Angiology
http://ang.sagepub.com/
Vitamin D and Dysfunctional Adipose Tissue in Obesity Stokic Edita, Kupusinac Aleksandar, Tomic-Naglic Dragana, Smiljenic Dragana, Kovacev-Zavisic Branka, Srdic-Galic Biljana, Soskic Sanja and Isenovic R. Esma ANGIOLOGY published online 22 July 2014 DOI: 10.1177/0003319714543512 The online version of this article can be found at: http://ang.sagepub.com/content/early/2014/07/21/0003319714543512
Published by: http://www.sagepublications.com
Additional services and information for Angiology can be found at: Email Alerts: http://ang.sagepub.com/cgi/alerts Subscriptions: http://ang.sagepub.com/subscriptions Reprints: http://www.sagepub.com/journalsReprints.nav Permissions: http://www.sagepub.com/journalsPermissions.nav
>> OnlineFirst Version of Record - Jul 22, 2014 What is This?
Downloaded from ang.sagepub.com at COLUMBIA UNIV on August 18, 2014
Original Manuscript Angiology 1-6 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0003319714543512 ang.sagepub.com
Vitamin D and Dysfunctional Adipose Tissue in Obesity Stokic´ Edita, MD, PhD1, Kupusinac Aleksandar, PhD2, Tomic-Naglic Dragana, PhD1, Smiljenic Dragana, MD3, Kovacev-Zavisic Branka, MD, PhD1, Srdic-Galic Biljana, PhD3, Soskic Sanja, MSc4, and Isenovic R. Esma, PhD4
Abstract Vitamin D deficiency and dysfunctional adipose tissue are involved in the development of cardiometabolic disturbances (eg, hypertension, insulin resistance, type 2 diabetes mellitus, obesity, and dyslipidemia). We evaluated the relation between vitamin D and adipocytokines derived from adipose tissue. We studied 50 obese individuals who were classified into different subgroups according to medians of observed anthropometric parameters (body mass index, body fat percentage, waist circumference, and trunk fat mass). There was a negative correlation between vitamin D level and leptin and resistin (r ¼ -.61, P < .01), while a positive association with adiponectin concentrations was found (r ¼ .7, P < .001). Trend estimation showed that increase in vitamin D level is accompanied by intensive increase in adiponectin concentrations (growth coefficient: 12.13). In conclusion, a positive trend was established between vitamin D and the protective adipocytokine adiponectin. The clinical relevance of this relationship needs to be investigated in larger studies. Keywords vitamin D, dysfunctional adipose tissue, obesity, adipocytokine
Introduction The prevalence of obesity is increasing worldwide. The increase in fat mass results in metabolic disturbances, such as insulin resistance, atherogenic dyslipidemia, and hypertension.1,2 Also, obesity is a well-established risk factor for the development of cardiovascular (CV) disorders (coronary artery disease, stroke, and myocardial infarction), which are leading causes of death.3 Adipose tissue stores energy, but the secretory products of adipocytes have been implicated in the pathogenesis of obesity-related metabolic disturbances. Namely, adipose tissue produces several bioactive peptides, known as adipocytokines, including leptin, tumor necrosis factor a, interleukin 6, adiponectin, and resistin.4 Proinflammatory and proatherogenic adipocytokines are involved in the development of insulin resistance, type 2 diabetes mellitus, and atherosclerosis.5 It has been shown that in obese patients with dysfunctional adipose tissue, leptin levels are elevated, while a reduction in caloric intake is accompanied by reduced leptin concentration.6 Additionally, it has been reported that resistin influences the occurrence of metabolic syndrome, a state characterized by metabolic, proinflammatory, and prothrombotic abnormalities.7-9 In contrast, adiponectin exerts protective actions against the metabolic and CV complications of obesity. Individuals with increased fat mass have low adiponectin levels, and it seems that adiponectin prevents further progression of insulin resistance and reduces the
