Abstract
Background:
Vitamin D3 deficiency, which is associated with several other diseases such as high blood sugar levels, insulin resistance, and the risk of developing metabolic syndrome (MetS) is prevalent all over the world.Objectives:
This study aimed to determine the prevalence of vitamin D3 deficiency and MetS and evaluate their association in patients referred to the central laboratory of Academic Center for Education, Culture, and Research (ACECR) in Mashahd, Iran.Methods:
This cross-sectional study was conducted on 1,214 patients aged 15 - 75 years referred to the central laboratory of ACECR in Mashhad, Iran, in 2018. Participants with MetS were identified using the Adult Treatment Panel III (ATPIII) criteria. Biochemical parameters and vitamin D3 levels were assessed using the Mindray instrument and the high-performance liquid chromatography (HPLC) method, respectively. The subjects were divided into four groups in terms of serum vitamin D3 concentration as follows: Deficient (< 10 ng/mL), insufficient (10 - 30 ng/mL), sufficient (30 - 80 ng/mL), and toxic (80 < ng/mL).Results:
From a total of 1,214 subjects, 15.0% had vitamin D3 deficiency, 53.2% showed insufficiency, 31.1% were normal with sufficient vitamin D3, and 0.7% suffered from vitamin D3 toxicity. Therefore, 437 (49.7%) females and 209 (62.6%) males suffered from vitamin D3 insufficiency. Overall, 27.6% of females and 33.2% of males had MetS (P < 0.05). Subjects with and without MetS showed no significant difference in serum levels of vitamin D3 (P = 0.608). In addition, there was a significant direct correlation between vitamin D3 levels and systolic blood pressure (SBP) in the group with MetS.Conclusions:
A high proportion of subjects had MetS and insufficient vitamin D3 levels. There were no significant differences between the serum vitamin D3 levels in participants with and without MetS.Keywords
Metabolic Syndrome Deficiency Insufficiency Vitamin D3 Prevalence
1. Background
Vitamin D3 deficiency is widespread worldwide and is increasingly growing in the elderly (1). Vitamin D3 is a lipophilic hormone with an essential role in calcium and phosphorus homeostasis (2-5). Serum vitamin D3 level of 30 - 80 ng/mL is considered as normal, 10 - 30 ng/mL as insufficient, < 10 ng/mL as deficient, and > 80 ng/mL as toxic (1).
In healthy adults, high vitamin D3 is linked with reduced prevalence of metabolic syndrome (MetS), dyslipidemia, abdominal obesity, and hyperglycemia (6-8). Therefore, people with lower vitamin D3 levels due to vitamin D3 deficiency show high blood sugar and insulin resistance. They are also at risk of developing metabolic disorders (1). Many studies found an association between vitamin D3 levels and the risk of cardiovascular diseases (9, 10), diabetes (11, 12), hypertension (13), dyslipidemia (1), obesity, and glucose intolerance. In addition, several studies suggested a correlation between vitamin D3 deficiency and MetS (6, 14, 15). Moreover, vitamin D3 deficiency appears to reduce the levels of intracellular calcium and insulin secretion, which results in abnormal beta-cell function and glucose tolerance impairment (16).
Iran is a country with high prevalence of vitamin D3 deficiency, so that it is estimated that nearly 70% of the Iranian population is deficient in vitamin D3 (17). Today, vitamin D3 deficiency has been recognized as a factor in changes in the metabolic function of many cells, including pancreatic cells (18, 19), and people suffering from MetS have the lowest levels of vitamin D3 (20). Clinical and empirical evidence suggests that serum vitamin D3 levels may be inversely associated with several cancers, type II diabetes, MetS, and cardiovascular diseases (19, 21).
While Strange et al. found a link between vitamin D3 deficiency and MetS and its components (risk factors), Bonakdaran et al. showed the lack of a significant correlation between vitamin D3 deficiency and MetS and its risk factors (21, 22).
It has also been claimed that vitamin D3 deficiency is related to increased systolic and diastolic blood pressures (SBP and DBP), as well as higher blood glucose levels. Additionally, vitamin D3 deficiency in women has been shown to be associated with body mass index (BMI) and central obesity, while the correlation between vitamin D3 deficiency and MetS components has not been found to be significant in men (23). Due to the contradictory results regarding the relationship between vitamin D3 and MetS and its components, the existence of the such relationship is still unclear.
