to evaluate whether serum vitamin D is related to cardiometabolic risk factors in extremely obese adults from North China.

2. Materials and Methods

3. Results

3.3. The Relationship Between Serum 25(OH) D and Metabolic Parameters

Spearman correlation analysis showed that total vitamin D was negatively associated with the BMI (r = −0.23, p < 0.0001) and PTH (r = −0.36, p < 0.0001) but was positively correlated with HDL-c (r = 0.14, p = 0.0162) and ApoA1 (r = 0.24, p = 0.0002) (Figure 1). In-line, multiple linear regression analysis indicated that a higher 25(OH) D level (crude analysis) was associated with higher HDL-c and ApoA1 (Table 3) as well. When adjusting for the confounders, age, sex, and BMI (model 1), the association between 25(OH) D and HDL-c and ApoA1 not only persisted but also became stronger. Finally, after additionally adjusting for HOMA-IR, the above-mentioned associations still remained significant (Model 2).

Table 3. Multiple linear regression analysis: independent effect of circulating 25(OH) D on lipids.

Variables		25(OH) D
		B	95% CI	p value
HDL-c	Crude	0.005	0.001 to 0.009	0.014
	Model 1	0.005	0.002 to 0.009	0.006
	Model 2	0.005	0.001 to 0.009	0.007
LDL-c	Crude	0.006	0.009 to 0.022	0.437
	Model 1	0.012	0.004 to 0.028	0.151
	Model 2	0.011	0.006 to 0.027	0.196
ApoA1	Crude	0.007	0.003 to 0.010	< 0.001
	Model 1	0.008	0.004 to 0.012	< 0.001
	Model 2	0.008	0.004 to 0.012	< 0.001
ApoB	Crude	0.001	0.003 to 0.005	0.487
	Model 1	0.002	0.002 to 0.006	0.347
	Model 2	0.002	0.003 to 0.006	0.463

• Note: LDL-c: low-density lipoproteins; HDL-c: high-density lipoproteins; ApoA1: Apolipoprotein A1; ApoB: Apolipoprotein B. Model 1: adjusted for age, sex, and BMI. Model 2: adjusted for age, sex, BMI, and HOMA-IR. p < 0.05 is highlighted in bold.

4. Discussion

Our study revealed an alarmingly high prevalence of vitamin D deficiency in a cohort of extremely obese adults from North China. Our findings showed that individuals with vitamin D deficiency exhibited a higher BMI and PTH and that serum 25(OH) D concentrations were significantly negatively related to the BMI and PTH. Furthermore, our study demonstrated that there was a strong positive association between 25(OH) D and HDL-c, even after adjusting for several confounders. We also found a positive association between serum 25(OH) D and ApoA1. However, no significant differences in other cardiometabolic risk factors (blood pressure, fasting glucose, fasting insulin, and HOMA-IR) between vitamin D nondeficient (≥ 20 ng/mL) and deficient (< 20 ng/mL) patients were observed.

High burden of vitamin D deficiency was observed in our study population, with fewer than 20% of subjects exhibiting serum 25(OH) D levels above the adequacy threshold of 20 ng/mL. Indeed, the poor vitamin D status has been reported previously in elderly Chinese individuals in Beijing, where 69.2% of participants showed 25(OH) D levels ≤ 50 nmol/L [13]. Similar to our findings, the Peking Vertebral Fracture study showed that the 25(OH) D levels of postmenopausal women in Beijing were remarkably low, with an average of only 13.2 ± 5.4 ng/mL [14]. Additionally, a study of adolescent girls in Beijing suggested that more than 40% of school-aged girls had 25(OH) D levels below 12.5 nmol/L [15]. These data demonstrate that vitamin D deficiency is common in both children and adults in Beijing, China.

In our cohort, several factors likely contributed to the high prevalence of the low vitamin D status, such as the relatively high latitude of Beijing (latitude 40° north), the popular use of umbrellas, hats, and sunscreens when outdoors, lack of physical activity due to obesity, and limited availability of vitamin D supplements or fortified foods in supermarkets. Therefore, we recommend routine vitamin D supplementation for individuals with obesity in North China.

Numerous observational studies have shown that vitamin D deficiency is positively associated with the BMI [16–18]. Evidence from a 45-year-old British birth cohort involving 7198 Caucasian subjects confirmed the inverse relationship between vitamin D and obesity [19]. A meta-analysis further substantiated the significant negative correlation between the vitamin D status and the BMI [20]. Moreover, researchers have reported that vitamin D is negatively associated with perirenal fat thickness - a validated indicator of visceral adiposity [21]. Cheng et al. similarly suggested that both subcutaneous adiposity and visceral adiposity are inversely related to vitamin D levels [22]. Consistent with previous studies, our results revealed that a decrease in 25(OH) D levels was associated with an increased BMI in extremely obese individuals. What is more, a meta-analysis involving 3153 participants reported that vitamin D supplementation had a beneficial and significant reduction in the BMI in the subgroups of Asian with an intervention duration of more than 6 months [23]. Current perspectives propose that increased adipose tissue volumes in obese people sequester fat-soluble vitamin D, decrease vitamin D bioavailability, and reduce the release of vitamin D into the circulation [24, 25]. Additionally, obese individuals usually have less outdoor physical activity and inadequate sun exposure, leading to reduced synthesis of vitamin D in the skin [26].