progression of atherosclerosis.10 Subcutaneous and visceral adipose tissues manifest different morphological and functional characteristics. In this regard, dysfunctional changes in adipose tissue are particularly expressed in visceral fat depots.11,12 In recent years, there has been an increased interest in the other roles of vitamin D, in addition to those on the skeletal system. Serum concentrations of 25-hydroxyvitamin D, 25(OH)D, 38.4 kg/m2, our results demonstrated significant negative correlation between 25(OH)D and leptin serum levels (r ¼ -.61, P < .01). Leptin has been proposed to be involved in the energy homeostasis and insulin sensitivity modulation,30 also being positively associated with visceral adipose mass.31,32 Recent studies have revealed that serum levels of leptin are inversely associated with serum 25(OH)D,33 which is in agreement with our results. As a proinflammatory cytokine, resistin affects lipid metabolism, glucose tolerance, and may play a role in the pathogenesis of metabolic syndrome.34 The available data are dual with respect to its relation to vitamin D deficiency—our study noted a negative correlation of 25(OH)D with resistin serum levels (r ¼ -.6, P < .05), while in other investigations this relationship was not found.21,35 Negative correlation of leptin and resistin with 25(OH)D was statistically significant only in subgroup of patients with greater BMI. After considering the linear dependence and trend between 25(OH)D level and leptin and resistin, we found that they are at inverse dependence: with higher vitamin D levels, leptin and resistin have a downward trend. This is the case in all obese subgroups, whether they are above or below the anthropometric medians. In contrast to leptin and resistin, adiponectin exerts antiatherogenic, anti-inflammatory, and antiplatelet features.36 As such, its concentration is reduced in the presence of obesity, type 2 diabetes mellitus, and metabolic syndrome.37 Additionally, adiponectin serum levels have been positively associated with plasma 25(OH)D38,39; our results are in agreement with these findings. Namely, in the subgroup of patients with a higher degree of obesity, a significant positive correlation was noted between 25(OH)D and adiponectin levels (r ¼ .7, P < .001). The connection became clearer after the trend estimation, which has shown that vitamin D level increase is followed by ascending tendency of adiponectin levels. The intensive increase in adiponectin was established in the subgroup of BMI >38.4 kg/m2 with GC of 12.13. This finding may be of importance in the context of therapeutic options for vitamin D, since both the factors are implicated in the development of several cardiometabolic disturbances.17,40 Also, numerous previous studies proved that intra-abdominal obesity has a direct impact on increased CV risk due to the increased action of proinflammatory and proatherogenic cytokines.41,42 In our study, increase in adiponectin was also detected within the subgroups of patients who have larger WC and FAT trunk, with GCs of 4.3 and 4. This implies that
changes in abdominal fat mass have an impact on the 25(OH)D–adiponectin relation. In the view of present findings, we suggest that vitamin D supplementation may have a beneficial effect on obesity via modulation of adipocytokine secretions. Since the dysfunctional adipose tissue is a trigger for cardiometabolic disturbances in obese patients, interventional trials are required to establish whether vitamin D supplementation could be a therapeutic option for improving adipose tissue function and thus prevent obesity-related diseases.
Limitations We did not have specific information about sunlight exposure and vitamin D obtained from food. Additionally, the number of patients in our study was small. Finally, since our study is cross-sectional, causality cannot be determined. Authors’ Note This manuscript has not been published and is not being considered for publishing elsewhere, and it is not presented or submitted for international conferences, in any language. Edita Stokic´, Branka Kovacˇev-Zavisˇic´, and Esma Isenovic´ substantially contributed to concept and design. Aleksandar Kupusinac, Dragana Tomic´-Naglic´, and Dragana Smiljenic´ contributed to acquisition of data, analysis, and interpretation. Edita Stokic´, Biljana Srdic´-Galic´, and Dragana Smijenic´ contributed to drafting the article. Edita Stokic´, Sanja Soskic´, Esma Isenovic´, and Dragana Tomic´-Naglic´ contributed to final approval of the version to be published.
Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was partially supported by (grant numbers 174026, III044006, and 173033) the Ministry of Education, Science and Technological Development of the Republic of Serbia.
