Role of Vitamin D in Premature Atherosclerosis in Adolescents Type 1 Diabetes through Transforming Growth Factor-β1, Interferon-γ, Interleukin-10, and Interleukin-17

Authors

  • Haryudi Aji Cahyono Doctoral Program of Medical Science, Faculty of Medicine Universitas Brawijaya, Malang, Indonesia; Saiful Anwar Hospital, Malang, Indonesia; Department of Pediatric, Faculty of Medicine Universitas, Brawijaya, Malang, Indonesia
  • Wisnu Barlianto Saiful Anwar Hospital, Malang, Indonesia; Department of Pediatric, Faculty of Medicine Universitas, Brawijaya, Malang, Indonesia
  • Dian Handayani Nutrition Science Program, Medical Faculty, Universitas Brawijaya, Malang, Indonesia
  • Handono Kalim Department of Internal Medicine, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia

DOI:

https://doi.org/10.3889/oamjms.2020.4619

Keywords:

Cytokine, Premature atherosclerosis, Type 1 diabetes, Vitamin D

Abstract

BACKGROUND: Cardiovascular disease (CVD) is one the cause of mortality in patients with type 1 diabetes (T1D). The development of CVD is mainly triggered by atherosclerosis, which is associated with the inflammatory process.

AIM: The current study was aimed to investigate the association of Vitamin D level and premature atherosclerosis in adolescents with T1D, mainly through the regulation of various cytokines (interferon-γ [IFN-γ], IL-17, interleukin-10 [IL-10], and transforming growth factor-β1 [TGF-β1]).

METHODS: This study was designed as a cross-sectional study involving 40 T1D and 40 healthy control who came to the outpatient clinic, Saiful Anwar Hospital, Malang, Indonesia, within the study period (January 2019-July 2019).

RESULTS: Our data demonstrated that the IFN-γ and IL-17 levels were significantly higher (p < 0.001), whereas the TGF-β1 and IL-10 levels were significantly lower (p < 0.001) in T1D group compared with control. Furthermore, T1D also has higher carotid intima-media thickness (cIMT) value and lower flow-mediated dilatation (FMD) value compared to the control group (p < 0.001). Level of 25(OH)D3 was strongly associated with reduced cIMT and elevated FMD (p < 0.005). The direct effect of 25(OH)D3 on cIMT and FMD was higher than the indirect effect of Vitamin D through TGF-β1, IL-10, IL-17, and IFN-γ. The cutoff value of 25(OH)D3 levels for the risk of atherosclerosis was 12.8 ng/dL (sensitivity 85.7% and specificity 86.7%).

CONCLUSION: The level of Vitamin D in the T1D group was significantly lower than those in healthy children and Vitamin D deficiency substantially influences the formation of premature atherosclerosis.

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References

International Diabetes Foundation. Diabetes atlas. 6th ed. Vol. 6. International Diabetes Foundation; 2017. p. 142-5.

Kemenkes Republik Indonesia. Hasil Utama Riset Kesehatan Dasar Tahun. Indonesia: Kementrian Kesehatan Republik Indonesia; 2018. https://doi.org/10.6066/jtip.2013.24.2.121

Hoffman RP. Vascular endothelial dysfunction and nutritional compounds in early Type 1 diabetes. Curr Diabetes Rev 2014;10(3):201-7. https://doi.org/10.2174/15733998106661406 13124326 PMid:24925525

Lee SI, Patel M, Jones CM, Narendran P. Cardiovascular disease and Type 1 diabetes: Prevalence, prediction and management in an ageing population. Ther Adv Chronic Dis 2015;6(6):347-74. PMid:26568811

Krantz JS, Mack WJ, Hodis HN, Liu CR, Kaufman FR. Early onset of subclinical atherosclerosis in young persons with Type 1 diabetes. J Pediatr 2004;145(4):452-7. https://doi.org/10.1016/j.jpeds.2004.06.042 PMid:15480366

Purnell JQ, Zinman B, Brunzell JD; DCCT/EDIC Research Group. The effect of excess weight gain with intensive diabetes mellitus treatment on cardiovascular disease risk factors and atherosclerosis in Type 1 diabetes mellitus: Results from the diabetes control and complications trial/epidemiology of diabetes interventions and complications study (DCCT/EDIC) study. Circulation 2013;127(2):180-7. https://doi.org/10.1161/ circulationaha.111.077487 PMid:23212717

