Original Article

Volume 15, Number 2, April 2025, pages 58-63

Association of Vitamin D Serum Levels With Glycemic, Lipid Profiles, and Diabetic Complications in Saudi Type II Diabetes Patients

Vitamin D is a lipid-soluble vitamin that plays a major role in human homeostasis [1]. It regulates the level of calcium in the blood through enhancing its absorption and decreasing its elimination [2].

The normal range of total vitamin D, which refers to the sum of both vitamin D forms in adult human serum, is between 50 and 125 nmol/L. A deficiency in vitamin D is considered when its serum level is below 50 nmol/L [3]. It was reported that deficiency in vitamin D has been associated with some human diseases, such as cancers and autoimmune diseases [4], and with the severity of coronavirus disease 2019 (COVID-19) disease symptoms [5]. In addition, genetic variants in vitamin D receptor (VDR) gene were associated with type I diabetes mellitus (DM) [6] and the complications of type II DM [7].

The prevalence of vitamin D deficiency is high in Saudi Arabia. A meta-analysis study reported that the overall vitamin D deficiency in the healthy Saudi Arabian population is 60% [8]. However, it was shown by Al-Humaidi et al that there is no difference in the frequency of vitamin D-deficient individuals among type II diabetic and non-diabetic among Saudi volunteers [9].

Diabetes is an increase of blood glucose level. It is classified into type I, type II, and gestational diabetes. The prevalence of type II DM is high among the developing countries particularly in Saudi Arabia [10].

It was found that vitamin D increases the ability of beta pancreatic cells to produce insulin and increases the insulin sensitivity in the peripheral tissues [11]. In addition, it is reported that vitamin D has an anti-inflammatory and anti-oxidant activity, therefore it may protect the body organs from the oxidative stress and inflammation induced by high glucose levels [12]. Accordingly, vitamin D deficiency can exacerbate the DM complications, such as neuropathy, retinopathy, and nephropathy.

To the best of our knowledge, there is lack of information regarding the influence of vitamin D level deficiency on the type II DM complications among Saudi patients. Therefore, this study aimed to find out the association of total serum vitamin D levels with the glycemic and lipid profiles and with the major type II DM complications among Saudi patients living in the capital city, Ar-Ryiadh.

This retrospective, cross-sectional study was conducted at a network of tertiary private hospitals in Saudi Arabia. The study period spanned from January 2019 to June 2023, aiming to assess the association of serum vitamin D levels with glycemic control, lipid profiles, and DM complications among type II DM patients.

Data were collected from the electronic medical records (EMR) of 500 type II DM patients. Patient information was sourced from clinical records, laboratory results, nursing notes, and documented clinical outcomes. To ensure accuracy and uniformity in data gathering, a standardized data collection form was utilized, designed to capture relevant clinical and laboratory parameters comprehensively.

The collected data included demographic details (age and gender), clinical measurements (weight and blood pressure), and biochemical markers such as fasting blood glucose, HbA1c, lipid profiles (HDL, LDL, and triglycerides), and serum vitamin D levels. Additionally, DM complications, including neuropathy, nephropathy, and retinopathy, were documented based on clinical diagnoses by specialists in the hospital.

The thresholds that define vitamin D status are typically based on serum concentrations of 25-hydroxyvitamin D (25(OH)D), according to the guideline of the Endocrine Society and the Institute of Medicine that sufficient vitamin D level is ≥ 30 ng/mL (or ≥ 75 nmol/L), while deficient vitamin D level is less than 20 ng/mL [13]. This is also the protocol of classification of vitamin D deficiency used by Dr. Sulaiman Al-Habib Medical Group, Riyadh, Saudi Arabia.

Patient data were retrieved through the VIDA System, a secure healthcare platform widely implemented across both public and private healthcare sectors in Saudi Arabia. All data were de-identified prior to retrieval to ensure confidentiality and privacy, adhering to stringent data protection standards. After extraction, data were organized and stored in Microsoft Excel for cleaning, processing, and subsequent statistical analysis.

Approval for this study was obtained from the Institutional Review Board at Al Habib Research Center, Dr. Sulaiman Al-Habib Medical Group, Riyadh, Saudi Arabia (IRB Log No: RC22.10.03). The study adhered to ethical guidelines for research involving human subjects, with all procedures conforming to the Declaration of Helsinki. Informed consent was waived due to the retrospective nature of the study, and all data were anonymized to protect patient identities.