References 1. Must A, Strauss RS. Risks and consequences of childhood and adolescent obesity. Int J Obes Relat Metab Disord. 1999; 23(suppl 2):S2-S11. 2. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults—the evidence report. National institutes of health. Obes Res. 1998;6(suppl 2): 51S-209S. 3. WHO. Global health risk: mortality and burden of diseases attributable to selected major risks 2009. http://www.who.int/ healthinfo/global_burden_disease/GlobalHealthRisk_report_full. pdf. (Accessed on October 28, 2009) 4. Tomic´-Naglic´ D SE, Srdic´ B, Radovanov T. Masno tkivo kao endokrina zˇlezda. Medicina Danas. 2008;7(4-6):142-147. 5. Murdolo G, Smith U. The dysregulated adipose tissue: a connecting link between insulin resistance, type 2 diabetes mellitus and
Downloaded from ang.sagepub.com at COLUMBIA UNIV on August 18, 2014
Edita et al
6. 7.
8.
9.
10.
11.
12.
13.
14. 15.
16.
17.
18.
19.
20.
21.
5
atherosclerosis. Nutr Metab Cardiovasc Dis. 2006;16(suppl 1): S35-S38. Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab. 2004;89(6):2548-2556. Aquilante CL, Kosmiski LA, Knutsen SD, Zineh I. Relationship between plasma resistin concentrations, inflammatory chemokines, and components of the metabolic syndrome in adults. Metabolism. 2008;57(4):494-501. Ohmori R, Momiyama Y, Kato R, et al. Associations between serum resistin levels and insulin resistance, inflammation, and coronary artery disease. J Am Coll Cardiol. 2005;46(2): 379-380. Katsiki N, Athyros VG, Karagiannis A, Mikhailidis DP. Characteristics other than the diagnostic criteria associated with metabolic syndrome: an overview [published online April 25, 2013]. Curr Vasc Pharmacol. 2013. Koerner A, Kratzsch J, Kiess W. Adipocytokines: leptin—the classical, resistin—the controversial, adiponectin—the promising, and more to come. Best Pract Res Clin Endocrinol Metab. 2005;19(4):525-546. Misra A, Vikram NK. Clinical and pathophysiological consequences of abdominal adiposity and abdominal adipose tissue depots. Nutrition. 2003;19(5):457-466. Stokic´ E, Srdic´ Galic´ B, Tomic´-Naglic´ D, Isenovic´ E. Sagittal abdominal diameter (SAD) in identification obese patients of higher cardiovascular risk. Cardiology. 2013;126:169. Bischoff-Ferrari HA, Giovannucci E, Willett WC, Dietrich T, Dawson-Hughes B. Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr. 2006;84(1):18-28. Vanlint S. Vitamin D and obesity. Nutrients. 2013;5(3):949-956. 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):820-825. Scragg R, Sowers M, Bell C. Third National H, nutrition examination S. Serum 25-hydroxyvitamin D, diabetes, and ethnicity in the third national health and nutrition examination survey. Diabetes Care. 2004;27(12):2813-2818. Anderson JL, May HT, Horne BD, et al. Relation of vitamin D deficiency to cardiovascular risk factors, disease status, and incident events in a general healthcare population. Am J Cardiol. 2010;106(7):963-968. Earthman CP, Beckman LM, Masodkar K, Sibley SD. The link between obesity and low circulating 25-hydroxyvitamin D concentrations: considerations and implications. Int J Obes (Lond). 2012;36(3):387-396. Stokic E, Kupusinac A, Tomic-Naglic D, et al. Obesity and vitamin D deficiency: trends to promote a more proatherogenic cardiometabolic risk profile [published online March 21, 2014]. Angiology. 2014. Need AG, O’Loughlin PD, Horowitz M, Nordin BE. Relationship between fasting serum glucose, age, body mass index and serum 25 hydroxyvitamin D in postmenopausal women. Clin Endocrinol (Oxf). 2005;62(6):738-741. Vilarrasa N, Vendrell J, Maravall J, et al. Is plasma 25(OH)D related to adipokines, inflammatory cytokines and insulin
22.
23.
24.
25.
26. 27. 28.
29.
30.
31.
32.
33.
34.
35.
36.