Muis MJ, Bots ML, Bilo HJ, Hoogma RP, Hoekstra JB, Grobbee DE, et al. High cumulative insulin exposure: A risk factor of atherosclerosis in Type 1 diabetes? Atherosclerosis 2005;181(1):185-92. https://doi.org/10.1016/j. atherosclerosis.2005.01.004 PMid:15939071

Dahl-Jørgensen K, Larsen JR, Hanssen KF. Atherosclerosis in childhood and adolescent Type 1 diabetes: Early disease, early treatment? Diabetologia 2005;48(8):1445-53. https://doi. org/10.1007/s00125-005-1832-1 PMid:15971059

Hernández M, López C, Real J, Valls J, de Victoria EO, Vazquez F, et al. Preclinical carotid atherosclerosis in patients with latent autoimmune diabetes in adults (LADA), Type 2 diabetes and classical type 1 diabetes. Cardiovasc Diabetol 2017;16(1):94. https://doi.org/10.1186/s12933-017-0576-9 PMid:28750634

Frismantiene A, Pfaff D, Frachet A, Coen M, Joshi MB, Maslova K, et al. Regulation of contractile signaling and matrix remodeling by T-cadherin in vascular smooth muscle cells: Constitutive and insulin-dependent effects. Cell Signal 2014;26(9):1897-908. https://doi.org/10.1016/j.cellsig.2014.05.001 PMid:24815187

Bauer M, Caviezel S, Teynor A, Erbel R, Mahabadi A, Schmidt- Trucksass A. Carotid intima-media thickness as a biomarker of subclinical atherosclerosis. Swiss Med Wkly 2012;142:w13705. https://doi.org/10.4414/smw.2012.13705 PMid:23135891

Bartels S, Franco AR, Rundek T. Carotid intima-media thickness (cIMT) and plaque from risk assessment and clinical use to genetic discoveries. Perspect Med 2012;1(1-12):139-45. https:// doi.org/10.1016/j.permed.2012.01.006

Den Ruijter HM, Peters SA, Anderson TJ, Britton AR, Dekker JM, Eijkemans MJ, et al. Common carotid intima-media thickness measurements in cardiovascular risk prediction: A meta-analysis. JAMA 2012;308(8):796-803. https://doi.org/10.1016/j. jvs.2012.10.058 PMid:22910757

Simon A, Megnien JL, Chironi G. The value of carotid intima-media thickness for predicting cardiovascular risk. Arterioscler Thromb Vasc Biol 2010;30(2):182-5. https://doi.org/10.1161/ atvbaha.109.196980 PMid:19948842

Norman PE, Powell JT. Vitamin D and cardiovascular disease. Circulation Res 2014;114(2):379-93. PMid:22689009

Apostolakis M, Armeni E, Bakas P, Lambrinoudaki I. Vitamin D and cardiovascular disease. Maturitas 2018;115:1-22. https:// doi.org/10.1016/j.maturitas.2018.05.010 PMid:30049340

van Schoor NM, Lips P. Worldwide Vitamin D status. Best Pract Res Clin Endocrinol Metab 2011;25(4):671-80. PMid:21872807

Santoro D, Caccamo D, Lucisano S. Interplay of Vitamin D, erythropoiesis, and the renin-angiotensin system. Biomed Res Int 2015;2015:145828. https://doi.org/10.1155/2015/145828 PMid:26000281

DiMeglio LA, Evans-Molina C, Oram RA. Type 1 diabetes. Lancet 2018;391(10138):2449-62. https://doi.org/10.1016/ s0140-6736(18)31320-5 PMid:29916386

Taleb S, Tedgui A, Mallat Z. IL-17 and Th17 cells in atherosclerosis: Subtle and contextual roles. Arterioscler Thromb Vasc Biol 2015;35(2):258-64. https://doi.org/10.1161/ atvbaha.114.303567 PMid:25234818

McLaren JE, Ramji DP. Interferon gamma: a master regulator of atherosclerosis. Cytokine Growth Factor Rrev. 2009;20(2):125- 35. http://doi.org/10.1016/j.cytogfr.2008.11.003 PMid: 19041276

Delic-Sarac M, Mutevelic S, Karamethic J, Subasic D, Jukic T, Ridjic O, et al. ELISA test for analyzing of incidence of type 1 diabetes autoantibodies (GAD and IA2) in children and adolescents. Acta Inform Med 2016;24(1):61-5. https://doi. org/10.5455/aim.2016.24.61-65 PMid:27041813