In recent years, the analytical performance of immunoassay methods showed highly unstable results. So, liquid chromatography-tandem mass spectrometry (LC-MS/MS) continues to serve as the gold standard to quantitatively determine the vitamin D metabolites in circulation. The results of previous studies showed a good correlation between the high-performance liquid chromatography (HPLC)-UV and the LC-MS/MS methods. The price of an LC-MS/MS device is high; it is also complicated to use and requires expert technicians. These limitations have restricted its use as a routine laboratory method (24).
2. Objectives
So far, few studies have examined the relationship between the level of vitamin D3 and MetS in Mashhad, Iran. To fill this gap, using the HPLC-UV method, we conducted this study to evaluate the relationship between serum vitamin D levels and MetS in patients referred to the central laboratory of Academic Center for Education, Culture, and Research (ACECR) in Mashhad, Iran in 2018.
3. Methods
3.1. Study Population and Design
This cross-sectional study included 1,214 patients referred to the central laboratory of ACECR in Mashhad, Iran, in 2018. The inclusion criteria were age range of 15 - 75 years and having a history of MetS according to the Adult Treatment Panel III (ATPIII) criteria (25). The exclusion criteria included suffering from systemic diseases, pregnancy, lactation, taking anti-dyslipidemia, anti-hypertensive, anti-diabetic drugs, and nutritional supplements during the study. Accordingly, 4 patients were excluded.
All participants were asked to complete a questionnaire that collected information on sociodemographic status, medical history, employment status, smoking habit, amount of daily exercise, and nutrition. The questionnaire was then reviewed by experienced and trained interviewers.
Body mass index, waist circumference (WC), height, and weight of all the subjects were measured using standard protocols. Systolic and diastolic blood pressures were measured using a standard sphygmomanometer on the left arm following a 15-min rest in a sedentary position.
This study was conducted on subjects diagnosed with MetS based on the ATPIII guideline, which is defined according to abdominal obesity (an abdominal circumference of over 102 cm for men and over 88 cm for women) as a mandatory component for the diagnosis of MetS. Moreover, the ATPIII requires at least 2 of the following four features: High triglyceride (150 mg/dL or more), low HDL-c (less than 40 mg/dL in men and less than 50 mg/dL in women), high blood pressure (85/130 mmHg or higher), and high blood sugar (100 mg/dL or higher).
After measuring 25-hydroxyvitamin D (25 (OH) D3), the subjects were divided into 4 groups according to their level: Normal (30 - 80 ng/mL), insufficient (10 - 30 ng/mL), deficient (< 10 ng/mL), and toxic (> 80 ng/mL).
3.2. Blood Sampling
Blood samples were collected into plain plastic tubes in the morning after 12 - 14 hours of fasting, and the hemolyzed samples were excluded from the analysis. Separation of serum from blood samples was done by centrifuging at 4000 g for 15 minutes.
3.3. Measurements of Biochemical Parameters
Serum fasting blood sugar (FBS) and lipid profile were assessed using the Clinical Chemistry Analyzer (Mindray BS800M, China), and 25 (OH) D3 levels were measured using the HPLC method (RIGOL L-3000, China and Agilent, USA). Chromatography was performed with a mobile phase of methanol: water (95: 5 V/V) in Rigol and acetonitrile: methanol (87: 13 V/V) in Agilent and a column temperature of 40°C.
3.4. Statistical Analysis
The statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS) software version 24. The Kolmogorov-Smirnov test was used to assess the normal distribution of the variables. The quantitative data was presented as mean ± standard division (SD) (for variables with normal distribution) or median and interquartile range (for variables without normal distribution). A P value < 0.05 was considered statistically significant. The chi-square and Fisher’s exact tests were also employed to compare the relationship between vitamin D3 and MetS, as well as the associated risk factors in the groups.
4. Results
During the study period, a total of 1,214 subjects were referred to the central laboratory of ACECR in Mashhad, Iran. The patients’ demographics are shown in Table 1. The subjects were classified into the following groups based on serum vitamin D3 levels: Deficient (< 10 ng/mL), insufficient (10 - 30 ng/mL), sufficient (30 - 80 ng/mL), and toxic (> 80 ng/mL). As shown in Figure 1, 15.0% of the subjects had deficiency, 53.2% had insufficiency, 31.1% were normal with sufficient vitamin D3 levels, and 0.7% suffered from toxicity (a high serum level of vitamin D3). In addition to classifying the subjects based on their vitamin D3 serum levels, the patients were divided into groups according to the MetS status. Furthermore, the relationship between these conditions and gender was separately assessed (Tables 2 and 3). Among the study population, 243 females and 111 males had MetS aside from their vitamin D3 status.
