Clinical Rheumatology

, Volume 31, Issue 8, pp 1197–1203 | Cite as

Association between metabolic syndrome, BMI, and serum vitamin D concentrations in rheumatoid arthritis

  • Ladan Goshayeshi
  • HamidReza Saber
  • Maryam Sahebari
  • Zahra Rezaieyazdi
  • Houshang Rafatpanah
  • Habibollah Esmaily
  • Lena Goshayeshi
Original Article

Abstract

Rheumatoid arthritis (RA) is the most common autoimmune arthritis. The impact of chronic inflammation on atherosclerosis and insulin resistance has been observed in several autoimmune diseases. On the other hand, metabolic syndrome (MetS); a cluster of traditional risk factors for atherosclerosis and diabetes seems to be prevalent in RA patients. It is reasonable to think that protective factors against inflammation can protect patients against atherosclerosis and diabetes, too. Vitamin D (Vit D), a novel immunomodulator, is recently considered to play a protective role against cardiovascular diseases, insulin resistance, and obesity. This cross-sectional study was designed to evaluate the impact of serum Vit D on MetS and body mass index (BMI). One hundred twenty RA patients were enrolled. MetS was assessed according to Adult Treatment Panel III criteria. All patients with known confounders influencing Vit D serum levels were excluded. Serum value of 25-hydroxyvitamin D (25(OH)D) was measured using a commercial ELISA kit. Data were analyzed by SPSS software. A logistic regression analysis stated that prednisolone dosage [p = 0.028, β = 0.177, odds ratio (OR) = 1.194, confidence interval (CI, 1.09–1.32)], age [p = 0.002, β = 0.146, OR = 1.57, CI (1.05–1.27)] and Vit D serum levels [p = 0.049, β = −3.766, OR = 0.023, CI (0.001–0.978)] are all significant predictors of MetS occurrence in RA patients. It was shown that 25(OH)D is a protective factor against MetS. It was also shown that there is a negative correlation between BMI and 25(OH)D serum levels (P = 0.037, rs = −0.266). In summary, this study suggested that 25(OH)D plays a protective role against MetS in RA patients. However, this cross-sectional study did not permit a power calculation on the causal relationship between Vit D and metabolic syndrome. On the other hand, Vit D has a negative correlation with BMI in these patients.

Keywords

BMI Body mass index Metabolic syndrome Rheumatoid arthritis Vitamin D 

Introduction

Rheumatoid arthritis (RA) is the most common systemic autoimmune arthritis that affects 0.5–1 % of the population [1]. RA is associated with increased morbidity and mortality [2, 3]. Emerging epidemiological evidence suggests that cardiovascular diseases (CVDs) account for about half of all deaths in this population.

Metabolic syndrome is a cluster of traditional risk factors that include hyperglycemia, hypertriglyceridemia, low level of high-density lipoprotein cholesterol (HDL-C), hypertension, and central obesity [4], which is considered as a strong predictor for diabetes and CVDs [5, 6].

Recent population-based, cross-sectional studies propose that vitamin D can contribute to an increased risk of cardiovascular diseases and metabolic syndrome (MetS) [7, 8, 9, 10]. Vitamin D (Vit D) concentrations are also suggested to be associated with obesity [11, 12]. However, in the setting of RA, the clinical consequences of vitamin D deficiency remain a matter of debate [13, 14, 15]. It is supposed that vitamin D deficiency is associated with autoimmune diseases [13, 14, 15]. However, the correlation among vitamin D, autoimmune diseases, and metabolic syndrome is not clearly understood. In particular, the association between Vit D deficiency and MetS among RA patients is not known.

In this study, we aimed to determine whether a low serum concentration of 25-hydroxyvitamin D (25(OH)D) is associated with MetS among RA patients or not. We assumed that a low serum 25(OH)D level is an independent risk factor for MetS in RA. Therefore, it was hypothesized that RA patients with lower serum concentrations of 25(OH)D would be more likely to develop MetS compared with patients with higher levels of Vit D. In other words, investigating the correlation between serum values of 25(OH)D and MetS and its components like hypertension, diabetes, and hyperlipidemia is the main goal of this study. Affirmation of this correlation would distinguish hypovitaminosis D as a potentially modifiable diabetes and cardiovascular risk factor among RA patients.

