Levels of 25(OH)D3, IL-2, and C-peptide in Children with Type 1 Diabetes Mellitus (T1DM) Receiving Vitamin D3 Supplementation

Tjahyo Suryanto, Harjoedi Adji Tjahjono, Edi Widjajanto

Abstract


Type 1 Diabetes Mellitus (T1DM) has become a health problem in many countries. T1DM is the consequence of autoimmune destruction process of β cells. There was relationship between vitamin D deficiency with T1DM. The destruction process was caused by an imbalance of pro-inflammatory and anti-inflammatory cytokines. One of the pro-inflammatory cytokines is IL-2. C-peptide examination to see the function of beta cells due to destruction of pancreatic beta cell. Administration of vitamin D3 supplementation still cause controversy and give varying results. This randomized clinical trial was conducted to determine the levels of 25(OH)D3, IL-2, and C-peptide in people with T1DM who received vitamin D3 supplementation. The subjects were 26 children with T1DM, divided into K1 group (received vitamin D3 supplementation) and K2 group (received placebo). The results showed higher levels of 25(OH)D3 in the K1 group and statistically found a significant difference (p = 0.00). Higher levels of IL-2 and lower C-peptide were obtained in the K1 group and no statistically significant differences were found (p = 0.76 and p= 0.26). The insignificant relationship and the negative correlation were found between 25(OH)D3 and IL-2 (p = 0.71; r = - 0.12), 25(OH)D3 and C-peptide (p = 0.59; r = -0.16), also levels of IL-2 and C-peptide (p = 0.13; r = -0.44) in children with type 1 diabetes who received vitamin D3 supplementation. From this study can be concluded that administration vitamin D3 supplementation in patients with T1DM can increase levels 25(OH)D3 significantly. This increase has not significantly lowered levels of IL-2 and increased levels of C-peptide. However, there was an absolute decrease in the rate of slower C-peptide in the supplemented group than in the placebo group.

Keywords


Type 1 DM, 25(OH)D3, C-peptide, IL-2

Full Text:

PDF

References


Craig ME, Jefferies C, Dabelea D et al. (2014) Definition, epidemiology, and classification of diabetes in children and adolescents. Pediatric Diabetes 15 (20): 4 – 17. doi: 10.1111/pedi.12186.

Himawan IW, Pulungan AB, Tridjaja B, Batubara JRL, (2012) Gambaran diabetes melitus tipe 1 di Indonesia. Sari Pediatri 15 (6): 57 – 62. doi: 10.14238/sp13.5.2012.367-72.

Cahyono HA (2013) Gambaran klinis dan laboratoris diabetes melitus tipe-1 pada anak. Jurnal Kedokteran Brawijaya. 26 (4): 195 – 198. doi: 10.21776/ub.jkb.2011.026.04.2.

Rajashree R, Ravishankar MV, Kholkute SD, Goudar SS (2012) Type 1 diabetes mellitus: An update. International Journal of Diabetes and Metabolism 20 (3): 37 – 42.

Jeker LT, Bour-Jourdan H, Bluestone JA (2012) Break-down in peripheral tolerance in type 1 diabetes in mice and humans. Cold Spring Harbor Perspectives in Medi-cine 12 (2): 78 – 93. doi: 10.1101/cshperspect.a007807.

Mathieu C, Badenhoop K (2005) Vitamin D and type 1 diabetes mellitus: State of the art. Trends in Endocrinology and Metabolism 16 (6): 261 – 266. doi: 10.1016/j.tem.2005.06.004.

Craig ME, Hattersley A, Donaghue KC (2009) Definition, epidemiology and classification of diabetes in children and adolescents. Pediatric Diabetes 10 (12): 3 – 12. doi: 10.1111/j.1399-5448.2009.00568.x.

Hulme MA, Wasserfall CH, Atkinson MA, Brusko TM (2012) Central Role for Interleukin-2 in Type 1 Diabetes. Diabetes 61 (14): 14 – 22. doi: 10.2337/db11-1213.

Palmer JP, Fleming GA, Greenbaum CJ et al. (2004) C-peptide is the appropriate outcome measure for type 1 dia-betes clinical trials to preserve beta-cell function: Report of an ADA workshop. Diabetes 53 (1): 250 – 264. doi: 10.2337/diabetes.53.1.250.

Jones AG, Hattersley AT (2013) The Clinical Utility of C-peptide Measurement in the Care of Patients with Diabe-tes. Diabetic Medicine 30 (7): 803 – 817. doi: 10.1111/dme.12159.

Svoren BM, Volkening LK, Wood JR, Laffel LMB (2009) Significant vitamin D deficiency in youth with type 1 diabe-tes mellitus. The Journal of Pediatrics 154 (1): 132 – 134. doi: 10.1016/j.jpeds.2008.07.015.