Demographic Results of Patients
| Variables (n = 1214) | Minimum | Maximum | Mean ± SD |
|---|---|---|---|
| Age | 15 | 75 | 41.17 ± 14.04 |
| SBP (mmHg) | 8.0 | 20.0 | 11.84 ± 1.63 |
| DBP (mmHg) | 4.0 | 12.0 | 7.41 ± 1.09 |
| WC (cm) | 44 | 147 | 89.45 ± 11.97 |
| BMI (kg/m2) | 15.24 | 57.44 | 27.56 ± 5.24 |
| Height (cm) | 134.0 | 198.0 | 162.55 ± 9.79 |
| Weight (kg) | 40.80 | 143.0 | 72.72 ± 14.69 |
Distribution of different levels of vitamin D3 (25-hydroxyvitamin D (25 (OH) D)) in study population
| Variables | Vitamin D3 (25 (OH) D) | |||
|---|---|---|---|---|
| Deficiency (< 10 ng/mL) | Insufficiency (10 - 30 ng/mL) | Sufficiency (30 - 80 ng/mL) | Toxic (> 80 ng/mL) | |
| Sex | ||||
| Female | 153 (17.4) | 437 (49.7) | 283 (32.2) | 7 (0.8) |
| Male | 29 (8.7) | 209 (62.6) | 94 (28.1) | 2 (0.6) |
| Total | 182 (15.0) | 646 (53.2) | 377 (31.1) | 9 (0.7) |
| Variables | Metabolic Syndrome | Non-metabolic Syndrome | P Value b |
|---|---|---|---|
| Sex | 0.054 | ||
| Female | 243 (27.6) | 637 (72.4) | |
| Male | 111 (33.2) | 223 (66.8) | |
| Total | 354 (29.2) | 860 (70.8) |
As shown in Table 4, subjects in the two groups of MetS and non-MetS did not have a significant difference in serum levels of vitamin D3 (P = 0.608). Furthermore, population-based data was used to characterize the serum metabolite profile associated with vitamin D3 levels in the total population (Table 5). Next, the situation was evaluated in the group with MetS. The relationship between serum vitamin D3 levels and the risk factors of MetS with serum metabolites was also assessed. According to Table 5, there was a significant direct correlation between vitamin D3 levels and SBP in the group with MetS, but there was no significant association between serum vitamin D3 and other risk factors of MetS.
| Variables | Vitamin D3 (25 (OH) D) | |||
|---|---|---|---|---|
| Deficiency (< 10 ng/mL) | Insufficiency (10 - 30 ng/mL) | Sufficiency (30 - 80 ng/mL) | Toxic (> 80 ng/mL) | |
| Non-metabolic syndrome | 135 (15.7) | 458 (53.3) | 260 (30.2) | 7 (0.8) |
| Metabolic syndrome | 47 (13.3) | 188 (53.1) | 117 (33.1) | 2 (0.6) |
| Total | 182 (15.0) | 646 (53.2) | 377 (31.1) | 9 (0.7) |
Correlation Between Metabolic Syndrome Risk Factors and Serum Vitamin D3 Levels in 4 Groups of Serum Vitamin D3 and Subjects with Metabolic Syndrome
| Variables | Total Correlation | ||||
|---|---|---|---|---|---|
| Serum Vitamin D3 (25 (OH) D) in Total Population | Serum Vitamin D3 (25 (OH) D) in Subjects with Metabolic Syndrome | ||||
| Deficiency (< 10 ng/mL) | Insufficiency (10 - 30 ng/mL) | Sufficiency (30 - 80 ng/mL) | Toxic (> 80 ng/mL) | ||
| FBS | -0.096 | 0.020 | -0.042 | 0.242 | 0.033 |
| TG | 0.021 | -0.012 | -0.059 | -0.044 | -0.48 |
| Chol | 0.076 | 0.009 | 0.021 | 0.062 | 0.093 |
| HDL | 0.006 | -0.048 | 0.073 | 0.342 | 0.037 |
| LDL | 0.044 | 0.003 | 0.020 | 0.028 | 0.057 |
| Ca | -0.026 | -0.011 | 0.037 | 0.089 | 0.014 |
| P | 0. 122 | -0.021 | 0.027 | 0.079 | -0.057 |
| SBP | 0.049 | 0.023 | 0.030 | 0.637 | 0.131 a |
| DBP | -0.010 | -0.018 | -0.018 | -0.597 | 0.57 |
| WC | -0.51 | -0.011 | -0.050 | -0.286 | -0.051 |
| BMI | -0.032 | 0.035 | -0.024 | -0.461 | 0.059 |
5. Discussion
This study aimed to determine the prevalence of vitamin D3 deficiency and MetS and to evaluate the association between them. A high proportion of our subjects had abnormally low vitamin D3 levels. Also, 68.2% of the population suffered from insufficient vitamin D3 levels (< 30 ng/mL). In agreement with this study, several previous studies revealed the high prevalence of vitamin D3 deficiency in the Iranian population (26-30), which is due to various factors like the way of dressing, having unhealthy dietary habits, and overuse of cosmetics and sunscreens (31-33). The high degree of discrepancy in various studies may be ascribed to the following factors: Different study populations, ethnic diversity in vitamin D3 metabolism, genetic and epigenetic factors, the season in which the studies were performed, as well as the methods used for determining vitamin D3 levels (34-37). In our subjects, the prevalence of vitamin D3 insufficiency in males was higher than that of females, partly due to the fact that a growing number of women are taking vitamin D3 supplements, which is consistent with the results of previous studies (38). In contrast, some other studies showed that women are more vitamin D3 deficient than men (39, 40).