Materials and methods

Patients

One hundred and twenty RA patients including 106 (88.3 %) females and 14 (11.7 %) males with different stages of disease activity were enrolled in this cross-sectional study. The study was conducted in Mashhad city, Iran, which is located at 36.20° latitude and 59.35° east longitudes. All RA patients fulfilled the 1987 American College of Rheumatology revised criteria for RA. Every consecutive patient who did not have exclusion criteria of this study was recruited from clinical RA cohorts, local rheumatologists, and rheumatology clinics of two of our university hospitals between January 2009 and March 2010. The exclusion criteria were considered as follows: use of vitamin D injectable compounds or vitamin D pearls (more than physiologic doses) in the previous 6 months, anticonvulsive therapy and a prior history or clinical features of medical conditions including intestinal surgery, malignancies, parathyroid disorders, recent or chronic diarrhea, malabsorption, renal insufficiency, liver failure, and infections. All patients in this study were treated with daily doses of hydroxychloroquine 6 mg/kg and calcium–Vit D tablets including 1,000 mg calcium and 800 units of vitamin D (physiologic doses).

At baseline, volunteers' demographic, anthropometric, clinical, and laboratory data were collected for evaluation of MetS. MetS were defined by the presence of any three of the following five characteristics according to the National Cholesterol Education Program's Adult Treatment Panel III report: abdominal obesity based on waist circumference (>102 cm in men and >88 cm in women), triglycerides at least 150 mg/dl, high-density lipoprotein (HDL) below 40 mg/dl for men and 50 mg/dl for women, blood pressure at least 130/85 mmHg, and fasting glucose at least 110 mg/dl (or who are undertreatment for hyperlipidemia, hypertension, or diabetes) [5]. Vitamin D deficiency is defined as a 25-hydroxyvitamin D serum level of less than 50 nmol per liter. Serum values of 25(OH)D of 51 to 75 nmol per liter is considered as vitamin D insufficiency [16]. According to an epidemiologic study in our country which included Mashhad city (the city in which this study was conducted) another classification was defined: 25(OH)D serum values more than 35 nmol/L is considered sufficient Vit D, 25 < 25(OH)D ≤ 35 nmol/L and 25(OH)D ≤ 25 nmol/L were considered insufficiency and deficiency, respectively[17].

All participants gave an informed written consent prior to participation in this study, which was approved by the Ethic Committee of Mashhad University of Medical Sciences.

Anthropometric measurements

Anthropometric parameters including height, weight, waist circumference, and body mass index (BMI), as well as systolic and diastolic blood pressures were measured for all participants. Height (centimeters) was recorded in all subjects without shoes, and weight (kilograms) was measured for participants in light clothing using electronic weighing scales. Waist (at the level of the umbilicus) and hip (defined as the widest part of the body below the waist) measurements were also taken, and the WHR was computed. BMI was computed using weight in kilograms divided by the square of the height in meter. For measuring blood pressure, the participants remained seated for 15 min and at least two readings of blood pressure were taken.

Biochemical measurements

Fasting blood sugar (FBS), lipid profile including total cholesterol, triglycerides, HDL-C, and low-density lipoprotein cholesterol (LDL-C) were determined for each participant after an overnight fasting. Erythrocyte sedimentation rate (ESR) was measured by Westergren method. After being allowed to clot, the blood was then centrifuged at 2,500 rpm for 15 min at room temperature to obtain serum. Hemolyzed samples were excluded from analysis. Serum was stored at −20 °C prior to analysis. Serum FBS and lipid profile were measured by enzymatic methods. Serum 25(OH)D was measured using a commercial ELISA kit (immunodiagnostic system, UK) in accordance with manufacturer's instruction.

