ASSESSMENT OF VITAMIN D ON METABOLIC DISORDERS IN ARTHRITIC PREDIABETIC PATIENTS- A PHARMACOLOGICAL APPROACH

ASSESSMENT OF VITAMIN D ON METABOLIC DISORDERS IN ARTHRITIC PREDIABETIC PATIENTS- A PHARMACOLOGICAL APPROACH

Venkatesh Gunasekaran ^*1, Swathi K Srinivasan ² and Sankar Veintramuthu ³

Department of Pharmacology ¹, PSG College of Pharmacy, Tamil Nadu, India.

Department of Rheumatology ², PSG institute of Medical science & Research, Tamil Nadu, India.

Department of Pharmacy practice ³, PSG College of Pharmacy, Tamil Nadu, India

ABSTRACT: We planned to clarify the association between the Vitamin D supplementation and predisposition of metabolic syndrome including obesity, diabetes mellitus, hypertension and dyslipidemia in arthritic patient with pre diabetic condition and to assess prediabetes interfere in the disease progression. Retrospective observational study was conducted on 236 patients. Of these, Arthritis patients with no co-morbid condition and not supplemented with Vitamin D (47), Arthritis patients supplementing with Vitamin D (63), Arthritis patients with prediabetic condition (68), Arthritic prediabetic patients supplementing with Vitamin D (58) were recruited based on inclusion and exclusion criteria. All anthropometric parameters and clinical findings were recorded the predominance of women with RA was observed in this study and the body weight was increased substantially in entire study group irrespective of gender. A significant increase in metabolic parameters was observed in patients with arthritis who were off of Vitamin D supplementation (p<0.05). On the other hand no such significant increase was observed in vitamin D supplemented group (p>0.05. In the group of arthritic patients with prediabetes condition significant increase in metabolic parameters (p<0.01). There was no deterioration rather an improvement during the Vitamin D supplementation in prediabetic arthritic patients but lipid parameters were increased gradually in continuous visit. Predisposition of metabolic disorder was reduced with Vitamin D supplement. Prediabetes has shown positive correlation with the disease activity in RA patients. Moreover less association was observed between the lipid profile and Vitamin D status

Vitamin D,

Rheumatoid arthritis, Prediabetes, Hypertension, lipid Profile.

INTRODUCTION: Rheumatoid arthritis (RA) is an autoimmune disorder that causes chronic inflammation and pain in joints associated with increased disability, morbidity and mortality ¹. Etiology of the disease is attributable to genetic and non genetic factors as hormonal, environmental, and infectious factors ².

Vitamin D deficiency is most common health problem in more than 50% of the general population worldwide. Nearly 30% of the RA patients were strongly related to the vitamin D deficiency, at the same line RA has inverse correlation with the serum Vitamin D ^{3, 4}. Epidemiological studies suggest that vitamin D has a role in insulin resistance, type 2 diabetes, obesity, metabolic and cardiovascular syndrome, which is associated with systemic, chronic inflammation by reducing the circulating levels of proinflammatory cytokines and C-reactive protein ^{5, 6, 7}.

Definition of metabolic syndrome is not yet clear since it has been tailored based on the race, age, dietary habits and also by disease specific factors. The main components of Metabolic syndrome are elevation of mean arterial blood pressure (BP) dyslipidemia (elevated triglycerides, low density lipoproteins (LDL) and low high-density lipoproteins (HDL)), and glucose intolerance, while insulin resistance and obesity have gained increasing attention as the core manifestations of the syndrome ²⁹. In recent decades, other abnormalities were also included such as sleep apnea, nonalcoholic fatty liver disease and prothrombotic states ³⁰.