In our study, the prevalence of MetS was 29.2%. The results of a study by Kalan Farmanfarma et al. showed that approximately one-third of the adult Iranian population has MetS (41). It has also been suggested that MetS can be influenced by different factors such as female gender, aging, and being overweight or obese (42). In this study, there was no significant difference in serum vitamin D3 levels between participants with and without MetS. Similar to this study, Bonakdaran et al. found no considerable difference in serum vitamin D3 concentrations between individuals with or without MetS (22). Kaseb et al. found no significant association between MetS and vitamin D3 deficiency among overweight and obese adults (43). Liu et al. stated that neither total nor supplemental vitamin D3 was significantly related to MetS (5). Reis et al. studied participants aged 44 - 96 years and found no correlation between vitamin D3 and MetS in either sex (44). Several studies support the hypothesis that adequate blood levels of vitamin D3 improve MetS (45, 46). Rafraf et al. showed that subjects with MetS had significantly lower vitamin D3 levels than those without MetS (47). Esteghamati et al. found that metabolically healthy obese subjects had higher serum vitamin D3 levels than those with metabolically unhealthy obesity (48). Ford et al. showed that the concentration of vitamin D3 was significantly lower among patients with MetS than those without MetS (15). Chiu et al. studied healthy glucose-tolerant subjects and showed that those with hypovitaminosis D3 had a higher prevalence of MetS components than subjects without hypovitaminosis D3 (49). Botella-Carretero et al. reviewed morbidly-obese patients and showed that vitamin D3 deficiency was more prevalent in morbidly-obese patients that suffered from MetS compared with those who did not meet the criteria for this syndrome (50). Lu et al. found that low vitamin D3 level was significantly associated with an increased risk of MetS (51).
The relationship between serum vitamin D3 and MetS risk factors is shown in Table 5. According to our result, there was a significant direct correlation between serum Vitamin D3 levels with SBP in subject with MetS, but no significant associations were found between serum vitamin D3 and other risk factors of MetS. Contrary to this result, Rafraf et al. showed that serum vitamin D3 was inversely associated with FBG, and no significant associations were found between serum vitamin D3 and other risk factors of MetS (47). Furthermore, Chiu et al. found a negative correlation between vitamin D3 concentration and BMI, total and LDL cholesterols, and 60-, 90-, and 120-min post-challenge plasma glucose concentrations (49). Among the components of MetS, a significant inverse correlation was found for quintiles of vitamin D3 concentration with abdominal adiposity, hypertriglyceridemia, and hyperglycemia (15). In another study, serum vitamin D3 level was negatively and significantly associated with WC, SBP, and DBP, but positively associated with BMI (26).
This study had several limitations. First, the cross-sectional nature of the data impedes the ability to infer the causation between vitamin D3 and the risk factors of MetS. Second, a relatively small sample size was another limitation of this study. Therefore, researchers can conduct more studies with larger sample sizes.