37. 38.
resistance in both a healthy and morbidly obese population? Endocrine. 2010;38(2):235-242. Kempt Am SM, Li C, Kaur H, Huang Tt. Leptin is a maker of body fat and hyperinsulinemia in college students. J Am Coll Nutr. 2006;55(3):175-180. Kim M, Na W, Sohn C. Correlation between vitamin D and cardiovascular disease predictors in overweight and obese Koreans. J Clin Biochem Nutr. 2013;52(2):167-171. Liu E, Meigs JB, Pittas AG, et al. Plasma 25-hydroxyvitamin D is associated with markers of the insulin resistant phenotype in nondiabetic adults. J Nutr. 2009;139(2):329-334. Al-Daghri NM, Al-Attas OS, Alokail MS, et al. Hypovitaminosis D associations with adverse metabolic parameters are accentuated in patients with type 2 diabetes mellitus: a body mass indexindependent role of adiponectin? J Endocrinol Invest. 2013; 36(1):1-6. Lips P. Worldwide status of vitamin D nutrition. J Steroid Biochem Mol Biol. 2010;121(1-2):297-300. Liel Y, Ulmer E, Shary J, Hollis BW, Bell NH. Low circulating vitamin D in obesity. Calcif Tissue Int. 1988;43(4):199-201. Hyldstrup L, Andersen T, Mcnair P, Breum L, Transbol I. Bone metabolism in obesity: changes related to severe overweight and dietary weight reduction. Acta Endocrinol (Copenh). 1993; 129(5):393-398. Wortsman J, Matsuoka LY, Chen TC, Lu Z, Holick MF. Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr. 2000;72(3):690-693. Kong J, Chen Y, Zhu G, Zhao Q, Li YC. 1,25-Dihydroxyvitamin D3 upregulates leptin expression in mouse adipose tissue. J Endocrinol. 2013;216(2):265-271. Indulekha K, Anjana RM, Surendar J, Mohan V. Association of visceral and subcutaneous fat with glucose intolerance, insulin resistance, adipocytokines and inflammatory markers in Asian Indians (CURES-113). Clin Biochem. 2011;44(4):281-287. Ding C, Parameswaran V, Cicuttini F, et al. Association between leptin, body composition, sex and knee cartilage morphology in older adults: the Tasmanian older adult cohort (TASOAC) study. Ann Rheum Dis. 2008;67(9):1254-1256. Maetani M, Maskarinec G, Franke AA, Cooney RV. Association of leptin, 25-hydroxyvitamin D, and parathyroid hormone in women. Nutr Cancer. 2009;61(2):225-231. Abate N, Sallam HS, Rizzo M, et al. Resistin: an inflammatory cytokine. Role in cardiovascular diseases, diabetes and the metabolic syndrome [published online December 5, 2013]. Curr Pharm Des. 2013. Roth CL, Elfers C, Kratz M, Hoofnagle AN. Vitamin D deficiency in obese children and its relationship to insulin resistance and adipokines. J Obes. 2011;2011:495101. Ohashi K, Ouchi N, Matsuzawa Y. Anti-inflammatory and antiatherogenic properties of adiponectin. Biochimie. 2012;94(10): 2137-2142. Scherer PE. Adipose tissue: from lipid storage compartment to endocrine organ. Diabetes. 2006;55(6):1537-1545. Nimitphong H, Chanprasertyothin S, Jongjaroenprasert W, Ongphiphadhanakul B. The association between vitamin D status and circulating adiponectin independent of adiposity in subjects
Downloaded from ang.sagepub.com at COLUMBIA UNIV on August 18, 2014
6
Angiology
with abnormal glucose tolerance. Endocrine. 2009;36(2): 205-210. 39. Roth CL, Kratz M, Ralston MM, Reinehr T. Changes in adiposederived inflammatory cytokines and chemokines after successful lifestyle intervention in obese children. Metabolism. 2011;60(4): 445-452. 40. Vaidya A, Williams JS, Forman JP. The independent association between 25-hydroxyvitamin D and adiponectin and its relation
with BMI in two large cohorts: the NHS and the HPFS. Obesity (Silver Spring). 2012;20(1):186-191. 41. Kupusinac A SE, Srdic´ Galic´ B. Determination of WHtR limit for predicting hyperglycemia in obese persons by using artificial neural networks. TEM J. 2012;1(4):270-272. 42. Stokic´ E, Kupusinac A, Doroslovacˇki R. Estimating SAD lowlimits for the adverse metabolic profile by using artificial neural networks. TEM J. 2013(2):115-119.