Chen LJ, Lim SH, Yeh YT, Lien SC, Chiu JJ. Roles of microRNAs in atherosclerosis and restenosis. J Biomed Sci.2012;19(1):79. https://doi.org/10.1186/1423-0127-19-79 PMid:22931291

Toma I, McCaffrey TA. Transforming growth factor-β and atherosclerosis: Interwoven atherogenic and atheroprotective aspects. Cell Tissue Res. 2012;347(1):155-75. https://doi. org/10.1007/s00441-011-1189-3 PMid:21626289

Hoving LR, Katiraei S, Heijink M, Pronk A, van der Wee-Pals L, Streefland T, et al. Dietary mannan oligosaccharides modulate gut microbiota, increase fecal bile acid excretion, and decrease plasma cholesterol and atherosclerosis development. Mol Nutr Food Res 2018;62(10):e1700942. https://doi.org/10.1002/ mnfr.201700942 PMid:29665623

Taylor AJ, Sullenberger LE, Lee HJ, Lee JK, Grace KA. Arterial biology for the investigation of the treatment effects of reducing cholesterol (ARBITER) 2: A double-blind, placebo-controlled study of extended-release niacin on atherosclerosis progression in secondary prevention patients treated with statins. Circulation 2004;110(23):3512-7. https://doi.org/10.1161/01. cir.0000148955.19792.8d PMid:15537681

Cabrera SM, Henschel AM, Hessner MJ. Innate inflammation in Type 1 diabetes. Transl Res 2016;167(1):214-27. https://doi. org/10.1016/j.trsl.2015.04.011 PMid:25980926

Bijjiga E, Martino A. Interleukin 10 (IL-10) regulatory cytokine and its clinical consequences. J Clin Cell Immunol 2013;S1:7. https://doi.org/10.4172/2155-9899.s1-007

Cutolo M, Paolino S, Sulli A, Smith V, Pizzorni C, Seriolo B. Vitamin D, steroid hormones, and autoimmunity. Ann N Y Acad Sci 2014;1317:39-46. https://doi.org/10.1111/nyas.12432 PMid:24739090

Ammirati E, Moroni F, Norata GD, Magnoni M, Camici PG. Markers of inflammation associated with plaque progression and instability in patients with carotid atherosclerosis. Mediators Inflamm 2015;2015:718329. https://doi. org/10.1155/2015/718329 PMid:25960621

Atwa HA, Shora HA, Elsayed A. Hormonal, metabolic and radiological markers of subclinical atherosclerosis in Egyptian children with Type 1 diabetes. Rep Endocr Disord 2018;2(1):3.

Trigona B, Aggoun Y, Maggio A, Martin XE, Marchand LM, Beghetti M, et al. Preclinical noninvasive markers of atherosclerosis in children and adolescents with Type 1 diabetes are influenced by physical activity. J Pediatr 2010;157(4):533-9. https://doi.org/10.1016/j.jpeds.2010.04.023 PMid:20826281

Kamaly N, Fredman G, Fojas JJ, Subramanian M, Choi WI, Zepeda K, et al. Targeted interleukin-10 nanotherapeutics developed with a microfluidic chip enhance resolution of inflammation in advanced atherosclerosis. ACS Nano 2016;10(5):5280-92. https://doi.org/10.1021/acsnano.6b01114 PMid:27100066

Ait-Oufella H, Taleb S, Mallat Z, Tedgui A. Recent advances on the role of cytokines in atherosclerosis. Arterioscler Thromb Vasc Biol 2011;31(5):969-79. https://doi.org/10.1161/ atvbaha.110.207415 PMid:21508343

Tedgui A, Mallat Z. Cytokines in atherosclerosis: Pathogenic and regulatory pathways. Physiol Rev 2006;86(2):515-81. https://doi.org/10.1152/physrev.00024.2005 PMid:16601268

Ross R. Atherosclerosis an inflammatory disease. N Eng J Med 1999;340(2):115-26. PMid:22390643

Ryu H, Chung Y. Regulation of IL-17 in atherosclerosis and related autoimmunity. Cytokine 2015;74(2):219-27. https://doi. org/10.1016/j.cyto.2015.03.009 PMid:25890878

Allam G, Abdel-Moneim A, Gaber AM. The pleiotropic role of interleukin-17 in atherosclerosis. Biomed Pharmacother 2018;106:1412-18. https://doi.org/10.1016/j.biopha.2018.07.110 PMid:30119214

Major AS, Harrison DG. What fans the fire: Insights into mechanisms of inflammation in atherosclerosis and diabetes mellitus. Circulation 2011;124(25):280911. https://doi. org/10.1161/circulationaha.111.070565 PMid:22184043