Their assessment also included a structured interview, laboratory tests, review of medical records and smoking habits including cigarette and hookah, and personal or family history of ischemic heart disease.

Statistical analysis

The SPSS software (version 11.5, Chicago, IL, USA) was used for statistical analysis. Kolomogrov–Smirnov test was used to evaluate the normality of data. Values were expressed as mean±SD for normally distributed variables and median with interquartile range (IQR) for non-normally distributed data. Baseline demographics and clinical characteristics were compared between groups using independent samples t test, Mann–Whitney U test, chi-square, and/or Fisher's exact test, as appropriate. Bivariate correlations were assessed using Pearson's and Spearman's correlation coefficients for normally and non-normally distributed data respectively. Variables including Vit D or those of clinical interest in development of MetS were selected for logistic regression analysis of variance. Odds ratios with a 95 % confidence interval were calculated. A P value < 0.05 was considered significant. As Vit D serum values did not have statistically normal distribution, its logarithm was used for computing logistic regression analysis. Potential confounding variables including age, sex, season of Vit D measurement and medications such as methotrexate and prednisolone dosage were evaluated by forward conditional model.

Results

Demographics

One hundred twenty patients (106 women and 14 men) participated in this study. There was no significant difference between RA patients with and without MetS regarding gender and age. Thirteen patients had early RA (less than 6-month history of arthritis). The average age and BMI of our subjects were 45.5 years and 26.8 kg/m2, respectively.

The mean duration of the disease was 5.5 ± 5.2 years. The patients had a mean ESR of 20 (13–37) mm/h, CRP 20 (0–40) mg/L, and rheumatoid factor (RF) 20 (0–40) units/mL. Antibodies to cyclic citrullinated peptides were positive in 70 % and RF was positive in 79 % of sera of this population. Patients' drug history included prednisolone with an average dose of 5.5 ± 3.6 mg/day (108 patients), 6 mg/kg of hydroxychloroquine (all patients) and methotrexate with an average dose of 7.9 ± 5.7 mg per week (90 patients). Besides, 32 patients were being treated with sulfasalazine or azathioprine; six patients were under treatment with rituximab or infliximab in addition to mentioned drugs. All patients received supplementary calcium (1,000 mg/day) and vitamin D (800 U/day). Thirteen patients had early RA (duration of RA less than 6 month). Seven percent of our patients were smoker. The mean disease activity score (DAS28ESR) of patients was 4.45 ± 1.67.

Among 45.2 % of patients who met the definition of MetS, systolic and diastolic blood pressure, fasting blood sugar, cholesterol, triglyceride, weight, and belt were significantly higher compared with patients without metabolic syndrome according to the independent sample t test and Mann–Whitney U test results. Table 1 shows distribution of metabolic components and important patients' information in this study. Seven percent of our patients were smoker, it was not a significant difference between number of smokers in patients with and without MetS (p = 0.39) (chi-square).
Table 1

Demographics of total patients, patients with and without MetS

Demographics and metabolic components

Patients (n = 120)

MetS (n = 54) 45.2 %

No MetS (n = 66) 54.8 %

P value (patents with MetS vs. patients without MetS)

Age (years), mean±SD

45.49 ± 14.21

53.25 ± 9

42.47 ± 14.8

P < 0.001

t = 3.6

Systolic BP (mmHg), median (IQR)

110 (20)

120.50 (30)

110 (22.5)

0.001

z = 3.7

Diastolic BP (mmHg), median (IQR)

70 (10)

80 (9.9)

70 (20)

0.002

z = 3.15

Weight (kg), median (IQR)

65 (16.5)

70 (16)

61.50 (17.5)

0.012

z = 2.5

Belt circumference (cm), median (IQR)

90 (22)

102 (11)

85 (14)

<0.001

z = 4.76

BMI (kg/m2), mean±SD

26.57 ± 4.7

28.74 ± 4.6

25.7 ± 4.5

0.004

t = 2.99

FBS (mg/dL)a, median (IQR)