Current evidence also suggests that vitamin D plays a role in lipoprotein metabolism. Notably, our results indicated that a poor vitamin D status was associated with lower HDL-c levels independent of the BMI, age, sex, and HOMA-IR. This finding was concordant with other vitamin D and lipid association studies, which showed that higher vitamin D levels were associated with increasing serum cardioprotective HDL-c levels [27–29]. In one study of 7952 adults with overweight or obese, vitamin D deficiency was positively correlated with reduced HDL-c levels [30]. More specifically, a cross-sectional study explored the association between HDL particle composition and vitamin D levels in postmenopausal women and demonstrated that higher 25(OH) D levels were associated with the large HDL particle subclass, which plays a vital role in reverse cholesterol transport and contributes to athero-protective function [31]. Additionally, a large meta-analysis that assessed the pooled effect of vitamin D supplementation on lipids in 39 randomized controlled trials (RCTs) indicated that vitamin D supplementation significantly increased HDL-c [32]. However, another meta-analysis reported inconsistent results and found no significant effects on HDL-c after vitamin D supplementation in prediabetic individuals [33]. A recent systematic review also showed that vitamin D supplementation did not yield significant alterations in HDL-c in individuals with obesity or overweight [34]. In addition, a Serial Clinical Laboratory Data Study of more than 100,000 patients suggested that correcting for a vitamin D deficiency might not translate into clinically meaningful improvement in lipid profiles, although higher 25(OH) D levels were associated with higher HDL-c [35]. Therefore, rigorous RCTs are needed to clarify the causal relationship between the vitamin D status and cardiometabolic markers.

ApoA1, an important functional component of HDL-c, is associated with reduced CVD risk. The cardioprotective effects of ApoA1 are primarily mediated through facilitating reverse cholesterol transport and anti-inflammatory actions. Additionally, emerging evidence demonstrates that ApoA1 exerts regulatory effects on energy homeostasis in adipocytes. ApoA1-deficient mice exhibited greater body weight gain and adipose tissue accumulation relative to WT controls [36]. Obese individuals are characterized by reduced HDL-c and ApoA1 levels [30]. In the present study, we found that there was a positive relationship between serum 25(OH) D and ApoA1 levels after adjustment for potential confounders. This is in line with other studies that reported that ApoA1 was positively correlated with vitamin D in Korean cohorts [37] and in Chinese osteoporosis patients [38]. In vitro studies have also indicated that vitamin D receptors regulate ApoA1 gene expression [39]. A meta-analysis of 7 RCTs demonstrated that daily vitamin D supplementation significantly increased ApoA1 levels [40], but no significant correlation between 25(OH) D and LDL-c was found in our study. In fact, the relationship between vitamin D and LDL-c is controversial according to previous studies. Chacko et al. observed no significant associations between serum 25(OH) D and LDL-c in the WHI-CaD population [41]. In contrast, however, a recent large cross-sectional study of 15,600 healthy patients provided evidence of a significant negative correlation between 25(OH) D and LDL-c levels [42]. These inconsistent results may be partly explained by the variations in the participant health status, age, BMI, and ethnicity.

Several observational studies have also shown that vitamin D deficiency is associated with elevated blood pressure, plasma glucose, and insulin resistance [8, 13, 43, 44]. However, our data revealed no consistent correlation of 25(OH) D levels with other cardiometabolic risk markers. In line with our study, numerous other studies have also failed to find significant associations between 25(OH) D levels and glucose metabolism or insulin sensitivity in both healthy populations and individuals with obesity [27, 45]. Further larger-scale prospective studies focusing on adults with severe obesity are warranted to confirm these findings.

The strength of this study lies in its contribution to the growing evidence regarding the relationship between vitamin D and cardiovascular risk factors in extremely obese populations. Our findings underscore the importance of vitamin D deficiency as a clinical correlate of CVD. However, this study has several limitations. First, the cross-sectional design precludes establishment of causal relationships between vitamin D levels and cardiovascular risk factors. Second, the number of participants with vitamin D sufficiency was low, so we had to combine vitamin D insufficiency and sufficiency into one group, restricting our capacity to examine associations at higher vitamin D concentrations. Third, the lack of data on physical activity, sunlight exposure, and dietary habits may have introduced confounding bias. Finally, we only enrolled Han Chinese subjects from North China, so our results may not be generalizable to other ethnic populations and geographic regions.

5. Conclusion

In this study, we identified a high prevalence of vitamin D deficiency among extremely obese individuals in Beijing, China. Serum 25(OH) D concentrations were inversely associated with the BMI and positively associated with HDL-c and ApoA1. Given the established links between the elevated BMI, dyslipidemia, and cardiometabolic morbidity, targeted strategies to address vitamin D deficiency in this population are clinically warranted. Furthermore, multicenter RCTs with large sample sizes are required to elucidate the potential impact of vitamin D supplementation on cardiovascular risk modulation.

Conflicts of Interest

The authors declare no conflicts of interest.

Author Contributions

Yan Zhou was responsible for writing the original draft. Xiaojing Wang was responsible for data analysis and reviewing and editing the manuscript. Chunyan Wang and Zhixing Wang collected clinical data. All authors have approved this version of the manuscript.

Funding

The work was supported by the National Natural Science Foundation of China (no. 82000746) and the Beijing Hospitals Authority Youth Program (QML20210901).