Obesity is the most common risk factor for the prediabetes which is associated with hypovitaminosis due to inefficiency of adipose tissue to store 25-hydroxyvitamin-D ⁸. Inadequate amount of serum 25 (OH) D can stimulate the lipogenesis, predisposing a patient to further weight gain and thus increasing the risk of diabetes ⁹. Administration of Vitamin-D has been shown to decrease insulin resistance and increase the insulin sensitivity in diabetic patients. Henceforth it activates the pancreatic β cell function through the activation of Vitamin D receptor and by regulating peroxisome proliferator activated receptor (PPAR). Vitamin D may also affect insulin secretion and sensitivity indirectly by regulating extracellular calcium concentration in the beta cells and peripheral insulin-target tissues ^{10, 11}

Though arthritis is a major risk factor for the development of glucose intolerance and diabetes, prevalence and clinical associations are not well documented yet. Hence in the present study we planned to assess the role of vitamin D in the progression of prediabetes and other metabolic disorders in rheumatoid arthritis patients with prediabetic condition

 MATERIALS AND METHODS:

Retrospective observational study was approved by Institutional Human ethical committee, PSGIMS&R (IHEC-13/381) and conducted on Rheumatoid Arthritis (RA) patients admitted in Rheumatology department at PSG Hospital. Data of the patients were collected from May 2011 to November 2013. In total, 236 subjects were identified as Rheumatoid Arthritis from the clinical reports and randomly recruited for the study based on inclusion and exclusion criteria. The subjects were included  between age group of 30 to 65 years and diagnosed as RA with or without prediabetes (> 5.6 mmol/L) and Serum 25(OH) D (<25 ng/ml). The Subjects were excluded if the patients were suffering from chronic alcoholism, hepatic failure, cardiovascular diseases, renal disorder and chronic infection. Rheumatoid Patients were classified based on pre diabetic condition and Vitamin D supplementation.

In Group 1: Arthritis patients with no comorbid condition and not supplemented with Vitamin D (47), Group 2: Arthritis patients supplementing with vitamin D (63), Group 3: Arthritis patients with prediabetic condition (68), Group 4: Arthritic prediabetic patients supplementing with vitamin D (58)   and all anthropometric parameters, physical examination findings, erythrocyte sedimentation rate (ESR) and hsCRP were observed. Medications used for RA, calcium and vitamin D supplements, anti-TNF agent and non steroidal anti-inflammatory drugs (NSAID), and disease-modifying anti Rheumatic drugs (DMARDs), including methotrexate, sulfasalazine, cyclosporine and prednisolone were documented. Patient data were collected in three continuous visits in the interval of three to four months.

Vitamin D deficiency was defined as a 25(OH) D serum level less than 15 ng/ml, vitamin D insufficiency as 25(OH)D levels of 15-20 ng/ ml, and severe vitamin D deficiency as 25(OH) D levels of less than 5 ng/ml. Vitamin D levels greater than 20 ng/ml were considered sufficient. HbA1c (<6%) as normal, HbA1c (6-6.4%) as prediabetes, HbA1c (>6.5%) as diabetes were Considered. Desired lipid profile TC<5.2 mmol/L, LDL < 2.6 mmol/L, HDL >1.3 mmol/L, and TG < 1.7 mmol/L. higher sensitive CRP<0.6mg/dl, Erythrocyte Sedimentation Rate (ESR) 0-22 mm/hr for men,  and 0-29 mm/hr  for women are obtained from respective associations.

Statistical analysis:

Documented data were analyzed by using Analysis of Variance (ANOVA) and Student‘t’ test by using prism software (user guide 6.1). Statistical significance was taken at the 95% level (P < 0.05). Results were expressed as Mean ± Standard Deviation.

 RESULTS:

Baseline Characteristics of the Study Population:

Demographic and clinical characteristics of patients included in this study are summarized in Table. There was a predominance of women in the entire group with RA, little varied in prediabetes group.  The mean ages in all the groups were almost 40 - 50 years. Body weight increased in all the groups. During the study period patient underwent  different treatment regimen such as NSAIDs  and calcium (6.8%), DMARDs , NSAIDs and calcium (13.9%), DMARDs, NSAIDs, calcium and Prednisolone (14.3%), DMARDs  and  NSAIDs (4.6%), DMARDs,  NSAIDs and Etanercept(2.5%), DMARDs, NSAIDs,  calcium and  Allopurinol (0.42%),  Vitamin D3 with other drugs ( 50.8%) as mentioned in different tables  based on the group.