87,050 (18.75)

97 (30.75)

84.5 (15,075)

0.009

z = 2.6

Triglyceride (mg/dL)a, median (IQR)

107 (116)

159 (164)

90.50 (46.25)

<0.001

z = 3.49

Cholesterol (mg/dL)a, mean±SD

216 ± 180

204.35 ± 178.5

248 ± 185

0.3

t = 1.02

LDL-C (mg/dL)a, mean±SD

115.6 ± 35

122.5 ± 42.8

113.2 ± 31.8

0.29

t = 1.05

HDL-C (mg/dL)a, mean±SD

47.13 ± 12.7

4,522 ± 9.5

47.9 ± 13.9

0.35

t = 0.93

aFBS and lipid profile of patients under treatment whit hypoglycemic or lipid lowering agents were included

The mean serum concentration of 25-hydroxyvitamin D was 57.15 ± 34.96 nmol/L. Forty six percent of patients had vitamin D deficiency (serum values less than 50 nmol/L) and 26 % had vitamin D insufficiency (serum values between 51 and 75 nmol/L).

Association between 25-hydroxyvitamin D levels and metabolic syndrome

In this study, up to 45.2 % of 120 participants met the definition of MetS. Among patients without MetS (54.8 % of patients), 67 % were vitamin D sufficient [25(OH) D ≥ 50 nmol/L].

Metabolic components including FBS, cholesterol subtypes, blood pressure, and waist circumference had no correlation with Vit D serum values. In this study, older patients had higher serum values of Vit D (Table 2).
Table 2

Logistic regression analysis of predictors for MetS occurrence in RA patients

Variables

P value

β

OR

95 % Confidence interval

Age

0.002

0.146

1.157

1.05–1.27

Prednisolone dosage

0.028

0.177

1.194

1.09–1.32

vitD

0.049

−3.766

0.023

0.001–0.978

The Vit D effect on concomitance of MetS with RA was evaluated by logistic regression analysis of variance. Confounding factors including age, gender, season of sampling, and dosage of prednisolone and methotrexate were controlled by the forward conditional method. Statistical analysis showed that gender (p = 0.3), season of sampling (p = 0.46), and methotrexate dosage (p = 0.95) had no effect on this association. A logistic regression analysis revealed that prednisolone dosage, age of patients, and Vit D serum levels were all significant predictors of MetS occurrence in RA patients. It was shown that 25(OH)D is a protective factor against MetS (Table 2). In the presence of other variables, the statistical analysis showed that BMI has no direct influence on MetS. In addition, we found no association between MetS and prednisolone dosage (p = 0.16, t = −1.4).

Association between 25-hydroxyvitamin D levels and BMI

We found an inverse correlation between BMI and 25(OH)D serum levels. A decrease in 25(OH)D serum value was observed in parallel with an increase in BMI level (P = 0.037, rs = −0.266). When patients were categorized into three groups according to Vit D serum values, it was observed that BMI significantly differs among these groups (p = 0.049, one-way analysis of variance (ANOVA)) and patients with 25(OH)D serum values more than 35 nmol/L had significantly lower BMI than those with 25(OH)D serum values less than 25 nmol/L (Table 3 and Fig. 1).
Table 3

distribution of BMI in different 25(OH)D serum values of RA patients

Vitamin D (nmol/L)

12.5 < Vit D ≤ 25

25 < Vit D ≤ 35

Vit D > 35

Group

A

B

C

BMI

33.06 ± 2.12

25.98 ± 3.28

25.9 ± 5.06

P value between three groups: 0.049 one-way ANOVA

P value between group A and B: 0.08 (Tukey test)

P value between group B and C: 0.99 (Tukey test)

P value between group A and C: 0.038 (Tukey test)

Fig. 1

BMI distribution in different vitamin D serum values

Discussion

In this study, we found a high prevalence of Vit D insufficiency among RA patients. Although these patients received physiologic doses of Vit D, the conservative dress code in the country, nutritional Vit D deficiency, which is due to inaccessibility of Vit D-enriched food products in our country and sedentary life styles, which are caused by joint pain and morning stiffness are leading causes of Vit D insufficiency in our patients.