Downloaded from ang.sagepub.com at COLUMBIA UNIV on August 18, 2014
http://ang.sagepub.com/
Vitamin D and Dysfunctional Adipose Tissue in Obesity Stokic Edita, Kupusinac Aleksandar, Tomic-Naglic Dragana, Smiljenic Dragana, Kovacev-Zavisic Branka, Srdic-Galic Biljana, Soskic Sanja and Isenovic R. Esma ANGIOLOGY published online 22 July 2014 DOI: 10.1177/0003319714543512 The online version of this article can be found at: http://ang.sagepub.com/content/early/2014/07/21/0003319714543512
Published by: http://www.sagepublications.com
Additional services and information for Angiology can be found at: Email Alerts: http://ang.sagepub.com/cgi/alerts Subscriptions: http://ang.sagepub.com/subscriptions Reprints: http://www.sagepub.com/journalsReprints.nav Permissions: http://www.sagepub.com/journalsPermissions.nav
>> OnlineFirst Version of Record - Jul 22, 2014 What is This?
Downloaded from ang.sagepub.com at COLUMBIA UNIV on August 18, 2014
Original Manuscript Angiology 1-6 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0003319714543512 ang.sagepub.com
Vitamin D and Dysfunctional Adipose Tissue in Obesity Stokic´ Edita, MD, PhD1, Kupusinac Aleksandar, PhD2, Tomic-Naglic Dragana, PhD1, Smiljenic Dragana, MD3, Kovacev-Zavisic Branka, MD, PhD1, Srdic-Galic Biljana, PhD3, Soskic Sanja, MSc4, and Isenovic R. Esma, PhD4
Abstract Vitamin D deficiency and dysfunctional adipose tissue are involved in the development of cardiometabolic disturbances (eg, hypertension, insulin resistance, type 2 diabetes mellitus, obesity, and dyslipidemia). We evaluated the relation between vitamin D and adipocytokines derived from adipose tissue. We studied 50 obese individuals who were classified into different subgroups according to medians of observed anthropometric parameters (body mass index, body fat percentage, waist circumference, and trunk fat mass). There was a negative correlation between vitamin D level and leptin and resistin (r ¼ -.61, P < .01), while a positive association with adiponectin concentrations was found (r ¼ .7, P < .001). Trend estimation showed that increase in vitamin D level is accompanied by intensive increase in adiponectin concentrations (growth coefficient: 12.13). In conclusion, a positive trend was established between vitamin D and the protective adipocytokine adiponectin. The clinical relevance of this relationship needs to be investigated in larger studies. Keywords vitamin D, dysfunctional adipose tissue, obesity, adipocytokine
Introduction The prevalence of obesity is increasing worldwide. The increase in fat mass results in metabolic disturbances, such as insulin resistance, atherogenic dyslipidemia, and hypertension.1,2 Also, obesity is a well-established risk factor for the development of cardiovascular (CV) disorders (coronary artery disease, stroke, and myocardial infarction), which are leading causes of death.3 Adipose tissue stores energy, but the secretory products of adipocytes have been implicated in the pathogenesis of obesity-related metabolic disturbances. Namely, adipose tissue produces several bioactive peptides, known as adipocytokines, including leptin, tumor necrosis factor a, interleukin 6, adiponectin, and resistin.4 Proinflammatory and proatherogenic adipocytokines are involved in the development of insulin resistance, type 2 diabetes mellitus, and atherosclerosis.5 It has been shown that in obese patients with dysfunctional adipose tissue, leptin levels are elevated, while a reduction in caloric intake is accompanied by reduced leptin concentration.6 Additionally, it has been reported that resistin influences the occurrence of metabolic syndrome, a state characterized by metabolic, proinflammatory, and prothrombotic abnormalities.7-9 In contrast, adiponectin exerts protective actions against the metabolic and CV complications of obesity. Individuals with increased fat mass have low adiponectin levels, and it seems that adiponectin prevents further progression of insulin resistance and reduces the