 Changes of metabolic parameters in patient with Arthritic Condition:

At the time of recruitment the mean BMI of the RA group was 25- 30 (kg/m2) indicating an obese sample. BMI and fasting glucose were gradually increased between the visit and they were showed statistically significant (p<0.01). We observed that the subjects in this group had Vitamin D insufficiency and it was significantly increased even at the last visit (p<0.04). During the first and second visit HbA1c level was within the normal range, whereas at the end of the third visit increased to 6.1% (p<0.05) which indicates prediabetic condition. No significant differences were found between the visit in diastolic pressure, whereas differences in systolic pressure was significant (p<0.05).

The mean value of ESR showed to be normal at the initial visit which was significantly increased in later visits (p<0.05). At the beginning, all the lipid parameters were optimal or near normal range, on later stage it changed remarkably,  total CHO(p<0.05), LDL (p<0.05) and TGL (p<0.05) greatly increased and HDL (p<0.05) was significantly decreased in later visits. The mean value of CRP level was significantly increased between the visits (p<0.05) as disease progression increased (Table 1).

The changes in metabolic parameters of arthritic patient supplemented with vitamin D has not shown any significant increase in BMI (p>0.05) although body weight has increased gradually. On the other hand systolic (p=0.062) and diastolic (p=0.093) BP was not showing any significant increase in this group. There was a marked decrease in the average fasting glucose level from 5.8 to 5.5 mmol/L (p<0.05).

In lipid profile analysis, we found that the mean score was slightly increased in total CHO and TG level, but not statistically significant (p>0.05).whereas HDL and LDL level were significantly improved between the visits (p<0.05).The mean value of vitamin D has improved to near normal range (p=0.023) on vitamin D supplementation. In the same way decrement of hsCRP level was observed in these patients (p<0.05) (Table 2).

 Changes of metabolic parameters in Arthritic patient with prediabetes:

Table 3 demonstrates that condition worsened significantly among the visits in Arthritis patient with prediabetes with regard to weight, BMI (p=0.01), HbA1c (p = 0.05), fasting glucose (p = 0.02), ESR (p = 0.05), Blood pressure (p=0.01), lipid profile (p=0.01) and hsCRP (p=0.05).The mean value of Vitamin D decreased significantly (p = 0.05) as disease progression increased.

Arthritic prediabetic patient supplemented with vitamin D group failed to show any significant increase in weight, BMI (p=0.13),fasting glucose (p = 0.07), systolic BP (p=0.07), total CHO.(p=0.12), LDL (p=0.09),TG(p = 0.13), HDL(p = 0.09) and ESR(p = 0.09) at the same time steady state of  the mean values were maintained. In other hand HbA1c (p = 0.05), diastolic BP (p = 0.05), hsCRP (p = 0.04) and 25(OH) D (p = 0.05) were significantly improved in continuous visit that indicates disease activity is greatly improved (Table 4).

TABLE 1: CHANGES OF METABOLIC PARAMETERS IN ARTHRITIS PATIENTS

Data presented as mean ± standard error; NS – not significant; significance at p < 0.05. To convert the values for glucose to millimoles per liter, multiply by 0.05551. To convert the values for triglycerides to millimoles per liter, multiply by 0.01129. To convert the values for cholesterol to millimoles per liter, multiply by 0.02586.

TABLE 2: CHANGES OF METABOLIC PARAMETERS IN ARTHRITIS PATIENTS SUPPLEMENTED WITH VITAMIN D

Data presented as mean ± standard error; NS – not significant; significance at p < 0.05. To convert the values for glucose to millimoles per liter, multiply by 0.05551. To convert the values for triglycerides to millimoles per liter, multiply by 0.01129. To convert the values for cholesterol to millimoles per liter, multiply by 0.02586.