Data were analyzed to identify the associations between serum vitamin D levels and various biochemical and clinical parameters. The normality of continuous variables was assessed using Shapiro-Wilk test. All P-values were greater than 0.05. These indicate that continuous data collected from the participants are normally distributed, justifying the use of parametric tests. Pearson correlation analysis was used to assess the linear relationship between continuous variables and serum vitamin D levels. The Student’s t-test was used to compare the mean of two groups. Additionally, Chi-square tests (χ²) were used to examine the association between categorical variables. All analyses were performed using SPSS software (version 26, USA), with a significance level set at P < 0.05.

The sample size was calculated using MedCalc^® Statistical Software version 22.018 (MedCalc Software Ltd, 2024), based on an assumed statistical power of 80%, a 5% margin of error, and a population size of more than 10,000 DM patients in Saudi Arabia. The minimum required sample size was determined to be 382 participants. Our study included a total of 500 patients, exceeding this requirement and thereby enhancing the statistical robustness and generalizability of the findings.

The study included a total of 500 participants, comprising 259 females and 241 males. The average age of the participants was 61.17 ± 11.35 years.

Regarding biochemical markers, the overall mean HbA1c level was 7.09 ± 1.63. The average body mass index (BMI) and systolic blood pressure were 30 ± 8.5 kg/m² and 123 ± 18 mm Hg, respectively. The mean vitamin D level for all participants was 46.13 ± 28.74 nmol/L, and 410 (82%) participants were classified as vitamin D deficient.

The average values of the lipid profile parameters LDL, HDL, and total cholesterol of the participants were 2.73 ± 1, 1.2 ± 0.4, and 4.5 ± 1.7 mmol/L, respectively.

The average values of the biochemical profile parameters uric acid, blood urea nitrogen, and blood creatinine among the participants were 318 ± 90 µmol/L, 5.5 ± 2.1 mmol/L, and 72 ± 21 µmol/L, respectively.

Regarding the association of vitamin D levels with the anthropometric parameters of the patients, it was found that total vitamin D levels were significantly (P < 0.05) correlated and inversely with the weight of the patients and directly with the age of the patients (Table 1).

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Table 1. Association of Vitamin D Levels With Anthropometric Parameters

The Chi-square test between the gender of the DM patients and vitamin D levels showed that female DM patients had significantly (χ² = 19.6, P < 0.001) more vitamin D levels in comparison with male patients (Table 2). Additionally, the mean HDL level among patients with low vitamin D levels was significantly lower (t-test, P < 0.001) than that in patients with normal vitamin D levels (Table 2). In addition, the average age of vitamin D-deficient patients (56.4 ± 11.5 years) was significantly lower (P = 0.02) than that of the patients with normal levels (61.2 ± 8 years). The mean values of other lipid biomarkers, HbA1c, creatinine, uric acid, blood urea nitrogen, and BMI were not statistically (t-test, P < 0.001) different between the two groups: deficient and normal vitamin D levels.

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Table 2. Baseline Characteristics by Vitamin D Status Among Diabetic Patients

Table 3 shows the correlation of vitamin D levels with the glycemic and lipid profiles of the DM patients. It was shown that only HDL was significantly (P < 0.001) correlated with the level of total serum vitamin D among the patients.

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Table 3. Correlation of Vitamin D Levels With Glycemic and Lipid Profiles

There was no significant correlation (P > 0.05) between the level of total vitamin D with uric acid, blood urea nitrogen, and serum creatinine, as represented in Table 3.

Table 4 shows that only the DM complication neuropathy was significantly (P < 0.05) associated with the vitamin D levels, where patients with vitamin D deficiency were more likely to develop neuropathy than patients with normal vitamin D levels.

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Table 4. Binary Regression Between Vitamin D Levels and Diabetic Complications

The deficiency in vitamin D levels in human is associated with many diseases. However, little is known about the association of vitamin D levels with the DM complications among Saudi population. In this study, we investigated the association of vitamin D with the anthropometric, glycemic, and lipid profiles, in addition to the major DM complications. We found that increased levels of vitamin D are significantly associated with the female gender, increased patient’s age, increased HDL level, and a lower prevalence of neuropathy among the DM volunteers. These results can increase our understanding of the role of vitamin D in the pathophysiology of DM.

Some studies reported that deficiency in vitamin D is more frequent among Arab females than males [14]. In contrast, we found in this study that female DM patients have higher levels of vitamin D than male patients. Interestingly, we found in this study that the level of vitamin D is directly correlated with the patients’ age. These results may suggest that older women use oral vitamin D supplements as a prophylactic and therapeutic measure against menopause-induced osteoporosis [15].

