European Journal of Cardiovascular Medicine

Impaired glucose metabolism is linked to a higher likelihood of developing various chronic illnesses, such as obesity, Type 2 diabetes (T2DM), metabolic syndrome, and cardiovascular disease [1]. Both genetic predispositions and bad lifestyles might contribute to the development of hyperglycaemic problems. The precise genetic cause of hyperglycaemia has not yet been determined. However, there is strong evidence indicating that obesity, bad dietary habits, and a lack of physical activity are the primary non-genetic risk factors that may be modified. While dietary adjustment is considered a crucial initial treatment for hyperglycaemia, its efficiency is rather moderate [2,3]. In recent times, there has been increased focus on nutritional adjuvant medicines, such as chromium [4], magnesium [5], omega-3 fatty acids [6], and vitamin C [7], as a result of the negative effects of pharmaceutical treatments. Vitamin D has been extensively researched in clinical practice for its therapeutic properties, among other substances [8,9]. Vitamin D, a fat-soluble vitamin, is widely recognised for its role in controlling bone metabolism and maintaining calcium-phosphorus balance [9].

Moreover, it provides a range of non-skeletal advantages, primarily in the management of various chronic illnesses [10,11]. Vitamin D insufficiency is associated with aberrant glucose metabolism, modified insulin secretion, and type 2 diabetes mellitus (T2DM) [12]. The prevalence of vitamin D insufficiency is high among patients with type 2 diabetes mellitus (T2DM) [13]. Mitri et al. [14] discovered that a small rise in vitamin D consumption, from less than 5 mcg/day (200 IU/days) to 12.5 μgr/day (more than 500 IU/days), resulted in a 13% decrease in the likelihood of developing T2DM. Vitamin D deficiency in patients with type 2 diabetes mellitus (T2DM) might hinder the production of insulin, resulting in aberrant glucose metabolism and insulin resistance [15, 16]. Furthermore, other investigations have documented the hypoglycaemic effects of vitamin D [17–19]. Vitamin D provides protection against problems associated with diabetes by exerting antioxidant, anti-inflammatory, and immunomodulating actions, which are crucial in managing insulin resistance [9]. Multiple human investigations on diabetes have uncovered the advantageous effects of vitamin D on glycaemic management [20–22]. Furthermore, there is much data suggesting that vitamin D has the potential to lower lipid concentrations, enhance immunological modulation, and diminish oxidative stress [23, 24].

This prospective cohort study was conducted from January 2020 – December 2023 among type 2 diabetes mellitus (T2DM) patients who visited the outpatient department of Index Medical College, Hospital & Research Centre. (Malwanchal University, Indore, Madhya Pradesh). The biochemical assessments were carried out at the department of Biochemistry, Index Medical College, Hospital & Research Centre.

Type 2 diabetes mellitus (T2DM) individuals of both genders aged between 40 to 60 years with a diabetes duration of one to ten years and no history of established coronary artery disease were included in the study, while T2DM individuals who were on insulin and statin therapy, vitamin D supplementation, subjects with any acute or chronic illness as documented by history and individuals who were diagnosed with thyroid abnormality, cardiac, hepatic and renal dysfunction were excluded.

The comparison of demographic and clinical parameters across three groups revealed notable differences. Group I comprised 85 individuals, Group II had 10, and Group III also had 10 participants, totalling 105 individuals. Group II showed significantly lower weight and BMI compared to Group I, with p-values less than 0.001. Moreover, individuals in Group III demonstrated the highest weight and BMI among the groups. Blood pressure (SBP) was significantly higher in Group III compared to Group II (p = 0.03*). Group I had the longest duration of diabetes compared to the other groups (p < 0.001). Notably, Group III exhibited significantly higher levels of Vitamin D compared to Groups I and II, indicating potential differences in metabolic and health profiles among the groups. These findings suggest that demographic and clinical parameters vary significantly across the groups, indicating potential implications for further investigation and tailored management strategies.