TABLE 3:  CHANGES OF METABOLIC PARAMETERS IN ARTHRITIS PATIENT WITH PREDIABETES

Data presented as mean ± standard error; NS – not significant; significance at p < 0.05. To convert the values for glucose to millimoles per liter, multiply by 0.05551. To convert the values for triglycerides to millimoles per liter, multiply by 0.01129. To convert the values for cholesterol to millimoles per liter, multiply by 0.02586.

TABLE 4: CHANGES OF METABOLIC PARAMETERS IN ARTHRITIC PREDIABETIC PATIENT SUPPLEMENTED WITH VITAMIN D

Data presented as mean ± standard error; NS – not significant; significance at p < 0.05. To convert the values for glucose to millimoles per liter, multiply by 0.05551. To convert the values for triglycerides to millimoles per liter, multiply by 0.01129. To convert the values for cholesterol to millimoles per liter, multiply by 0.02586.

TABLE 5: PATIENTS PREDISPOSED TO DIFFERENT METABOLIC DISORDER AT THE END OF THE STUDY

Data presented as percentages (%).Conditions are obtained based on the diabetes, hypertension and dyslipidemia guidelines.

DISCUSSION: The study was designed to assess the association between vitamin D supplementation and predisposition of prediabetes in arthritic patients, Another objective of this study is to evaluate the relationship between vitamin D3 use, the rate of onset and prevalence of metabolic syndrome such as hypertension, diabetes and dyslipidemia condition. Vitamin D deficiency and lack of vitamin D supplementation is the major hallmark for the most of the metabolic disorders ¹². Awareness and importance about the vitamin D sufficiency has increased in recent decades even in optimal healthy volunteers. Surprisingly urban subjects with age >50 are well affected by vitamin D deficiency than rural subjects, which might be due to less exposure to sunlight  and less physical activity relating to calcium dysregulation ¹³.

In this study, fairly female subjects were enrolled more than the male subjects, indicating that females are more prone to RA. Also they have early onset of RA and high prevalence rate. This might be due to unusual sex hormone shifting since estrogen is a good predictor for the up regulating immunoglobulin production ¹⁴. Virtually 12-20% of the subjects in non vitamin D group are higher predisposition rate to obese condition than vitamin D supplemented group. Irrespectively mean value of body mass index ratio was increased in all the groups these results in consistent with our previous reports which indicates that BMI was reduced in patients supplemented with vitamin D or sunlight exposure ³¹ these changes probably is due to synergistic role of RA with prediabetes might dominate the therapeutic effect of vitamin D or by increasing the lipogenesis.

Gradual raise of mean fasting glucose level was observed in non vitamin D groups this might be due to glucose intolerance or inability  to secrete insulin from pancreatic β cells due to  lack of vitamin D since all the subjects in this group are state of vitamin D deficiency which is similar to our previous report ¹⁵. On the contrary, subjects supplemented with vitamin D have not shown any improvement in the blood glucose reduction but the values are remained unvaried. Hence, the study clearly indicates that RA patient supplemented with vitamin D has less risk of prediabetes compared to non vitamin D patients and it seems that vitamin D might maintain or improve the insulin resistance and insulin sensitivity ¹⁰. At the same time rate of predisposition of prediabetes has reduced nearly 20% in vitamin D supplemented group as compared to non vitamin D group. Notable increase of patients shifting from the prediabetic to the Type 2 DM condition(12% to 17%) in not vitamin D group was observed which is consistent with Wasko MC et al study this is probably due to inflammation induced insulin resistance activity since vitamin D has been predicted as a good anti inflammatory agent ^{16, 17}.