progression of atherosclerosis.10 Subcutaneous and visceral adipose tissues manifest different morphological and functional characteristics. In this regard, dysfunctional changes in adipose tissue are particularly expressed in visceral fat depots.11,12 In recent years, there has been an increased interest in the other roles of vitamin D, in addition to those on the skeletal system. Serum concentrations of 25-hydroxyvitamin D, 25(OH)D, 38.4 kg/m2, our results demonstrated significant negative correlation between 25(OH)D and leptin serum levels (r ¼ -.61, P < .01). Leptin has been proposed to be involved in the energy homeostasis and insulin sensitivity modulation,30 also being positively associated with visceral adipose mass.31,32 Recent studies have revealed that serum levels of leptin are inversely associated with serum 25(OH)D,33 which is in agreement with our results. As a proinflammatory cytokine, resistin affects lipid metabolism, glucose tolerance, and may play a role in the pathogenesis of metabolic syndrome.34 The available data are dual with respect to its relation to vitamin D deficiency—our study noted a negative correlation of 25(OH)D with resistin serum levels (r ¼ -.6, P < .05), while in other investigations this relationship was not found.21,35 Negative correlation of leptin and resistin with 25(OH)D was statistically significant only in subgroup of patients with greater BMI. After considering the linear dependence and trend between 25(OH)D level and leptin and resistin, we found that they are at inverse dependence: with higher vitamin D levels, leptin and resistin have a downward trend. This is the case in all obese subgroups, whether they are above or below the anthropometric medians. In contrast to leptin and resistin, adiponectin exerts antiatherogenic, anti-inflammatory, and antiplatelet features.36 As such, its concentration is reduced in the presence of obesity, type 2 diabetes mellitus, and metabolic syndrome.37 Additionally, adiponectin serum levels have been positively associated with plasma 25(OH)D38,39; our results are in agreement with these findings. Namely, in the subgroup of patients with a higher degree of obesity, a significant positive correlation was noted between 25(OH)D and adiponectin levels (r ¼ .7, P < .001). The connection became clearer after the trend estimation, which has shown that vitamin D level increase is followed by ascending tendency of adiponectin levels. The intensive increase in adiponectin was established in the subgroup of BMI >38.4 kg/m2 with GC of 12.13. This finding may be of importance in the context of therapeutic options for vitamin D, since both the factors are implicated in the development of several cardiometabolic disturbances.17,40 Also, numerous previous studies proved that intra-abdominal obesity has a direct impact on increased CV risk due to the increased action of proinflammatory and proatherogenic cytokines.41,42 In our study, increase in adiponectin was also detected within the subgroups of patients who have larger WC and FAT trunk, with GCs of 4.3 and 4. This implies that
changes in abdominal fat mass have an impact on the 25(OH)D–adiponectin relation. In the view of present findings, we suggest that vitamin D supplementation may have a beneficial effect on obesity via modulation of adipocytokine secretions. Since the dysfunctional adipose tissue is a trigger for cardiometabolic disturbances in obese patients, interventional trials are required to establish whether vitamin D supplementation could be a therapeutic option for improving adipose tissue function and thus prevent obesity-related diseases.
Limitations We did not have specific information about sunlight exposure and vitamin D obtained from food. Additionally, the number of patients in our study was small. Finally, since our study is cross-sectional, causality cannot be determined. Authors’ Note This manuscript has not been published and is not being considered for publishing elsewhere, and it is not presented or submitted for international conferences, in any language. Edita Stokic´, Branka Kovacˇev-Zavisˇic´, and Esma Isenovic´ substantially contributed to concept and design. Aleksandar Kupusinac, Dragana Tomic´-Naglic´, and Dragana Smiljenic´ contributed to acquisition of data, analysis, and interpretation. Edita Stokic´, Biljana Srdic´-Galic´, and Dragana Smijenic´ contributed to drafting the article. Edita Stokic´, Sanja Soskic´, Esma Isenovic´, and Dragana Tomic´-Naglic´ contributed to final approval of the version to be published.
Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was partially supported by (grant numbers 174026, III044006, and 173033) the Ministry of Education, Science and Technological Development of the Republic of Serbia.