We found in the current study that the level of vitamin D is inversely correlated with the patients’ body weight. It was reported previously that obese people have a significant lower levels of vitamin D in comparison with non-obese individuals [16]. This might indicate that vitamin D regulates the lipid metabolism. Yang et al showed that vitamin D increases the lipid metabolism through inhibiting parathyroid hormone secretion [17].

Several studies showed that vitamin D increases the level of HDL and decreases the levels of LDL and triglycerides [1, 18]. In the current study, we did not find a significant correlation between the level of vitamin D and LDL; however, there is a positive correlation between serum vitamin D and HDL level. This finding is in contrast with what was reported previously by Alkhatatbeh et al [19]. This may indicate the importance of confirming these findings using a larger sample size. Al-Hawari et al reported that the promoter region of Apolipoprotein A gene that expresses the protein component of HDL has multiple binding sites of vitamin D receptor.

We did not find in this study any significant correlation between the level of vitamin D and DM biomarkers. This finding agrees with what was reported previously that vitamin D deficiency was not associated with type II DM among Saudi patients [10].

The results of this study showed that decreased levels of vitamin D are significantly associated with a higher prevalence of neuropathy among the DM patients. It was reported that vitamin D reduces the oxidative stress, the major cause of hypertension and neuro-damage which could explain its potential protective association with DM complications. Al-Hawari et al reported that VDR genetic variants were associated with the retinopathy complication among Arabic DM patients in Jordan [7].

Although a statistically significant association was found between vitamin D deficiency and the presence of neuropathy, the small number of cases in this subgroup may reduce the strength of this finding. Therefore, further studies with larger sample size of DM neuropathy complication are needed to confirm this association.

There are some limitations in this study. First, because it is a retrospective and cross-sectional study, we cannot confirm a cause-and-effect relationship. Second, the design of this study did not include data about the type of diet, medications administrated by the participant patients, and the exposure to sun light. The diet and medication can affect the lipid, glycemic, and vitamin D levels [20]. In addition, this study included only patients from the capital city in the center region of Saudi Arabia and did not include other parts in Saudi Arabia. Finally, even though we adjusted for some important factors, there may still be other hidden factors that might influence the results.

In conclusion, this study found the significant association between vitamin D levels and various clinical parameters in type II DM patients in Saudi Arabia. Vitamin D levels were linked to age, gender, HDL levels, and higher prevalence of neuropathy. Despite no significant correlation with glycemic markers, the protective role of vitamin D against DM complications was found. However, the study’s limitations warrant further research with a larger, more diverse population to confirm these findings.

Acknowledgments

The authors would like to thank Dr. Sulaiman Al-Habib Medical Group in Riyadh, Saudi Arabia, for their support in this research.

Financial Disclosure

This work was funded by King Abdulaziz City for Science and Technology, Riyadh.

Conflict of Interest

Authors declare that there is no conflict of interest.

Informed Consent

Informed consent was obtained from all participants in this study.

Author Contributions

Study conception and design: YFJ and YJ; data collection: JA; analysis and interpretation of results: YFJ and YJ; draft manuscript: YFJ, YJ, and JA. All authors reviewed the results and approved the final version of the manuscript.

Data Availability

The data supporting the findings of this study are available from the corresponding author upon reasonable request.

Abbreviations

25(OH)D: 25-hydroxyvitamin D; BMI: body mass index; DM: diabetes mellitus; EMR: electronic medical records; HbA1c: hemoglobin A1c; HDL: high-density lipoprotein; IRB: Institutional Review Board; LDL: low-density lipoprotein; SPSS: Statistical Package for the Social Sciences; VDR: vitamin D receptor