The prevalence of hypertension is considerably higher about 42% in RA than in the average population due to systemic, low-grade inflammation and physical inactivity ¹⁸. Study point out that remarkable increase of BP in non vitamin D subjects might be due to low grade systemic inflammation. This can lead to hypertension by reducing nitric oxide production in endothelial cells, leading to vasoconstriction, increased production of endothelin-1 ¹⁹. However  vitamin D play a major role in the subsiding systemic and low grade inflammation by reducing hsCRP which is the primary marker for the inflammation ¹⁸. In our study approximately 5-10% of the non vitamin D groups are more susceptible to the cardiovascular risk than the vitamin D supplemented groups. In addition to that we observed 2-3% of the non vitamin D groups were entered into the secondary hypertensive condition in short period.

It was also observed that, ESR was greatly reduced in vitamin D supplemented group which indicates that immunomodulatory effect of vitamin D could also produce anti inflammatory, anti diabetic, anti obesity and anti arthritic effect via endocrine and paracrine manner ²⁰ by decreasing antigen presentation and inhibiting the proinflammatory helper T cells.  In view of the fact that ESR is a good predictor for the inflammatory response ^{21, 22} moreover hsCRP is also significantly increased in  non vitamin D group which can up regulate the expression of AT1 receptors and activate rennin angiotensin system (RAS) that could  increase the arterial blood pressure  this is probably due to vitamin D deficiency or inadequate sunlight exposure and  utilization of vitamin D by the body cells because serum vitamin D is an important biological marker for regulating the hsCRP level in blood ¹⁷ and significant decrease of blood hsCRP  was found in vitamin D supplemented group  these changes  might be due to anti obesity and anti inflammatory activity of vitamin D since obesity has a role in increase the CRP level in blood ¹⁵ these factors could also be a reason for the reduction of BMI in vitamin D group. At the same time disease activity is greatly reduced in this groups which might be due to anti inflammatory activity of vitamin D by controlling cytokines release and immune tolerance ^{23, 24}.

Tendency towards the changes in TC, LDL, HDL and TG were not showing significant improvement in any group with the supplementation of vitamin D these results matches with the report of Kane et al ²⁵. In fact some studies reported positive correlation with vitamin D ²⁸. In respect to this concept few studies reported that source of vitamin D is important in regulating lipid profile. Saedisomeolia et al reported that sunlight exposure is very effective than the vitamin D supplementation ^{10, 32}.

In our previous report vitamin D has not shown positive correlation with the LDL, TG and TC but not in HDL level ³¹. Even in the present study we found subjects are predisposed to dyslipidemia condition is invariably. Such controversial report between the studies might be due to duration of study period or co-morbidity of the disease condition or mode of vitamin D exposure ^{26, 27}

In conclusion, study reveals that RA has a link with increased prevalence and predisposition of metabolic syndrome. Our study also revealed, among the parameters lipid profile have shown less association with the vitamin D supplementation possibly due to less exposure of sunlight or inadequate intake of vitamin D. While in vitamin D supplementation, disease activity is comparatively less in arthritis patient than in arthritic prediabetic patients. Moreover, study also reveals that pre diabetes might have positive correlation with the disease activity in RA patients. However, prospective comprehensive studies are needed to further investigate the relationship between RA, vitamin D and prediabetes.

 ACKNOWLEDGMENTS: We acknowledge Dr. M. Ramanathan, Head of the institution, PSG College of Pharmacy and PSG Hospitals for granting permission and providing valuable support.

 CONFLICTS OF INTEREST STATEMENT: The authors declare that there are no conflicts of interest.

