European Journal of Cardiovascular Medicine

Cardiovascular diseases are the leading cause of death and morbidity globally in the general population, especially in people with DM [1]. The main features of type 2 diabetes also increase cardiovascular risk: dyslipidemia, oxidative stress, and chronic inflammation [2]. The coexistence of diabetes and cardiovascular diseases remains a public health dilemma despite the advent of improved diabetes management and cardiovascular therapies [3]. Evidence is now emerging which suggests that Vitamin D deficiency could potentially be a modifiable factor driving this increased risk [4].

The recognition of vitamin D, traditionally a molecule involved in maintaining calcium homeostasis and bone health, has been increased in metabolic and cardiovascular functions [5]. In addition to these roles, it possesses powerful anti-inflammatory and antioxidant properties, making it a key player in cardiac and metabolic health [6]. Vitamin D benefits calcium homeostasis and has been implicated in several adverse cardiovascular outcomes, such as hypertension, dyslipidemia, and endothelial dysfunction [7]. Other studies indicate that Vitamin D deficiency potentially worsens hypertension, dyslipidemia, and endothelial dysfunction, which function as essential factors for the development of CVD [8]. This connection is especially alarming in parts of the world, such as the East Coast of the US, where people are some of the most deficient in Vitamin D due to their higher exposure to the sun [9].

Yet, studies suggest that Vitamin D deficiency is disturbing hugely enough in some population cohorts, primarily attributed to indoor lifestyle and some cultural practices that prevent sun exposure [10]. In consideration of cardiovascular risk, there exists a unique population of individuals with diabetes that can be used to assess the associations between Vitamin D levels and adverse cardiovascular events [11]. Biomarkers, including high-sensitivity C-reactive protein (hs-CRP), lipoprotein-associated phospholipase A2 (Lp-PLA2), and lipid profiles, provide additional information concerning earlier diagnosis and treatment of cardiovascular diseases [12].

Another area with a significant knowledge gap is how Vitamin D status influences cardiovascular health in those with diabetes [13]. Although studies have shown associations regarding the relationship between Vitamin D deficiency and individual CVD risk factors, little is known about their interaction on a background of high-risk populations [14]. Moreover, the demography of subpopulations, like diets and lifestyles, needs local inquiry.

Therefore, the present study tries to fill this gap by evaluating the relationship between Vitamin D and cardiovascular risk factors in diabetic patients. We aimed explicitly to analyze the prevalence of Vitamin D deficiency in diabetic patients compared to healthy controls, the relationship between Vitamin D levels and standard cardiovascular risk factors like lipid profiles and blood pressure, the relation between Vitamin D levels and novel cardiovascular risk factors such as hs-CRP and Lp-PLA2, as well as to assess gender-specific trends regarding Vitamin D deficiency and impacts on cardiovascular risk. Assessing these aims will provide vital information to guide focused strategies to lower the risk of cardiovascular disease and its sequelae in patients with diabetes. This study seeks to contribute knowledge for targeted interventions and strategies addressing the excess of cardiovascular disease in populations with diabetes mellitus by fulfilling these objectives.

This cross-sectional study assesses the association of Vitamin D levels with cardiovascular risk factors in diabetic patients. A total of 240 participants were recruited: 120 diabetic sufferers and 120 wholesome controls matched for age and gender. The Institutional Ethics Committee approved this study, and it was by the ethics standards. All participants provided written informed consent before enrolment.

Study Population

Inclusion Criteria: Diabetic patients aged 35–65 with no history of chronic inflammatory or infectious diseases, cancer, or prolonged medication other than for diabetes. Healthy controls matched for age and gender with no history of diabetes or chronic illness.

Exclusion Criteria: Participants with acute or chronic illnesses unrelated to diabetes, those on prolonged medications for unrelated conditions, and individuals outside the specified age range.

Data Collection: The participants were recruited from three medical centers affiliated with Sevana Healthcare. Structured questionnaires and clinical examinations were used for data collection. The records included detailed demographic, medical, and lifestyle information, including diet, physical activity, and sun exposure. After an overnight fast, blood samples were collected to measure:

Serum vitamin D levels can be quantified using enzyme-linked immunosorbent assay (ELISA); hence, we assessed the vitamin D levels with the help of ELISA. Lipid profiles were evaluated using enzymatic colorimetric methods for total cholesterol, LDL, HDL, and triglycerides. The parameters related to glycemia (fasting blood glucose (FBS) and post-prandial blood glucose (PPBS)) were determined by the glucose oxidase-peroxidase method. Malondialdehyde (MDA) as a marker of oxidative stress was measured by thiobarbituric acid reactive substances (TBARS) assay. High-sensitivity immunoturbidimetric assays and ELISA kits measured novel cardiovascular risk markers such as high-sensitivity C-reactive protein (hs-CRP) and lipoprotein-associated phospholipase A2 (Lp-PLA2).

Statistical Analysis: SPSS software (Version 21.0) was used to analyze data. Demographic and clinical characteristics were summarized using descriptive statistics. Independent t-tests and chi-square tests for continuous and categorical variables were used to conduct comparative analyses between groups. Associations between serum Vitamin D and cardiovascular risk markers were examined with the determination of correlation coefficients. Statistical significance was defined as p < 0.05. To integrate detailed biochemical, clinical, and demographic data and explore the role of Vitamin D in cardiovascular health in diabetic patients, this method aimed at providing a comprehensive view of this relationship.