References 1. Must A, Strauss RS. Risks and consequences of childhood and adolescent obesity. Int J Obes Relat Metab Disord. 1999; 23(suppl 2):S2-S11. 2. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults—the evidence report. National institutes of health. Obes Res. 1998;6(suppl 2): 51S-209S. 3. WHO. Global health risk: mortality and burden of diseases attributable to selected major risks 2009. http://www.who.int/ healthinfo/global_burden_disease/GlobalHealthRisk_report_full. pdf. (Accessed on October 28, 2009) 4. Tomic´-Naglic´ D SE, Srdic´ B, Radovanov T. Masno tkivo kao endokrina zˇlezda. Medicina Danas. 2008;7(4-6):142-147. 5. Murdolo G, Smith U. The dysregulated adipose tissue: a connecting link between insulin resistance, type 2 diabetes mellitus and
Downloaded from ang.sagepub.com at COLUMBIA UNIV on August 18, 2014
Edita et al
6. 7.
8.
9.
10.
11.
12.
13.
14. 15.
16.
17.
18.
19.
20.
21.
5
atherosclerosis. Nutr Metab Cardiovasc Dis. 2006;16(suppl 1): S35-S38. Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab. 2004;89(6):2548-2556. Aquilante CL, Kosmiski LA, Knutsen SD, Zineh I. Relationship between plasma resistin concentrations, inflammatory chemokines, and components of the metabolic syndrome in adults. Metabolism. 2008;57(4):494-501. Ohmori R, Momiyama Y, Kato R, et al. Associations between serum resistin levels and insulin resistance, inflammation, and coronary artery disease. J Am Coll Cardiol. 2005;46(2): 379-380. Katsiki N, Athyros VG, Karagiannis A, Mikhailidis DP. Characteristics other than the diagnostic criteria associated with metabolic syndrome: an overview [published online April 25, 2013]. Curr Vasc Pharmacol. 2013. Koerner A, Kratzsch J, Kiess W. Adipocytokines: leptin—the classical, resistin—the controversial, adiponectin—the promising, and more to come. Best Pract Res Clin Endocrinol Metab. 2005;19(4):525-546. Misra A, Vikram NK. Clinical and pathophysiological consequences of abdominal adiposity and abdominal adipose tissue depots. Nutrition. 2003;19(5):457-466. Stokic´ E, Srdic´ Galic´ B, Tomic´-Naglic´ D, Isenovic´ E. Sagittal abdominal diameter (SAD) in identification obese patients of higher cardiovascular risk. Cardiology. 2013;126:169. Bischoff-Ferrari HA, Giovannucci E, Willett WC, Dietrich T, Dawson-Hughes B. Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr. 2006;84(1):18-28. Vanlint S. Vitamin D and obesity. Nutrients. 2013;5(3):949-956. 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):820-825. Scragg R, Sowers M, Bell C. Third National H, nutrition examination S. Serum 25-hydroxyvitamin D, diabetes, and ethnicity in the third national health and nutrition examination survey. Diabetes Care. 2004;27(12):2813-2818. Anderson JL, May HT, Horne BD, et al. Relation of vitamin D deficiency to cardiovascular risk factors, disease status, and incident events in a general healthcare population. Am J Cardiol. 2010;106(7):963-968. Earthman CP, Beckman LM, Masodkar K, Sibley SD. The link between obesity and low circulating 25-hydroxyvitamin D concentrations: considerations and implications. Int J Obes (Lond). 2012;36(3):387-396. Stokic E, Kupusinac A, Tomic-Naglic D, et al. Obesity and vitamin D deficiency: trends to promote a more proatherogenic cardiometabolic risk profile [published online March 21, 2014]. Angiology. 2014. Need AG, O’Loughlin PD, Horowitz M, Nordin BE. Relationship between fasting serum glucose, age, body mass index and serum 25 hydroxyvitamin D in postmenopausal women. Clin Endocrinol (Oxf). 2005;62(6):738-741. Vilarrasa N, Vendrell J, Maravall J, et al. Is plasma 25(OH)D related to adipokines, inflammatory cytokines and insulin
22.
23.
24.
25.
26. 27. 28.
29.
30.
31.
32.
33.
34.
35.
36.