5.1. Conclusions
According to the results of this study, a high ratio of our subjects suffered from MetS (29.2%) and insufficient vitamin D3 levels (68.2%). Also, there was no significant difference between serum vitamin D3 levels in participants with MetS and those without MetS. Future studies with a long-term longitudinal design are needed to explain the cause-and-effect relationship between vitamin D3 status and MetS.
Acknowledgements
References
-
1.
Jang HB, Lee HJ, Park JY, Kang JH, Song J. Association between serum vitamin d and metabolic risk factors in korean schoolgirls. Osong Public Health Res Perspect. 2013;4(4):179-86. [PubMed ID: 24159553]. [PubMed Central ID: PMC3767105]. https://doi.org/10.1016/j.phrp.2013.06.004.
-
2.
Pinelli NR, Jaber LA, Brown MB, Herman WH. Serum 25-hydroxy vitamin d and insulin resistance, metabolic syndrome, and glucose intolerance among Arab Americans. Diabetes Care. 2010;33(6):1373-5. [PubMed ID: 20332348]. [PubMed Central ID: PMC2875457]. https://doi.org/10.2337/dc09-2199.
-
3.
Chowdhury TA, Boucher BJ, Hitman GA. Vitamin D and type 2 diabetes: Is there a link? Prim Care Diabetes. 2009;3(2):115-6. [PubMed ID: 19395331]. https://doi.org/10.1016/j.pcd.2009.03.004.
-
4.
Boucher BJ, Mannan N, Noonan K, Hales CN, Evans SJ. Glucose intolerance and impairment of insulin secretion in relation to vitamin D deficiency in east London Asians. Diabetologia. 1995;38(10):1239-45. [PubMed ID: 8690178]. https://doi.org/10.1007/BF00422375.
-
5.
Liu S, Song Y, Ford ES, Manson JE, Buring JE, Ridker PM. Dietary calcium, vitamin D, and the prevalence of metabolic syndrome in middle-aged and older U.S. women. Diabetes Care. 2005;28(12):2926-32. [PubMed ID: 16306556]. https://doi.org/10.2337/diacare.28.12.2926.
-
6.
Verrusio W, Andreozzi P, Renzi A, Musumeci M, Gueli N, Cacciafesta M. Association between serum vitamin D and metabolic syndrome in middle-aged and older adults and role of supplementation therapy with vitamin D. Ann Ist Super Sanita. 2017;53(1):54-9. [PubMed ID: 28361806]. https://doi.org/10.4415/ANN_17_01_11.
-
7.
Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357(3):266-81. [PubMed ID: 17634462]. https://doi.org/10.1056/NEJMra070553.
-
8.
Vitezova A, Zillikens MC, van Herpt TT, Sijbrands EJ, Hofman A, Uitterlinden AG, et al. Vitamin D status and metabolic syndrome in the elderly: the Rotterdam Study. Eur J Endocrinol. 2015;172(3):327-35. [PubMed ID: 25468955]. https://doi.org/10.1530/EJE-14-0580.
-
9.
Lann D, LeRoith D. Insulin resistance as the underlying cause for the metabolic syndrome. Med Clin North Am. 2007;91(6):1063-77. viii. [PubMed ID: 17964909]. https://doi.org/10.1016/j.mcna.2007.06.012.
-
10.
Danik JS, Manson JE. Vitamin d and cardiovascular disease. Curr Treat Options Cardiovasc Med. 2012;14(4):414-24. [PubMed ID: 22689009]. [PubMed Central ID: PMC3449318]. https://doi.org/10.1007/s11936-012-0183-8.
-
11.
Thaman R, Arora G. Metabolic Syndrome: Definition and Pathophysiology and #8211; the discussion goes on!. J Physiol Pharmacol Adv. 2013;3(3). https://doi.org/10.5455/jppa.20130317071355.
-
12.
Wang H, Zhang H, Jia Y, Zhang Z, Craig R, Wang X, et al. Adiponectin receptor 1 gene (ADIPOR1) as a candidate for type 2 diabetes and insulin resistance. Diabetes. 2004;53(8):2132-6. [PubMed ID: 15277397]. https://doi.org/10.2337/diabetes.53.8.2132.
-
13.
Eckel RH, Grundy SM, Zimmet PZ. The metabolic syndrome. Lancet. 2005;365(9468):1415-28. [PubMed ID: 15836891]. https://doi.org/10.1016/S0140-6736(05)66378-7.