Tiwari S, Pratyush DD, Gupta SK, Singh SK. Vitamin D deficiency is associated with inflammatory cytokine concentrations in patients with diabetic foot infection. Br J Nutr 2014;112(12):1938- 43. https://doi.org/10.1017/s0007114514003018 PMid:25331710

Carrelli AL, Walker MD, Lowe H, McMahon DJ, Rundek T, Sacco RL, et al. Vitamin D deficiency is associated with subclinical carotid atherosclerosis: The Northern Manhattan study. Stroke 2011;42(8):2240-5. https://doi.org/10.1161/ strokeaha.110.608539 PMid:21719770

Devaraj S, Yun JM, Duncan-Staley CR, Jialal I. Low Vitamin D levels correlate with the proinflammatory state in Type 1 diabetic subjects with and without microvascular complications. Am J Clin Pathol 2011;135(3):429-33. https://doi.org/10.1309/ ajcpjgzqx42biaxl PMid:21350098

Young KA, Snell-Bergeon JK, Naik RG, Hokanson JE, Tarullo D, Gottlieb PA, et al. Vitamin D deficiency and coronary artery calcification in subjects with Type 1 diabetes. Diabetes Care 2011;34(2):454-8. https://doi.org/10.2337/dc10-0757 PMid:20978098

Sachs MC, Brunzell JD, Cleary PA, Hoofnagle AN, Lachin JM, Molitch ME, et al. Circulating Vitamin D metabolites and subclinical atherosclerosis in Type 1 diabetes. Diabetes Care 2013;36(8):2423-9. https://doi.org/10.2337/dc12-2020 PMid:23530012

Bilir B, Tulubas F, Bilir BE, Atile NS, Kara SP, Yildirim T, et al. The association of Vitamin D with inflammatory cytokines in diabetic peripheral neuropathy. J Phys Ther Sci 2016;28(7):2159-63. https://doi.org/10.1589/jpts.28.2159 PMid:27512288

Wulandari D, Cahyono HA, Widjajanto E, Puryatni A. Low levels of Vitamin D correlate with hemoglobin A1c and interleukin-10 levels in pediatric Type 1 diabetes mellitus patients. J Trop Life Sci 2014;4(3):182-6. https://doi.org/ 10.11594/jtls.04.03.04

Ren Z, Li W, Zhao Q, Ma L, Zhu J. The impact of 1,25-dihydroxy vitamin D3 on the expressions of vascular endothelial growth factor and transforming growth factor-β1 in the retinas of rats with diabetes. Diabetes Res Clin Pract 2012;98(3):474-80. https://doi.org/10.1016/j.diabres.2012.09.028 PMid:23089551

Geovanini GR, Libby P. Atherosclerosis and inflammation: Overview and updates. Clin Sci (London). 2018;132(12):1243- 52. https://doi.org/10.1042/cs20180306

Pillay AK, Naidoo DP. Atherosclerotic disease is the predominant aetiology of acute coronary syndrome in young adults. Cardiovasc J Afr 2018;29(1):36-42. https://doi.org/10.5830/ cvja-2017-035 PMid:29930142

Dalla Pozza R, Beyerlein A, Thilmany C, Weissenbacher C, Netz H, Schmidt H, et al. The effect of cardiovascular risk factors on the longitudinal evolution of the carotid intima medial thickness in children with Type 1 diabetes mellitus. Cardiovasc Diabetol 2011;10:53. https://doi.org/10.1186/1475-2840-10-53 PMid:21679428

Yang SN, Burch ML, Tannock LR, Evanko S, Osman N, Little PJ. Transforming growth factor‐β regulation of proteoglycan synthesis in vascular smooth muscle: Contribution to lipid binding and accelerated atherosclerosis in diabetes. J Diabetes. 2010;2(4):233- 42. https://doi.org/10.1111/j.1753-0407.2010.00089.x PMid:20923499

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Published

2020-08-15

How to Cite

1.
Cahyono HA, Barlianto W, Handayani D, Kalim H. Role of Vitamin D in Premature Atherosclerosis in Adolescents Type 1 Diabetes through Transforming Growth Factor-β1, Interferon-γ, Interleukin-10, and Interleukin-17. Open Access Maced J Med Sci [Internet]. 2020 Aug. 15 [cited 2024 Apr. 23];8(B):738-46. Available from: https://oamjms.eu/index.php/mjms/article/view/4619

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