1. Surdu AM, Pinzariu O, Ciobanu DM, Negru AG, Cainap SS, Lazea C, Iacob D, et al. Vitamin D and its role in the lipid metabolism and the development of atherosclerosis. Biomedicines. 2021;9(2):172.
   doi pubmed
2. Bikle DD. Vitamin D metabolism, mechanism of action, and clinical applications. Chem Biol. 2014;21(3):319-329.
   doi pubmed
3. Cui A, Zhang T, Xiao P, Fan Z, Wang H, Zhuang Y. Global and regional prevalence of vitamin D deficiency in population-based studies from 2000 to 2022: A pooled analysis of 7.9 million participants. Front Nutr. 2023;10:1070808.
   doi pubmed
4. Yang CY, Leung PS, Adamopoulos IE, Gershwin ME. The implication of vitamin D and autoimmunity: a comprehensive review. Clin Rev Allergy Immunol. 2013;45(2):217-226.
   doi pubmed
5. Alhammadin G, Jarrar Y, Madani A, Lee SJ. Exploring the influence of VDR genetic variants TaqI, ApaI, and FokI on COVID-19 severity and long-COVID-19 symptoms. J Pers Med. 2023;13(12):1663.
   doi pubmed
6. Zhai N, Bidares R, Makoui MH, Aslani S, Mohammadi P, Razi B, Imani D, et al. Vitamin D receptor gene polymorphisms and the risk of the type 1 diabetes: a meta-regression and updated meta-analysis. BMC Endocr Disord. 2020;20(1):121.
   doi pubmed
7. Alhawari H, Jarrar Y, Abulebdah D, Abaalkhail SJ, Alkhalili M, Alkhalili S, Alhawari H, et al. Effects of vitamin D receptor genotype on lipid profiles and retinopathy risk in type 2 diabetes patients: a pilot study. J Pers Med. 2022;12(9):1488.
   doi pubmed
8. Al-Alyani H, Al-Turki HA, Al-Essa ON, Alani FM, Sadat-Ali M. Vitamin D deficiency in Saudi Arabians: a reality or simply hype: A meta-analysis (2008-2015). J Family Community Med. 2018;25(1):1-4.
   doi pubmed
9. Alhumaidi M, Agha A, Dewish M. Vitamin d deficiency in patients with type-2 diabetes mellitus in southern region of saudi arabia. Maedica (Bucur). 2013;8(3):231-236.
   pubmed
10. Jarrar M, Abusalah MAH, Albaker W, Al-Bsheish M, Alsyouf A, Al-Mugheed K, Issa MR, et al. Prevalence of type 2 diabetes mellitus in the general population of Saudi Arabia, 2000-2020: a systematic review and meta-analysis of observational studies. Saudi J Med Med Sci. 2023;11(1):1-10.
    doi pubmed
11. Argano C, Mirarchi L, Amodeo S, Orlando V, Torres A, Corrao S. The role of vitamin D and its molecular bases in insulin resistance, diabetes, metabolic syndrome, and cardiovascular disease: state of the art. Int J Mol Sci. 2023;24(20):15485.
    doi pubmed
12. Gu JC, Wu YG, Huang WG, Fan XJ, Chen XH, Zhou B, Lin ZJ, et al. Effect of vitamin D on oxidative stress and serum inflammatory factors in the patients with type 2 diabetes. J Clin Lab Anal. 2022;36(5):e24430.
    doi pubmed
13. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(7):1911-1930.
    doi pubmed
14. Abdelsalam M, Nagy E, Abdalbary M, Alsayed MA, Ali AAS, Ahmed RM, Alsuliamany ASM, et al. Prevalence and associated factors of vitamin D deficiency in high altitude region in Saudi Arabia: three-year retrospective study. Int J Gen Med. 2023;16:2961-2970.
    doi pubmed
15. Perez-Lopez FR, Chedraui P, Pilz S. Vitamin D supplementation after the menopause. Ther Adv Endocrinol Metab. 2020;11:2042018820931291.
    doi pubmed
16. Motlaghzadeh Y, Sayarifard F, Allahverdi B, Rabbani A, Setoodeh A, Sayarifard A, Abbasi F, et al. Assessment of vitamin D status and response to vitamin D3 in obese and non-obese Iranian children. J Trop Pediatr. 2016;62(4):269-275.
    doi pubmed
17. Yang K, Liu J, Fu S, Tang X, Ma L, Sun W, Niu Y, et al. Vitamin D status and correlation with glucose and lipid metabolism in Gansu Province, China. Diabetes Metab Syndr Obes. 2020;13:1555-1563.
    doi pubmed
18. Radkhah N, Zarezadeh M, Jamilian P, Ostadrahimi A. The effect of vitamin D supplementation on lipid profiles: an umbrella review of meta-analyses. Adv Nutr. 2023;14(6):1479-1498.
    doi pubmed
19. Alkhatatbeh MJ, Amara NA, Abdul-Razzak KK. Association of 25-hydroxyvitamin D with HDL-cholesterol and other cardiovascular risk biomarkers in subjects with non-cardiac chest pain. Lipids Health Dis. 2019;18(1):27.
    doi pubmed
20. Kostecka D, Schneider-Matyka D, Barczak K, Starczewska M, Szkup M, Ustianowski P, Brodowski J, et al. The effect of vitamin D levels on lipid, glucose profiles and depression in perimenopausal women. Eur Rev Med Pharmacol Sci. 2022;26(10):3493-3505.
    doi pubmed

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