-
14.
Brenner DR, Arora P, Garcia-Bailo B, Wolever TM, Morrison H, El-Sohemy A, et al. Plasma vitamin D levels and risk of metabolic syndrome in Canadians. Clin Invest Med. 2011;34(6). E377. [PubMed ID: 22129928]. https://doi.org/10.25011/cim.v34i6.15899.
-
15.
Ford ES, Ajani UA, McGuire LC, Liu S. Concentrations of serum vitamin D and the metabolic syndrome among U.S. adults. Diabetes Care. 2005;28(5):1228-30. [PubMed ID: 15855599]. https://doi.org/10.2337/diacare.28.5.1228.
-
16.
Volek JS, Fernandez ML, Feinman RD, Phinney SD. Dietary carbohydrate restriction induces a unique metabolic state positively affecting atherogenic dyslipidemia, fatty acid partitioning, and metabolic syndrome. Prog Lipid Res. 2008;47(5):307-18. [PubMed ID: 18396172]. https://doi.org/10.1016/j.plipres.2008.02.003.
-
17.
Moradzadeh K, Keshtkar A, Hossein NA, Rajabian R, Nabipour I, Omrani G, et al. [Normal values of vitamin D and prevalence of vitamin D deficiency among Iranian population]. Sci J Kurdistan Univ Medical Sci. 2006;10(4):33-43. Persian.
-
18.
McGill AT, Stewart JM, Lithander FE, Strik CM, Poppitt SD. Relationships of low serum vitamin D3 with anthropometry and markers of the metabolic syndrome and diabetes in overweight and obesity. Nutr J. 2008;7:4. [PubMed ID: 18226257]. [PubMed Central ID: PMC2265738]. https://doi.org/10.1186/1475-2891-7-4.
-
19.
Targher G, Bertolini L, Padovani R, Zenari L, Scala L, Cigolini M, et al. Serum 25-hydroxyvitamin D3 concentrations and carotid artery intima-media thickness among type 2 diabetic patients. Clin Endocrinol (Oxf). 2006;65(5):593-7. [PubMed ID: 17054459]. https://doi.org/10.1111/j.1365-2265.2006.02633.x.
-
20.
Talaei A, Mashayekhi N. [Correlation between metabolic syndrome and serum concentration of vitamin 25 (OH) D]. Iran South Med J. 2015;17(6):1188-94. Persian.
-
21.
Strange RC, Shipman KE, Ramachandran S. Metabolic syndrome: A review of the role of vitamin D in mediating susceptibility and outcome. World J Diabetes. 2015;6(7):896-911. [PubMed ID: 26185598]. [PubMed Central ID: PMC4499524]. https://doi.org/10.4239/wjd.v6.i7.896.
-
22.
Bonakdaran S, Fakhraee F, Karimian MS, Mirhafez SR, Rokni H, Mohebati M, et al. Association between serum 25-hydroxyvitamin D concentrations and prevalence of metabolic syndrome. Adv Med Sci. 2016;61(2):219-23. [PubMed ID: 26907695]. https://doi.org/10.1016/j.advms.2016.01.002.
-
23.
Chiang JM, Stanczyk FZ, Kanaya AM. Vitamin D Levels, Body Composition, and Metabolic Factors in Asian Indians: Results from the Metabolic Syndrome and Atherosclerosis in South Asians Living in America Pilot Study. Ann Nutr Metab. 2018;72(3):223-30. [PubMed ID: 29518767]. [PubMed Central ID: PMC5907927]. https://doi.org/10.1159/000487272.
-
24.
Altieri B, Cavalier E, Bhattoa HP, Perez-Lopez FR, Lopez-Baena MT, Perez-Roncero GR, et al. Vitamin D testing: advantages and limits of the current assays. Eur J Clin Nutr. 2020;74(2):231-47. [PubMed ID: 31907366]. https://doi.org/10.1038/s41430-019-0553-3.
-
25.
National Cholesterol Education Program Expert Panel on Detection Evaluation Treatment of High Blood Cholesterol in Adults. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002;106(25):3143-421. [PubMed ID: 12485966].
-
26.
Mellati AA, Sharifi F, Faghihzade S, Mousaviviri SA, Chiti H, Kazemi SA. Vitamin D status and its associations with components of metabolic syndrome in healthy children. J Pediatr Endocrinol Metab. 2015;28(5-6):641-8. [PubMed ID: 25928755]. https://doi.org/10.1515/jpem-2013-0495.