Janner M, Ballinari P, Mullis PE, Fluck CE (2010) High prevalence of vitamin D deficiency in children and adoles-cent with type 1 diabetes. Swiss Medical Weekly 140 (7): 1 – 6. doi: 10.4414/smw.2010.13091.

Greer RM, Portelli L, Hung BS et al. (2013) Serum vitamin D levels are lower in Australian children and adolescents with type 1 diabetes than in children without diabetes. Pe-diatric Diabetes 14 (1): 31 – 41. doi: 10.1111/j.1399-5448.2012.00890.x.

Wulandari D, Cahyono HA, Widjajanto E, Puryatni A (2014) Low levels of vitamin D correlate with hemoglobin a1c and interleukin-10 levels in pediatric type 1 diabetes mellitus patients. Journal of Tropical Life Science 4 (3): 182 – 186. doi: 10.11594/jtls.04.03.04.

Chakhtoura M, Azar ST (2013) The role of vitamin D deficiency in the incidence, progression, and complica-tions of type 1 diabetes mellitus. International Journal of Endocrinology 2013 (2013): 1 – 10. doi: 10.1155/2013/148673.

Harinarayan CV (2014) Vitamin D and diabetes mellitus. Hormones 13 (2): 163 – 181.

Prietl B, Pilz S, Wolf M, Tomaschitz A et al. (2010) Vita-min D supplementation and regulatory t cells in apparently healthy subjects: Vitamin D treatment for autoimmune dis-eases?. Israel Medical Association Journal 12 (3): 136 – 139.

Pulungan AB, Mansyoer R, Batubara JRL, Tridjaja B (2002) Gambaran klinis dan laboratoris diabetes mellitus tipe-1 pada anak saat pertama kali datang ke bagian IKA-RSCM Jakarta. Sari Pediatri 4 (1): 26 – 30. doi: 10.14238/sp4.1.2002.26-30.

Endyarni B, Batubara JRL, Boediman I (2006) Effects of a structured educational intervention on metabolic control of type-1 diabetes mellitus patients. Paediatrica Indonesia 46 (11 – 12): 260 – 265. doi: 10.14238/pi46.6.2006.260-5.

da Costa VM, de Carvalho Padilha P, de Lima GCF et al. (2016) Overweight among children and adolescent with type I diabetes mellitus: Prevalence and associated factors. Diabetology and Metabolic Syndrome 8 (39): 1 – 6. doi: 10.1186/s13098-016-0154-4.

Hassanein MA, Sultan I (2014) Evaluation of nutrition and health status among children with diabetes. Life Science Journal 11 (2): 327 – 334.

Pulungan AB (2010) Pubertas dan gangguannya. In: Batu-bara JRL, Tridjaja B, Pulungan AB, eds. Buku ajar en-dokrinologi anak. Jakarta, Sagung Seto. pp 85 – 120.

Tfayli H, Arslanian S (2007) The challenge of adolescence: hormonal changes and sensitivity to insulin. Diabetes Voice 52 (Special Issue): 28 – 30.

Himawan IW, Pulungan AB, Tridjaja B, Batubara JRL (2009) Komplikasi jangka panjang dan jangka pendek dia-betes melitus tipe 1. Sari Pediatri 10 (6): 367 – 372. doi: 10.14238/sp10.6.2009.367-72.

Haller MJ, Wasserfall CH, Hulme MA et al. (2013) Autol-ogous umbilical cord blood infusion followed by oral do-cosahexaenoic acid and vitamin d supplementation for C-peptide preservation in children with type 1 diabetes. Biol-ogy of Blood and Marrow Transplantation 19 (7): 1124 – 1135. doi: 10.1016/j.bbmt.2013.04.011.

Federico G, Focosi D, Marchi B et al. (2014) Administer-ing 25-hydroxyvitamin D3 in vitamin D-deficient young type 1A diabetic patients reduces reactivity against islet au-toantigens. Clinical Nutrition 33 (6): 1153 – 1156. doi: 10.1016/j.clnu.2014.01.001.

Chandler PD, Giovannucci EL, Scott JB et al. (2014) Effects of vitamin D supplementation on C-peptide and 25-hydroxyvitamin D concentrations at 3 and 6 months. Scien-tific Reports 5 (10411): 1 – 10. doi: 10.1038/srep10411.

Savastio S, Cadario F, Genoni G et al. (2016) Vitamin D deficiency and glycemic status in children and adolescents with type 1 diabetes mellitus. PLoS ONE 11 (9): e0162554. 10.1371/journal.pone.0162554.