Univariate comparisons of the diabetic and control groups were statistically significant in all measured parameters (independent t-test for continuous variables and chi-square test for categorical variables). In diabetic patients (mean 12.5 ng/mL), Vitamin D levels were significantly lower than in healthy controls (mean 28.3 ng/mL p < 0.001). LDL levels were significantly higher in the diabetic group (mean: 135 mg/dL) than in controls (100 mg/dL, p < 0.001), whereas HDL levels were significantly lower (38 mg/dL vs. 55 mg/dL, p < 0.001). Triglycerides were higher in diabetic patients (180 mg/dL) than controls (120 mg/dL, p < 0.001).

The levels of inflammatory markers like hs-CRP were significantly higher in the diabetic group (mean: 4.5 mg/L) than in controls (mean: 2.0 mg/L, p < 0.01). Likewise, the oxidative stress markers malondialdehyde (MDA) and a new cardiovascular risk marker, Lp-PLA2, were significantly higher in diabetics (250 ng/mL) versus controls (180 ng/mL, p < 0.01). There were strong inverse correlations between Vitamin D levels and cardiovascular risk markers. For example, the concentration of vitamin D was negatively correlated with those of LDL levels (r = -0.65, p < 0.001), hs-CRP (r = -0.58, p < 0.001), and SBP (r = -0.52, p < 0.001). Moreover, we also noted a positive correlation between Vitamin D levels and HDL (r = 0.48, p < 0.01), which suggests a protective role of Vitamin D regarding HDL levels.

Analyzed separately for sex, it was found that women had a higher prevalence of vitamin D deficiency (mean: 65%) than men (mean: 45%, p < 0.05). This provides evidence for gender differences having been affected by cultural and lifestyle behaviors like wearing traditional attire that covers all but the hands and face, low outdoor activities, and limited nutritional sources of vitamin D. Those practices increase the possibility of deficiency, especially among women, and are indicative of the public health policy that still needs to be conducted.

These statistical findings highlight the significant consequences of vitamin D deficiency on cardiovascular risk in diabetic populations. Strong correlations exist between Vitamin D levels and the key biomarkers that correlate as potentially modifiable risk factors with Cardiovascular health. This is also corroborated by the differences between diabetic cases and non-diabetic controls, highlighting the opportunity for public health measures.

Table 1: Comparison of Key Parameters Between Groups

Table 2: Gender-Specific Prevalence of Vitamin D Deficiency

The bar chart summarizes the data, revealing significant differences between diabetic patients and healthy controls for multiple metrics. The second bar chart shows the gender-specific prevalence of Vitamin D deficiency, suggesting that gender-tailored interventions are necessary.

This study showed that vitamin D deficiency is essential in contributing to cardiovascular risk in diabetic patients. Compared with healthy controls, vitamin D levels were significantly lower in diabetic individuals, whereas cardiovascular risk factors, including LDL, triglycerides, hs-CRP, and Lp-PLA2, were considerably higher in cases. Within the gender-specific analysis, the prevalence of Vitamin D deficiency was more common among women due to cultural and lifestyle influences.

The discovery adds to existing research identifying a connection between Vitamin D deficiency and cardiovascular risk. For example, Argano et al. (2018) also found inverse relationships between Vitamin D levels and inflammatory markers in patients with diabetes, highlighting the importance of Vitamin D in reducing systemic inflammation [15]. Han et al. (2021) also found that low Vitamin D levels were associated with elevated LDL and triglyceride levels, consistent with the lipid profile abnormalities we observed in this study [16].

In contrast, the higher levels of Lp-PLA2 reported in this study are inconsistent with Zhang et al. (2020), who found no significant relationship between Vitamin D deficiency and Lp-PLA2 [17]. These differences could be related to population demographics, dietary habits, and sunlight exposure. This also speaks to differences in genetic predisposition and baseline Vitamin D levels by study cohort and suggests cohort-specific investigations are warranted.

The patterns of gender-specific trends we observed may correlate with reports by Grantbet al. (2018), who noted that cultural practices like traditional dress and less time spent in the sun are the leading causes of Vitamin D deficiency in women [18].  In addition, they were not the first to suggest that estrogen may have a role in vitamin D metabolism, as experimental evidence in mammal species has shown. This study extends the work on the role of hs-CRP and Lp-PLA2 to the dual context of traditional cardiovascular risk factors and very novel markers of systemic inflammation. These types of global profiling confirm earlier findings and provide new insight into the effects of vitamin D deficiency on cardiovascular risk through diverse mechanisms. Future research needs to explore these associations, particularly in longitudinal designs, to establish causality and test the effectiveness of Vitamin D supplementation in different population sub-groups.

One major strength of this study is the comprehensive assessment of traditional and novel cardiovascular risk markers providing evidence for a link between Vitamin D and cardiovascular outcomes in the population living with diabetes. Analysis of gender-specifics has been included to delve deeper and identify priority areas for targeted interventions. However, the study’s cross-sectional design precludes establishing causality. Other limitations are possible confounding factors such as unmeasured dietary intake and genetic dispositions and the small sample size, which may restrict the generalizability of the results.

This study demonstrates the importance of Vitamin D deficiency correction as a modifiable cardiovascular risk factor, known as dyslipidemia, hypertension, smoking, or diabetes. Routine assessment of Vitamin D levels, supplementation, and lifestyle alteration interventions are highly recommended to reduce cardiovascular risk. Longitudinal studies are warranted to confirm these associations and explore vitamin D supplementation's therapeutic promise in preventing cardiovascular complications.

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