-
27.
Akhlaghi M, Kamali M, Dastsouz F. Both Low and Upper Normal Levels of 25-Hydroxy Vitamin D Relates to Risk Factors of Metabolic Syndrome and Cardiovascular Diseases. J Health Sci Surveillance Sys. 2016;4(4):181-8.
-
28.
Mansouri M, Abasi R, Nasiri M, Sharifi F, Vesaly S, Sadeghi O, et al. Association of vitamin D status with metabolic syndrome and its components: A cross-sectional study in a population of high educated Iranian adults. Diabetes Metab Syndr. 2018;12(3):393-8. [PubMed ID: 29398635]. https://doi.org/10.1016/j.dsx.2018.01.007.
-
29.
Afkhami-Ardekani O, Afkhami-Ardekani A, Namiranian N, Afkhami-Ardekani M, Askari M. Prevalence and predictors of vitamin D insufficiency in adult population of yazd - The sun province in center of Iran. Diabetes Metab Syndr. 2019;13(5):2843-7. [PubMed ID: 31425945]. https://doi.org/10.1016/j.dsx.2019.07.050.
-
30.
Esmaeili SA, Mohammadian S, Radbakhsh S, Momtazi-Borojeni AA, Kheirmand Parizi P, Atabati H, et al. Evaluation of vitamin D3 deficiency: A population-based study in northeastern Iran. J Cell Biochem. 2019;120(6):10337-41. [PubMed ID: 30556194]. https://doi.org/10.1002/jcb.28317.
-
31.
Hagenau T, Vest R, Gissel TN, Poulsen CS, Erlandsen M, Mosekilde L, et al. Global vitamin D levels in relation to age, gender, skin pigmentation and latitude: an ecologic meta-regression analysis. Osteoporos Int. 2009;20(1):133-40. [PubMed ID: 18458986]. https://doi.org/10.1007/s00198-008-0626-y.
-
32.
Alipour S, Saberi A, Seifollahi A, Shirzad N, Hosseini L. Risk factors and prevalence of vitamin d deficiency among Iranian women attending two university hospitals. Iran Red Crescent Med J. 2014;16(10). e15461. [PubMed ID: 25763193]. [PubMed Central ID: PMC4329745]. https://doi.org/10.5812/ircmj.15461.
-
33.
Faghih S, Abdolahzadeh M, Mohammadi M, Hasanzadeh J. Prevalence of vitamin d deficiency and its related factors among university students in shiraz, iran. Int J Prev Med. 2014;5(6):796-9. [PubMed ID: 25013702]. [PubMed Central ID: PMC4085935].
-
34.
Reis JP, von Muhlen D, Miller E3, Michos ED, Appel LJ. Vitamin D status and cardiometabolic risk factors in the United States adolescent population. Pediatrics. 2009;124(3):e371-9. [PubMed ID: 19661053]. [PubMed Central ID: PMC4222068]. https://doi.org/10.1542/peds.2009-0213.
-
35.
Saintonge S, Bang H, Gerber LM. Implications of a new definition of vitamin D deficiency in a multiracial us adolescent population: the National Health and Nutrition Examination Survey III. Pediatrics. 2009;123(3):797-803. [PubMed ID: 19255005]. https://doi.org/10.1542/peds.2008-1195.
-
36.
Barati M, Alizadeh-Sani M, Safari H, Taghizadeh Jazdani S, Taghizadeh Jazdani R. Associations of Environmental Factors and Prevalence of Vitamin D Deficiency in Iran. J Nutrition Fasting Health. 2018;6(4):182-90.
-
37.
Bahrami A, Sadeghnia HR, Tabatabaeizadeh SA, Bahrami-Taghanaki H, Behboodi N, Esmaeili H, et al. Genetic and epigenetic factors influencing vitamin D status. J Cell Physiol. 2018;233(5):4033-43. [PubMed ID: 29030989]. https://doi.org/10.1002/jcp.26216.
-
38.
Heshmat R, Mohammad K, Majdzadeh S, Forouzanfar M, Bahrami A, Ranjbar Omrani G, et al. Vitamin D deficiency in Iran: A multi-center study among different urban areas. Iranian J Publ Health. 2008;37(1):72-8.
-
39.