37. 38.
resistance in both a healthy and morbidly obese population? Endocrine. 2010;38(2):235-242. Kempt Am SM, Li C, Kaur H, Huang Tt. Leptin is a maker of body fat and hyperinsulinemia in college students. J Am Coll Nutr. 2006;55(3):175-180. Kim M, Na W, Sohn C. Correlation between vitamin D and cardiovascular disease predictors in overweight and obese Koreans. J Clin Biochem Nutr. 2013;52(2):167-171. Liu E, Meigs JB, Pittas AG, et al. Plasma 25-hydroxyvitamin D is associated with markers of the insulin resistant phenotype in nondiabetic adults. J Nutr. 2009;139(2):329-334. Al-Daghri NM, Al-Attas OS, Alokail MS, et al. Hypovitaminosis D associations with adverse metabolic parameters are accentuated in patients with type 2 diabetes mellitus: a body mass indexindependent role of adiponectin? J Endocrinol Invest. 2013; 36(1):1-6. Lips P. Worldwide status of vitamin D nutrition. J Steroid Biochem Mol Biol. 2010;121(1-2):297-300. Liel Y, Ulmer E, Shary J, Hollis BW, Bell NH. Low circulating vitamin D in obesity. Calcif Tissue Int. 1988;43(4):199-201. Hyldstrup L, Andersen T, Mcnair P, Breum L, Transbol I. Bone metabolism in obesity: changes related to severe overweight and dietary weight reduction. Acta Endocrinol (Copenh). 1993; 129(5):393-398. Wortsman J, Matsuoka LY, Chen TC, Lu Z, Holick MF. Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr. 2000;72(3):690-693. Kong J, Chen Y, Zhu G, Zhao Q, Li YC. 1,25-Dihydroxyvitamin D3 upregulates leptin expression in mouse adipose tissue. J Endocrinol. 2013;216(2):265-271. Indulekha K, Anjana RM, Surendar J, Mohan V. Association of visceral and subcutaneous fat with glucose intolerance, insulin resistance, adipocytokines and inflammatory markers in Asian Indians (CURES-113). Clin Biochem. 2011;44(4):281-287. Ding C, Parameswaran V, Cicuttini F, et al. Association between leptin, body composition, sex and knee cartilage morphology in older adults: the Tasmanian older adult cohort (TASOAC) study. Ann Rheum Dis. 2008;67(9):1254-1256. Maetani M, Maskarinec G, Franke AA, Cooney RV. Association of leptin, 25-hydroxyvitamin D, and parathyroid hormone in women. Nutr Cancer. 2009;61(2):225-231. Abate N, Sallam HS, Rizzo M, et al. Resistin: an inflammatory cytokine. Role in cardiovascular diseases, diabetes and the metabolic syndrome [published online December 5, 2013]. Curr Pharm Des. 2013. Roth CL, Elfers C, Kratz M, Hoofnagle AN. Vitamin D deficiency in obese children and its relationship to insulin resistance and adipokines. J Obes. 2011;2011:495101. Ohashi K, Ouchi N, Matsuzawa Y. Anti-inflammatory and antiatherogenic properties of adiponectin. Biochimie. 2012;94(10): 2137-2142. Scherer PE. Adipose tissue: from lipid storage compartment to endocrine organ. Diabetes. 2006;55(6):1537-1545. Nimitphong H, Chanprasertyothin S, Jongjaroenprasert W, Ongphiphadhanakul B. The association between vitamin D status and circulating adiponectin independent of adiposity in subjects
Downloaded from ang.sagepub.com at COLUMBIA UNIV on August 18, 2014
6
Angiology
with abnormal glucose tolerance. Endocrine. 2009;36(2): 205-210. 39. Roth CL, Kratz M, Ralston MM, Reinehr T. Changes in adiposederived inflammatory cytokines and chemokines after successful lifestyle intervention in obese children. Metabolism. 2011;60(4): 445-452. 40. Vaidya A, Williams JS, Forman JP. The independent association between 25-hydroxyvitamin D and adiponectin and its relation
with BMI in two large cohorts: the NHS and the HPFS. Obesity (Silver Spring). 2012;20(1):186-191. 41. Kupusinac A SE, Srdic´ Galic´ B. Determination of WHtR limit for predicting hyperglycemia in obese persons by using artificial neural networks. TEM J. 2012;1(4):270-272. 42. Stokic´ E, Kupusinac A, Doroslovacˇki R. Estimating SAD lowlimits for the adverse metabolic profile by using artificial neural networks. TEM J. 2013(2):115-119.
Downloaded from ang.sagepub.com at COLUMBIA UNIV on August 18, 2014