Table 2 presents a comparison of lipid ratios across three groups (Group I, Group II, and Group III) and their total, consisting of 105 individuals. Lipid ratios including TC/HDL, APOB/A, LDL/HDL, TG/HDL, AIP, Sd-LDL, N-HDL-C, and N-HDL/HDL were examined. Significant differences were observed in APOB/A ratios (p = 0.02), indicating variation in atherogenic potential across the groups, while other ratios showed no significant differences. Overall, the table provides insights into lipid profile variations among the groups, which could be relevant for understanding cardiovascular risk factors and informing clinical interventions.

Table 3 illustrates the restoration of vitamin D sufficiency after follow-up across three groups (Groups I, II, and III), detailing the total number of individuals and their gender proportions. In Group I, out of 38 individuals, 31 (83%) attained vitamin D sufficiency, with a male to female proportion of 20 (65%) to 11 (35%). Six individuals (17%) remained insufficient in vitamin D levels, with a male to female proportion of 4 (62%) to 2 (38%). In Group II, all 7 individuals (100%) achieved vitamin D sufficiency, with a male to female proportion of 4 (64%) to 3 (36%). Conversely, in Group III, none of the 7 individuals attained sufficiency, all remaining insufficient, with a male to female proportion of 4 (64%) to 3 (36%). This table provides a clear overview of the restoration of vitamin D sufficiency, indicating notable differences across the groups and gender proportions.

Table 4 displays the clinical and demographic parameters of individuals in the vitamin D deficient group at baseline and follow-up, along with the percentage change (% change) and associated p-values. The parameters include age, gender distribution, height, weight, BMI, hypertension status, systolic blood pressure (SBP), diastolic blood pressure (DBP), and vitamin D levels.

Vitamin D deficiency (VDD) has been linked to various chronic conditions such as diabetes, cardiovascular complications, infectious diseases, autoimmune diseases, and cancer over the last twenty years. Multiple epidemiological studies provide evidence for the non-skeletal advantages of vitamin D, which should not be disregarded. However, it is important to note that many of these studies have limitations in their research methodologies, such as being observational, cross-sectional, or small randomized controlled trials.  [25,26]. Moreover, there exists a lack of agreement between the results obtained from observational studies and randomized trials regarding the impact of vitamin D on cardiovascular health. There is a limited number of studies that specifically examined the beneficial impacts of vitamin D supplementation on cardiovascular health, and there is a significant variation in the data obtained from secondary analyses. This highlights the importance of conducting well-planned studies on a global scale, using strong and trustworthy statistical methods, to produce reliable evidence regarding the cardiovascular advantages of vitamin D supplementation. This is especially crucial for high-risk populations, both for preventive measures and as supplementary therapy.

Predominance of Vitamin D Deficiency (VDD) among T2DM Patients

The evaluation of serum 25(OH)D levels at the beginning indicated a significant prevalence (81%) of vitamin D deficiency (VDD), with only 9.5% of individuals having sufficient levels of vitamin D and another 9.5% having insufficient levels. The given information is represented by Figure 8. The observed higher prevalence of vitamin D deficiency (VDD) is consistent with previous studies that have shown individuals with type 2 diabetes (T2DM) to have twice the rate of VDD compared to non-diabetic individuals. [27, 28, 29, 30]. Type 2 diabetes mellitus (T2DM) combined with vitamin D deficiency (VDD) increases the relative risk of developing cardiovascular diseases (CVDs) and mortality by two-fold, compared to diabetes with adequate vitamin D levels. [31,32]. Common factors contributing to vitamin D deficiency (VDD) in seemingly healthy individuals include inadequate dietary consumption and a sedentary lifestyle characterized by limited exposure to sunlight. The prevalence of vitamin D deficiency (VDD) in the study population is primarily caused by obesity, as evidenced by a significant negative correlation between serum 25(OH)D levels and body mass index (BMI). Additionally, a longer duration of diabetes is also associated with lower serum vitamin D levels. In other words, both an increase in BMI and a longer duration of the disease are linked to a decrease in vitamin D status.