Rahmati S, Yadegarazadi A, Beigom B, Rabiei FF, Azami M, Borji M, et al. [The frequency of vitamin d deficiency among referred to clinical laboratories in Eyvan city during 2015 and 2016-Ilam province, Iran]. Journal of Shahid Sadoughi University of Medical Sciences and Health Services. 2016;24(3):261-8. Persian.
-
40.
Shohani M, Mansouri A, Azami M, Soleymani A, Badfar G. The study of vitamin D Status in population referred to clinical laboratories in ilam, west of Iran. Crescent J Med Biol Sci. 2018;5(2):115-8.
-
41.
Kalan Farmanfarma K, Kaykhaei MA, Adineh HA, Mohammadi M, Dabiri S, Ansari-Moghaddam A. Prevalence of metabolic syndrome in Iran: A meta-analysis of 69 studies. Diabetes Metab Syndr. 2019;13(1):792-9. [PubMed ID: 30641809]. https://doi.org/10.1016/j.dsx.2018.11.055.
-
42.
Ebrahimi H, Emamian MH, Shariati M, Hashemi H, Fotouhi A. Metabolic syndrome and its risk factors among middle aged population of Iran, a population based study. Diabetes Metab Syndr. 2016;10(1):19-22. [PubMed ID: 26341930]. https://doi.org/10.1016/j.dsx.2015.08.009.
-
43.
Kaseb F, Haghighyfard K, Salami MS, Ghadiri-Anari A. Relationship Between Vitamin D Deficiency and Markers of Metabolic Syndrome Among Overweight and Obese Adults. Acta Med Iran. 2017;55(6):399-403. [PubMed ID: 28843242].
-
44.
Reis JP, von Muhlen D, Kritz-Silverstein D, Wingard DL, Barrett-Connor E. Vitamin D, parathyroid hormone levels, and the prevalence of metabolic syndrome in community-dwelling older adults. Diabetes Care. 2007;30(6):1549-55. [PubMed ID: 17351276]. https://doi.org/10.2337/dc06-2438.
-
45.
Khan H, Kunutsor S, Franco OH, Chowdhury R. Vitamin D, type 2 diabetes and other metabolic outcomes: a systematic review and meta-analysis of prospective studies. Proc Nutr Soc. 2013;72(1):89-97. [PubMed ID: 23107484]. https://doi.org/10.1017/S0029665112002765.
-
46.
Belenchia AM, Tosh AK, Hillman LS, Peterson CA. Correcting vitamin D insufficiency improves insulin sensitivity in obese adolescents: a randomized controlled trial. Am J Clin Nutr. 2013;97(4):774-81. [PubMed ID: 23407306]. https://doi.org/10.3945/ajcn.112.050013.
-
47.
Rafraf M, Hasanabad SK, Jafarabadi MA. Vitamin D status and its relationship with metabolic syndrome risk factors among adolescent girls in Boukan, Iran. Public Health Nutr. 2014;17(4):803-9. [PubMed ID: 24477119]. https://doi.org/10.1017/S1368980013003340.
-
48.
Esteghamati A, Aryan Z, Esteghamati A, Nakhjavani M. Differences in vitamin D concentration between metabolically healthy and unhealthy obese adults: associations with inflammatory and cardiometabolic markers in 4391 subjects. Diabetes Metab. 2014;40(5):347-55. [PubMed ID: 24811744]. https://doi.org/10.1016/j.diabet.2014.02.007.
-
49.
Chiu KC, Chu A, Go VL, Saad MF. Hypovitaminosis D is associated with insulin resistance and beta cell dysfunction. Am J Clin Nutr. 2004;79(5):820-5. [PubMed ID: 15113720]. https://doi.org/10.1093/ajcn/79.5.820.
-
50.
Botella-Carretero JI, Alvarez-Blasco F, Villafruela JJ, Balsa JA, Vazquez C, Escobar-Morreale HF. Vitamin D deficiency is associated with the metabolic syndrome in morbid obesity. Clin Nutr. 2007;26(5):573-80. [PubMed ID: 17624643]. https://doi.org/10.1016/j.clnu.2007.05.009.
-
51.
Lu L, Yu Z, Pan A, Hu FB, Franco OH, Li H, et al. Plasma 25-hydroxyvitamin D concentration and metabolic syndrome among middle-aged and elderly Chinese individuals. Diabetes Care. 2009;32(7):1278-83. [PubMed ID: 19366976]. [PubMed Central ID: PMC2699709]. https://doi.org/10.2337/dc09-0209.