 REFERENCES:

1. Pieringer H, Pichler M: Cardiovascular morbidity and mortality in patients with rheumatoid arthritis: vascular alterations and possible clinical implications. QJM 2011;104(1):13-26.
2. Manole Cojocaru, Inimioara Mihaela Cojocaru, Isabela Silosi, Camelia Doina Vrabie and R Tanasescu^: Extra-articular Manifestations in Rheumatoid Arthritis. Maedica (Buchar) 2010; 5(4): 286–291.
3. Ranganathan P, Khalatbari S, Yalavarthi S, Marder W, Brook R and Kaplan MJ: Vitamin D deficiency, interleukin 17, and vascular function in rheumatoid arthritis. J Rheumatol 2013; 40:1529–34.
4. Moghimi J, Sadeghi A, Malek M, Ghorbani R: Relationship between disease activity and serum levels of vitamin D and parathyroid hormone in rheumatoid arthritis. Endocr Regul 2012 Apr;46(2):61-6.
5. Zold E, Barta Z and Bodolay E: Vitamin D deficiency and connective tissue disease. Vitam Horm 2011;86:261-86.
6. Kai Yin: Vitamin D and inflammatory diseases. J Inflamm Res 2014; 7: 69–87.
7. Grudet C, Malm J, Westrin A and Brundin L: Suicidal patients are deficient in vitamin D, associated with a pro-inflammatory status in the blood. Psychoneuroendocrinology 2014; 50:210-9.
8. Leung PS: The Potential Protective Action of Vitamin D in Hepatic Insulin Resistance and Pancreatic Islet Dysfunction in Type 2 Diabetes Mellitus. Nutrients 2016; 5;8(3).