Vit D had a protective role against MetS. Likewise, we observed an inverse correlation between Vit D concentrations and BMI. Several studies suggest that low serum levels of Vit D may be common in RA [18, 19, 20]. Some other studies have observed a higher rate of MetS in RA patients [21, 22]. In a previous study on middle-aged individuals in our population, we did not find a significant difference between MetS among RA patients and age and sex match healthy controls. We found MetS to be more common in normal population (45.2 %) than in RA patients (30.8 %) [23].

Low Vit D status has been associated with an increased risk of MetS. Ford et al. [7] observed that individuals in the lowest quintile of 25(OH)D (<48.4 nmol/L) were twice as likely to contract MetS compared with those in the highest quintile (>96.4 nmol/L). Another recent cross-sectional analysis of 1,654 men and women reported a substantially lower odds ratio (OR) for MetS in the highest quintile of 25(OH)D (median 88.0 nmol/L; OR 0.15) compared with the lowest quintile (median 26.8 nmol/L; OR 0.46)[24]. The mechanisms by which low Vit D could be associated with MetS remain speculative [24]. Several studies suggest that low 25(OH)D levels are associated with glucose intolerance and insulin resistance[25, 26]. For a long time, 1,25(OH)D has been known to be a positive regulator of insulin secretion by pancreatic β cells [27].

Numerous studies have observed that obesity is a negative predictor of vitamin D status [11, 28]. Data from the sixth Tromso study, which was a longitudinal analysis, showed an inverse association between serum 25(OH)D concentration and BMI in over 10,000 adults[29]. Using data from the 1958 British birth cohort (n = 7,189), Hypponen and Power observed that 80 % of subjects (BMI > or = 30 kg/m2) had a 25(OH)D less than 75 nmol/L, compared with 68 % of the non-obese subjects[30].

To our knowledge, there is no report of an association between MetS and BMI with vitamin D concentrations in rheumatoid arthritis. The findings of our study are consistent with those of non-RA-affected individuals and suggest that; despite treatment with physiologic doses of Vit D, the inverse association between vitamin D and MetS is also persistent among RA patients. In our study, serum 25-hydroxyvitamin D levels were inversely correlated with BMI.

Inflammation has been long recognized as a hallmark of RA and plays a remarkable role in the development of type 2 diabetes mellitus and MetS. Several lines of evidence now suggest that atherosclerosis also has an important inflammatory component [31]. Many of the cells comprising the inflammatory infiltrate in the joint lining are likewise found in atherosclerotic plaques [32].

Vitamin D has anti-inflammatory effects on RA patients, which may explain its protective role in type 2 diabetes mellitus and cardiovascular diseases [33]. Vitamin D may lower the risk of metabolic syndrome in RA by reducing the heightened inflammation associated with the disease [34]. Actions including suppression of vascular calcification, inhibition of vascular smooth muscle proliferation, modulation of inflammatory cytokines, and regulation of the renin–angiotensin system have all been described [35]. In this study, we found a significant difference in hypertension and fasting blood sugar among patients with or without MetS, which is in agreement with previous findings in RA patients.

Strength and limitation

One of the criticisms of the epidemiological studies linking low Vit D levels with MetS is the fact that Vit D is fat soluble and these associations may be simply representative of the larger volume of distribution of this vitamin in overweight individuals who are also prone to diabetes and MetS by virtue of their adiposity[36]. Hence, low Vit D levels may simply be as a result of adiposity without necessarily having a significant relation with MetS [37]. In this study, MetS had higher prevalence in patients with higher BMI; howbeit, there was not a significant correlation between these two parameters. This may stem from the more important role of abdominal obesity, which is considered as waist circumference, in comparison to BMI in prediction of MetS. On the other hand, adiposity was not prevalent in our subjects (average BMI = 26.8 ± 4 kg/m2) that could partially eliminate this error. Besides, our patients were under treatment with hydroxychloroquine and supplementary physiologic doses of Vit D that are reported to increase Vit D serum levels. Thus, relative higher levels of vitamin D in our patients; as a consequence of these treatments, did not affect these correlations.