Dayal D, Sachdeva N (2015) Preservation of residual beta cell function with vitamin D supplementation in type 1 di-abetes. Immunoendocrinology 2 (2015): e1093. doi: 10.14800/ie.1093

Gabbay MAL, Sato MN, Finazzo C et al. (2012) Effect of cholecalciferol as adjunctive therapy with insulin on pro-tective immunologic profile and decline of residual β-cell function in new-onset type 1 diabetes mellitus. Archives of Pediatrics and Adolescent Medicine 166 (7): 601 – 607. doi:10.1001/archpediatrics.2012.164.

Walter M, Kaupper T, Adler K et al. (2010) No effect of the 1 alpha, 25-dihydroxyvitamin d3 on beta cell residual function and insulin requirement in adults with new onset type 1 diabetes. Diabetes Care 33 (7): 1443 – 1448. doi: 10.2337/dc09-2297.

Bizzarri C, Pitocco D, Napoli N et al. (2010) No protective effect of calcitriol on β-cell function in recent-onset type 1 diabetes. Diabetes Care 33 (9): 1962 – 1963. doi: 10.2337/dc10-0814.

Li X, Liao L, Yan X et al. (2009) Protective effects of 1-alpha-hydroxyvitamin d3 on residual beta-cell function in patients with Adult-onset Latent Autoimmune Diabetes (LADA). Diabetes/Metabolism Research and Reviews 25 (5): 411 – 416. doi: 10.1002/dmrr.977.

Ataie-Jafari A, Loke SC, Rahmat AB et al. (2013) A ran-domized placebo-controlled trial of alphacalcidol on the preservation of beta cell function in children with recent onset type 1 diabetes. Clinical Nutrition 32 (6): 911 – 917. doi: 10.1016/j.clnu.2013.01.012.

Chen S, Sims GP, Chen XX et al. (2007) Modulatory ef-fects of 1,25-dihydroxyvitamin D3 on human D cell differ-entiation. The Journal of Immunology 179 (7): 1634 – 1647. doi: 10.4049/jimmunol.179.3.1634.

Jeffery LE, Burke F, Mura M et al. (2009) 1,25-dihydroxyvitamin D3 and interleukin-2 combine to inhibit t cell production of inflammatory cytokines and promote development of regulatory T cells expressing CTLA-4 and FoxP3. The Journal of Immunology 183 (9): 5458 – 5467. doi: 10.4049/jimmunol.0803217.

Jeffery LE, Qureshi OS, Gardner D et al. (2015) Vitamin D antagonises the suppressive effect of inflammatory cyto-kines on CTLA-4 expression and regulatory function. PLoS ONE 10 (7): 1 – 18. doi: 10.1371/journal.pone.0131539.

Almeida MH, Dantas JR, Barone B et al. (2013) Residual C-peptide in patients with type 1 diabetes and multiethnic backgrounds. Clinics 68 (1): 123 – 126. doi: 10.6061/clinics/2013(01)RC02.

Wang L, Lovejoy NF, Faustman DL (2012) Persistence of prolonged C-peptide production in type 1 diabetes as measured with an ultrasensitive C-peptide assay. Diabetes Care 35 (3): 465 – 470. doi: 10.2337/dc11-1236.

Overbergh L, Decallonne B, Waer M et al. (2000) 1alpha,25- dihydroxyvitamin D3 induces an autoantigen-specific T-helper 1/T-helper 2 immune shift in NOD mice immunized with GAD65. Diabetes 49 (24): 1301 – 1307. doi: 10.2337/diabetes.49.8.1301.

Setoguchi R, Hori S, Takahashi T, Sakaguchi S (2005) Homeostatic maintenance of natural Foxp3+ CD25+ CD4+ regulatory T cells by interleukin (IL)-2 and induction of autoimmune disease by IL-2 neutralization. The Journal of Experimental Medicine 201 (5): 723 – 735. doi: 10.1084/jem.20041982.

Thornton AM, Donovan EE, Piccirillo CA, Shevach EM (2004) Cutting edge: IL-2 is critically required for the in vitro activation of CD4 +CD25+ T cell suppressor function. The Journal of Immunology 172 (11): 6519 – 6523. doi: 10.4049/jimmunol.172.11.6519.

Malek TR, Bayer AL (2004) Tolerance, not immunity, crucially depends on IL-2. Nature Reviews Immunology 4: 665 – 674. doi:10.1038/nri1435.

Dragović T, Raden S, Djurović B, Rabrenović V (2016) Extraskeletal activity of vitamin D and a potential associa-tion with diabetes mellitus. Vojnosanitetski Pregled 74 (5): 476 – 482. doi: 10.2298/VSP151011114D.

van Belle TI, Coppieters KT, von Herrath MG (2011) Type 1 diabetes: Etiology, immunology and therapeutic strate-gies. Physiological Reviews 91 (1): 79 – 118. doi: 10.1152/physrev.00003.2010.




DOI: http://dx.doi.org/10.11594/jtls.08.01.06

Copyright (c) 2018 Journal of Tropical Life Science