9. Ganie MA, Marwaha RK, Nisar S, Farooqi KJ, Jan RA, Wani SA, Gojwari T and Shah ZA: Impact of hypovitaminosis D on clinical, hormonal and insulin sensitivity parameters in normal body mass index polycystic ovary syndrome women. J Obstet Gynaecol 2016;15:1-5
10. Carter LG, Ngo Tenlep SY, Woollett LA and Pearson KJ: Exercise Improves Glucose Disposal and Insulin Signaling in Pregnant Mice Fed a High Fat Diet. J Diabetes Metab 2015;6(12
11. Gagnon C, Daly RM, Carpentier A, Lu ZX, Shore-Lorenti C, Sikaris K, Jean S and Ebeling PR: Effects of combined calcium and vitamin D supplementation on insulin  secretion, insulin sensitivity and β-cell function in multi-ethnic vitamin D-deficient adults at risk for type 2 diabetes: a pilot randomized, placebo-controlled trial. PLoS One 2014; 9; 9(10).
12. Awad AB, Alappat L and Valerio M: Vitamin d and metabolic syndrome risk factors: evidence and mechanisms. Crit Rev Food Sci Nutr 2012; 52(2):103-12.
13. Marwaha RK, Tandon N, Garg MK, Kanwar R, Narang A, Sastry A, Saberwal A and Bandra K: Vitamin D status in healthy Indians aged 50 years and above. J Assoc Physicians India 2011;59: 706-9.
14. Khan D, Ansar Ahmed S: The Immune System Is a Natural Target for Estrogen Action: Opposing Effects of Estrogen in Two Prototypical Autoimmune Diseases. Front Immunol 2016 ;6;6:635.
15. Liang G, Song X, Xu H, Wang F, Zhang L, Zhou L and Jiang G: 3-Deoxyglucosone Induced Acute Glucose Intolerance in Sprague-Dawley Rats: Involvement of Insulin Resistance and Impaired β-cell Function. Exp Clin Endocrinol Diabetes 2016; 29(2)13-6.
16. Wasko MC, Kay J, Hsia EC and Rahman MU: Diabetes mellitus and insulin resistance in patients with rheumatoid arthritis: risk reduction in a chronic inflammatory disease. Arthritis Care Res (Hoboken) 2011; 63(4):512-21.
17. Hiremath VP, Rao CB, Naik V and Prasad KV: Anti-inflammatory effect of vitamin D on gingivitis: a dose-response randomised control trial. Oral Health Prev Dent 2013;11(1):61-9.
18. Nadkarni A, You M, Resuehr H, Curtis JR. The Risk for Cardiovascular Events Associated with Hyperlipdemia among Patients with and Without Rheumatoid Arthritis. J Arthritis 2015;4(4).
19. Desai RJ, Solomon DH, Schneeweiss S, Danaei G, Liao KP and Kim SC: Tumor necrosis factor-α inhibitor use and the risk of incident hypertension in patients with rheumatoid arthritis. Epidemiology 2016; 20.
20. Hewison M: Vitamin D and immune function: autocrine, paracrine or endocrine? Scand J Clin Lab Invest Suppl 2012; 243:92-102.
21. Wen H, Luo J, Zhang X, Zhang C, Zhao X, Wang X and Li X: [1,25(OH)2-Vitamin-D3 attenuates Th17-related cytokines expression in peripheral blood mononuclear cells in patients with early-diagnosed rheumatoid arthritis. Diabetol Metab Syndr 2015;54(4):317-21.
22. Bartels LE, Hvas CL, Agnholt J, Dahlerup JF and Agger R: Human dendritic cell antigen presentation and chemotaxis are inhibited by intrinsic 25-hydroxy vitamin D activation. Int Immunopharmacol 2010; 10(8):922-8.
23. Kim NH, Kim HY, An H, Seo JA, Kim NH, Choi KM, Baik SH, Choi DS, Kim SG. Effect of cilostazol on arterial stiffness and vascular adhesion molecules in type 2 diabetic patients with metabolic syndrome: a randomised, double-blind, placebo-controlled, crossover trial. Diabetol Metab Syndr. 2013 Jul 26;5(1):41.
24. Morettini M, Storm F, Sacchetti M, Cappozzo A, Mazzà C: Effects of walking on low-grade inflammation and their implications for Type 2 Diabetes. Prev Med Rep 2015; 16; 2:538-47.
25. Kane L, Moore K, Lütjohann D, Bikle D and Schwartz JB: Vitamin D3 Effects on Lipids Differ in Statin and Non-Statin-Treated Humans: Superiority              of Free 25- OH D Levels in Detecting Relationships.             J Clin Endocrinol Metab 2013; 98:440.
26. Ramankutty P, de Klerk NH, Miller M, Fenech M, O' Callaghan N, Armstrong BK: Ultraviolet radiation exposure and serum vitamin D levels in young children. J Paediatr Child Health 2014; 50(9):713-20.
27. Helli B, Mowla K, Mohammadshahi M and Jalali MT: Effect of Sesamin Supplementation on Cardiovascular Risk Factors in Women with Rheumatoid Arthritis. J Am Coll Nutr. 2015 Jul 7:1-8.
28. Wang, H, Xia, N, Yang, Y, Peng DQ: Influence of vitamin D supplementation on plasma lipid profiles: A meta-analysis of randomized controlled trials. Lipids in Health and Disease 2012; 11: 42.
29. Eva K, Panagiota Pervanidou, Gregory Kaltsas, George Chrousos: Metabolic syndrome: definitions and controversies. BMC Med 2011; 9:48.
30. Dimitroulas T, Hodson J, Sandoo A, Smith JP, Douglas KM, Kitas GD: Symmetric Dimethylarginine Is Not Associated with Cumulative Inflammatory Load or Classical Cardiovascular Risk Factors in Rheumatoid Arthritis: A 6-Year Follow-Up Study. Mediators Inflamm. 2015; 2015:796562.
31. Venkatesh G, Arsha jayprakash and swathi KS: The effect of sunlight exposure on prediabetic patients in south Indian population. Int j pharm pharm sci 2014; 6(11): 107-110.
32. Laragione T, Shah A and Gulko PS: The vitamin D receptor regulates rheumatoid arthritis synovial fibroblast invasion and morphology. Mol Med 2012; 18:194-200
    

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How to cite this article:

Gunasekaran V, Srinivasan SK and Veintramuthu S: Assessment of Vitamin D on Metabolic disorders in Arthritic prediabetic patients- a pharmacological approach. Int J Pharm Sci Res 2016; 7(6): 2648-55.doi: 10.13040/IJPSR.0975-8232.7(6).2648-55.

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