Our study had some limitations. Since we used a cross-sectional design, we could not establish whether the relationship between MetS and Vit D levels is causal. Besides, different unknown confounders may affect Vit D serum values in a point of time; therefore, in the next step a longitudinal study should be designed to establish the casualty of these findings. In addition, participants were from Mashhad, Iran, a homogeneous population, potentially limiting the generalizability of our results.

Conclusion

To summarize, we suggested that 25(OH)D plays a protective role against MetS in RA patients. We also found an inverse relationship between BMI and vitamin D concentration in these patients. However, this cross-sectional study did not permit a power calculation on the causal relationship between Vit D and metabolic syndrome. Future long-term clinical trials should examine whether vitamin D supplementation can reduce MetS burden in RA patients or not.

Notes

Acknowledgments

This article was extracted from the thesis prepared by Mrs. Ladan Ghoshayeshi to fulfill the requirements needed for earning the internal medicine specialty degree. The Research Council of the Mashhad University of Medical Sciences, Mashhad, Iran is appreciated for financially supporting this study, grant number [87835]. We are grateful to all patients for their kind participation.

Disclosures

None.

References

  1. 1.
    Gabriel SE (2001) The epidemiology of rheumatoid arthritis. Rheum Dis Clin N Am 27:269–281CrossRefGoogle Scholar
  2. 2.
    Pincus T, Callahan LF, Sale WG, Brooks AL, Payne LE, Vaughn WK (1984) Severe functional declines, work disability, and increased mortality in seventy-five rheumatoid arthritis patients studied over nine years. Arthritis Rheum 27:864–872PubMedCrossRefGoogle Scholar
  3. 3.
    Solomon DH, Karlson EW, Rimm EB et al (2003) Cardiovascular morbidity and mortality in women diagnosed with rheumatoid arthritis. Circulation 107:1303–1307PubMedCrossRefGoogle Scholar
  4. 4.
    Grundy SM, Cleeman JI, Daniels SR et al (2005) Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute scientific statement: executive summary. Crit Path Cardiol 4:198–203CrossRefGoogle Scholar
  5. 5.
    Alexander CM, Landsman PB, Teutsch SM, Haffner SM (2003) NCEP-defined metabolic syndrome, diabetes, and prevalence of coronary heart disease among NHANES III participants age 50 years and older. Diabetes 52:1210–1214PubMedCrossRefGoogle Scholar
  6. 6.
    Isomaa B, Almgren P, Tuomi T et al (2001) Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care 24:683–689PubMedCrossRefGoogle Scholar
  7. 7.
    Ford ES, Zhao G, Li C, Pearson WS (2009) Serum concentrations of vitamin D and parathyroid hormone and prevalent metabolic syndrome among adults in the United States. J Diabetes 1:296–303PubMedCrossRefGoogle Scholar
  8. 8.
    Lu L, Yu Z, Pan A et al (2009) Plasma 25-hydroxyvitamin D concentration and metabolic syndrome among middle-aged and elderly Chinese individuals. Diabetes Care 32:1278–1283PubMedCrossRefGoogle Scholar
  9. 9.
    Reis JP, von Mühlen MD, Kritz-Silverstein D, Wingard DL, Barrett-Connor E (2007) Vitamin D, parathyroid hormone levels, and the prevalence of metabolic syndrome in community-dwelling older adults. Diabetes Care 30:1549–1555PubMedCrossRefGoogle Scholar