The guidelines set by the Indian Consensus Group for Asian Indians living in India suggest a body mass index (BMI) threshold of 23 kg/m2 for overweight and 25 kg/m2 for obesity. [33]. The groups with vitamin D deficiency and insufficiency had a body mass index (BMI) of 29.3 kg/m2 and 26.27 kg/m2, respectively, indicating that they are obese individuals with type 2 diabetes mellitus (T2DM). The data presented in Table 10 and the visual representation in Figure 9 Obesity is characterized. Having a high BMI or waist circumference is also a significant risk factor for vitamin D deficiency (VDD). [34]. Due to its fat solubility, Vitamin D is extensively stored in adipose tissue, resulting in a decrease in its levels in the bloodstream. Additional potential causes for the observed VDD may include decreased levels of vitamin D binding protein (VDBP) due to impaired megalin function or limited availability, resulting in accelerated metabolism and elimination of vitamin D3. [35]

Serum vitamin D Levels and Lipid abnormalities at Baseline

Diabetic dyslipidaemia is identified by the existence of atypical lipoproteins, specifically elevated triglycerides (TGs), reduced levels of high-density lipoprotein-cholesterol (HDL-C), and an increase in small dense low-density lipoprotein (Sd-LDL) particles.[36] The disparity between elevated sd-LDL and decreased HDL plays a pivotal role in the development of atherosclerosis. [37,38] In addition, the reduced functionality of HDL caused by oxidative damage to apolipoprotein A-1 and the decreased activity of HDL-bound paraoxonase-1 in the diabetic environment also contribute to coronary artery disease (CAD). [39,40]. When compared to the other two groups, the vitamin D deficient category (group I) exhibited a statistically insignificant, nonlinear increase in serum Triglycerides, LDL-C, and apoB levels. In the same way, individuals in group I have lower levels of HDL-C and apolipoprotein A1 (apoA1) . This causes a shift in the balance towards atherogenicity.

When a person's total lipid profile appears to be normal, certain lipid ratios can be used as diagnostic alternatives to predict the risk of developing cardiovascular events. These ratios include CRI (Castelli's risk index) - which is the ratio of total cholesterol to HDL cholesterol (TC / HDL-C), CRI-II - the ratio of LDL cholesterol to HDL cholesterol (LDL-C / HDL-C), AIP (atherogenic index of plasma) - calculated as the logarithm of the ratio of triglycerides to HDL cholesterol (Log (TG / HDL-C)), AC (atherogenic coefficient) - the ratio of non-HDL cholesterol to HDL cholesterol (N-HDL / HDL-C), and ApoB / A. [ 41,42 ]With the exception of the ApoB/A ratio, where group I showed a significantly higher ratio compared to group II, there were no significant differences observed in the lipid indices among the different vitamin D categories.

Administering vitamin D to individuals with type 2 diabetes mellitus (T2DM) who have had the disease for less than 10 years, and have insufficient levels of the vitamin, led to the restoration of normal health. The restoration resulted in enhanced cardio-metabolic health, as indicated by the favourable impact on glycaemic markers (specifically insulin and HOMAIR) and comprehensive lipid profile (triglycerides, ApoB/A, Sd-LDL, N-HDL, AIP). The beneficial effects were particularly evident in individuals with profound deficiencies. The impact on inflammatory markers is negligible and is statistically significant solely in the cohort with inadequate levels of vitamin D (supplementation led to a discernible reduction in VCAM), underscoring the significance of initial 25(OH)D levels on particular outcomes. The simultaneous decrease in serum 25 (OH) D levels in the sufficient group highlights the importance of vitamin D supplementation for maintaining sufficiency.

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