  10. 10.
    Cosenso-Martin LN, Vilela-Martin JF (2011) Is there an association between vitamin D and hypertension? Recent Patents Cardiovasc Drug Discov 6:140–147CrossRefGoogle Scholar
  11. 11.
    Foss YJ (2009) Vitamin D deficiency is the cause of common obesity. Med Hypotheses 72:314–321PubMedCrossRefGoogle Scholar
  12. 12.
    Muldowney S, Lucey AJ, Paschos G et al (2011) Relationships between vitamin D status and cardio-metabolic risk factors in young European adults. Ann Nutr Metab 58:85–93PubMedCrossRefGoogle Scholar
  13. 13.
    Albert PJ, Proal AD, Marshall TG (2009) Vitamin D: the alternative hypothesis. Autoimmun Rev 8:639–644PubMedCrossRefGoogle Scholar
  14. 14.
    Braun-Moscovici Y, Toledano K, Markovits D, Rozin A, Nahir AM, Balbir-Gurman A (2011) Vitamin D level: is it related to disease activity in inflammatory joint disease? Rheumatol Int 31:493–499PubMedCrossRefGoogle Scholar
  15. 15.
    Hewison M (2010) Vitamin D and the immune system: new perspectives on an old theme. Endocrinol Metab Clin North Am 39:365–379PubMedCrossRefGoogle Scholar
  16. 16.
    Holick MF (2007) Vitamin D deficiency. N Engl J Med 357:266–281PubMedCrossRefGoogle Scholar
  17. 17.
    Heshmat R, Mohammad K, Majdzadeh SR, Forouzanfar MH, Bahrami A, Ranjbar Omrani GH et al (2008) Vitamin D deficiency in Iran: a multi-center study among different urban Areas. Iranian J Publ Health 1:72–78Google Scholar
  18. 18.
    Aguado P, del Campo MT, Garces MV et al (2000) Low vitamin D levels in outpatient postmenopausal women from a rheumatology clinic in Madrid, Spain: their relationship with bone mineral density. Osteoporos Int 11:739–744PubMedCrossRefGoogle Scholar
  19. 19.
    Cutolo M, Otsa K, Uprus M, Paolino S, Seriolo B (2007) Vitamin D in rheumatoid arthritis. Autoimmun Rev 7:59–64PubMedCrossRefGoogle Scholar
  20. 20.
    Craig SM, Yu F, Curtis JR, Alarcón GS, Conn DL, Jonas B et al (2010) Vitamin D status and its associations with disease activity and severity in African Americans with recent-onset rheumatoid arthritis. J Rheumatol 37:275–281PubMedCrossRefGoogle Scholar
  21. 21.
    Chung CP, Oeser A, Solus JF et al (2008) Prevalence of the metabolic syndrome is increased in rheumatoid arthritis and is associated with coronary atherosclerosis. Atherosclerosis 196:756–763PubMedCrossRefGoogle Scholar
  22. 22.
    Zonana-Nacach A, Santana-Sahagun E, Jimenez-Balderas FJ, Camargo-Coronel A (2008) Prevalence and factors associated with metabolic syndrome in patients with rheumatoid arthritis and systemic lupus erythematosus. J Clin Rheumatol 14:74–77PubMedCrossRefGoogle Scholar
  23. 23.
    Sahebari M, Goshayeshi L, Mirfeizi Z, Rezaieyazdi Z, Hatef MR, Ghayour-Mobarhan M, Akhlaghi S, Sahebkar A, Ferns GA (2011) Investigation of the association between metabolic syndrome and disease activity in rheumatoid arthritis. Sci World J 11:1195–1205CrossRefGoogle Scholar
  24. 24.
    Reis JP, von Mühlen MD, Miller ER (2008) Relation of 25-hydroxyvitamin D and parathyroid hormone levels with metabolic syndrome among US adults. Eur J Endocrinol 159:41–48PubMedCrossRefGoogle Scholar
  25. 25.
    Chiu KC, Chu A, Go VL, Saad MF (2004) Hypovitaminosis D is associated with insulin resistance and beta cell dysfunction. Am J Clin Nutr 79:820–825PubMedGoogle Scholar
  26. 26.
    Liu E, Meigs JB, Pittas AG et al (2009) Plasma 25-hydroxyvitamin d is associated with markers of the insulin resistant phenotype in nondiabetic adults. J Nutr 139:329–334PubMedGoogle Scholar
  27. 27.
    Takiishi T, Gysemans C, Bouillon R, Mathieu C (2010) Vitamin D and diabetes. Endocrinol Metab Clin North Am 39:419–446PubMedCrossRefGoogle Scholar
  28. 28.
    Perez-Lopez FR (2009) Vitamin D metabolism and cardiovascular risk factors in postmenopausal women. Maturitas 62:248–262PubMedCrossRefGoogle Scholar
  29. 29.
    Jorde R, Sneve M, Emaus N, Figenschau Y, Grimnes G (2010) Cross-sectional and longitudinal relation between serum 25-hydroxyvitamin D and body mass index: the Tromso study. Eur J Nutr 49:401–407PubMedCrossRefGoogle Scholar
  30. 30.
    Hypponen E, Power C (2006) Vitamin D status and glucose homeostasis in the 1958 British birth cohort: the role of obesity. Diabetes Care 29:2244–2246PubMedCrossRefGoogle Scholar
  31. 31.
    Libby P (2008) Role of inflammation in atherosclerosis associated with rheumatoid arthritis. Am J Med 121:S21–S31PubMedCrossRefGoogle Scholar
  32. 32.
    Hurlimann D, Enseleit F, Ruschitzka F (2004) Rheumatoid arthritis, inflammation, and atherosclerosis. Herz 29:760–768PubMedCrossRefGoogle Scholar
  33. 33.
    Michos ED, Melamed ML (2008) Vitamin D and cardiovascular disease risk. Curr Opin Clin Nutr Metab Care 11:7–12PubMedCrossRefGoogle Scholar
  34. 34.
    Zittermann A, Frisch S, Berthold HK et al (2009) Vitamin D supplementation enhances the beneficial effects of weight loss on cardiovascular disease risk markers. Am J Clin Nutr 89:1321–1327PubMedCrossRefGoogle Scholar
  35. 35.
    van Etten EE, Mathieu C (2005) Immunoregulation by 1,25-dihydroxyvitamin D3: basic concepts. J Steroid Biochem Mol Biol 97:93–101PubMedCrossRefGoogle Scholar
  36. 36.
    Wortsman J, Matsuoka LY, Chen TC, Lu Z, Holick MF (2000) Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr 72:690–693PubMedGoogle Scholar
  37. 37.
    Luo C, Wong J, Brown M, Hooper M, Molyneaux L, Yue DK (2009) Hypovitaminosis D in Chinese type 2 diabetes: lack of impact on clinical metabolic status and biomarkers of cellular inflammation. Diabet Vasc Dis Res 6:194–199CrossRefGoogle Scholar

Copyright information

© Clinical Rheumatology 2012

Authors and Affiliations

  • Ladan Goshayeshi
    • 1
  • HamidReza Saber
    • 2
  • Maryam Sahebari
    • 2
    • 5
  • Zahra Rezaieyazdi
    • 2
  • Houshang Rafatpanah
    • 3
  • Habibollah Esmaily
    • 2
  • Lena Goshayeshi
    • 4
  1. 1.School of MedicineMashhad University of Medical SciencesMashhadIran
  2. 2.Rheumatic Diseases Research Center (RDRC), School of MedicineMashhad University of Medical SciencesMashhadIran
  3. 3.Immunology Research Center, School of MedicineMashhad University of Medical SciencesMashhadIran
  4. 4.Microbiology and Virology Research Center, Avesina Research Institute, School of MedicineMashhad University of Medical SciencesMashhadIran
  5. 5.Rheumatic Diseases Research Center (RDRC), Ghaem hospital, Faculty of MedicineMashhad University of Medical SciencesMashhadIran

Personalised recommendations