Effect of Vitamin D3 Supplementation to 25(OH)D, IL-17, and HbA1c Level in Pediatric Type 1 Diabetes Mellitus

Authors

  • Rahmah Yasinta Rangkuti Brawijaya University
  • Harjoedi Adji Tjahjono Brawijaya University

DOI:

https://doi.org/10.11594/jtls.07.01.06

Keywords:

25(OH)D, HbA1c, IL-17, type 1 diabetes mellitus, vitamin D

Abstract

Type 1 Diabetes Mellitus (T1DM) is the consequence of autoimmune destruction process of β cells which associated with Th17 activity and low 25(OH)D level. This study was aimed to investigate the effect of vitamin D3 supplementation toward 25(OH)D level, Th17 activity (IL-17) and glycemic control (HbA1c) in pediatric T1DM. This study was designed as randomized clinical trials (RCT), double-blind, pre and post-test controlled study. Subject was children with T1DM who were divided into two groups: K1: subjects were treated with insulin 0.5–2 IU/day + vitamin D3 2000 IU/day for 3 months, K2: subjects were treated with insulin 0.5–2 IU/day + placebo for 3 months. Levels of 25(OH)D, IL-17 and HbA1c were evaluated after 3 months treatment using ELISA. After 3 months treatment, results showed that 25(OH)D level was significantly higher in K1 compared with K2 (p = 0.00), IL-17 level was significantly lower K1 compared with K2 (p= 0.022). Surprisingly, HbA1c level in K1 was not significantly different with K2 (p = 0.93). Furthermore, in vitamin D-treated group, 25(OH)D level was elevated significantly after 3 months treatment with vitamin D (p = 0.00), IL-17 level was reduced significantly after 3 months treatment with vitamin D (p= 0.001)  and HbA1c level was reduced insignificantly after 3 months treatment with vitamin D (p= 0.76). Correlation study showed that there was no correlation between 25(OH)D level with IL-17 level (p= 0.160, r= -0.284) and 25(OH)D with HbA1c (p= 0.62, r= -0.10). This study can be conclude that vitamin D3 supplementation may elevate the 25(OH)D and reduce IL-17 level but did not change HbA1c level in pediatric T1DM.

Author Biographies

  • Rahmah Yasinta Rangkuti, Brawijaya University

    Department of Child Health

    Saiful Anwar Hospital

  • Harjoedi Adji Tjahjono, Brawijaya University

    Department of Child Health

    Saiful Anwar Hospital

References

Janner M, Ballinari P, Mullis PE, Flück CE (2010) High prevalence of vitamin D deficiency in children and adolescents with type 1 diabetes. Swiss Medical Weekly 140 (3): 451–460.

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

Mitri J, Pittas AG (2014) Vitamin D and diabetes. Endocrinology and Metabolism Clinics of North America 43 (1): 205–232. doi: 10.2337/diaspect.24.2.113.

Alemzadeh R, Wyatt DT. Diabetes mellitus in children. In: Kliegman R, Stanton B, St. Geme J, Schor N, eds. (2007) Nelson textbook of Pediatrics. Philadelphia, Elsevier Saunders.

Savova R (2009) Definition, epidemiology and classification of diabetes mellitus in childhood after ‘Ispad Clinical Practice Consensus Guidelines 2009 Compendium’. Pediatriya 49: 8–13.

Holt R, Hanley N (2012) Clinical diabetes and obesity. In: Essential Endocrinology and Diabetes, Holt, R & Hanley, N (eds). Oxford, Wiley-Blackwell.

Baeke F, Korf H, Overbergh L et al. (2010) Human T lymphocytes are direct targets of 1,25-dihydroxyvitamin D3 in the immune system. The Journal of Steroid Biochemistry and Molecular Biology 121 (1–2): 221–227. doi:10.1016/j.jsbmb.2010.03.037.

Takiishi T, Gysemans C, Bouillon R, Mathieu C (2010) Vitamin D and diabetes. Endocrinology Metabolism Clinics of North America 39 (2): 419–446.

Dejkhamron P, Menon RK, Sperling M (2007) Childhood diabetes mellitus: Recent advances and future prospects. Indian Journal of Medical Research 125(3): 231–250.

Gysemans C, Van-Etten E, Overbergh L, Giulietti A, Eelen G, Waer M (2008) Unaltered diabetes presentation in NOD mice lacking the vitamin D receptor. Diabetes. 57(1): 269–75.

Hyppönen E, Läärä E, Reunanen A, Järvelin MR, Virtanen SM (2001) Intake of vitamin D and risk of type 1 diabetes: A birth-cohort study. Lancet. 358(9292): 1500–1503.

Prietl B, Pilz S, Wolf M, Tomaschitz A, Obermayer-Pietsch B, Graninger W (2010) Vitamin D supplementation and regulatory T cells in apparently healthy subjects: vitamin D treatment for autoimmune diseases?. Isr Med Assoc J. 12(3): 136–139.

Dong JY, Zhang WG, Chen JJ, Zhang ZL, Han SF, Qin L-Q (2013) Vitamin D intake and risk of type 1 diabetes: a meta-analysis of observational studies. Nutrients. 5(9): 3551–3562.

Hawa MI, Valorani MG, Buckley LR, Beales PE, Afeltra A, Cacciapaglia F (2004) Lack of effect of vitamin D administration during pregnancy and early life on diabetes incidence in the non-obese diabetic mouse. Horm Metab Res. 36(9): 620–624.

Mathieu C, Decallonne B, van Etten E (2002) 1,25-dihydroxyvitamin D3: the endocrine system meets the immune system. Verh K Acad Geneeskd Belg. 64 (1): 71–82.

Svoren BM, Volkening LK, Wood JR, Laffel LMB (2009) Significant vitamin D deficiency in youth with type 1 diabetes mellitus. Journal of Pediatrics 154 (1): 132–134.

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.

Honkanen J, Nieminen JK, Gao R et al. (2010) IL-17 immunity in human type 1 diabetes. The Journal of Immunology 185 (3): 1959–1967.

Marwaha AK, Crome SQ, Panagiotopoulos C et al. (2010) Cutting edge: Increased IL-17-secreting T cells in children with new-onset type 1 diabetes. The Journal of Immunology 185 (7): 3814-3818.

Arif S, Moore F, Marks K et al. (2011) Peripheral and islet interleukin-17 pathway activation characterizes human autoimmune diabetes and promotes cytokine-mediated β-Cell Death. Diabetes 60 (8): 2112-2119.

Grieco FA, Moore F, Vigneron F et al. (2014) IL-17A increases the expression of proinflammatory chemokines in human pancreatic islets. Diabetologia 57 (3): 502–511.

Bizzari C, Pitocco D, Napoli N (2010) No protective effect of calcitriol on beta-cell function in recent-onset type 1 diabetes: The IMDIAB XIII trial. Diabetes Care 33 (9): 1962–1963.

Aljabri K, Bokhari S, Khan M (2010) Glycemic changes after vitamin D supplementation in patients with type 1 diabetes mellitus and vitamin D deficiency. Annals of Saudi Medicine 30 (6): 454–458.

Jeffery LE, Burke F, Mura M et al. (2009) 1,25-Dihydroxyvitamin D3 and IL-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.

Ferraro A, Socci C, Stabilini A et al. (2011) Expansion of Th17 cells and functional defects in T regulatory cells are key features of the pancreatic lymph nodes in patients with type 1 diabetes. Diabetes 60 (11): 2903–2913.

Nwosu BU, Maranda L (2014) The effects of vitamin D supplementation on hepatic dysfunction, vitamin D status, and glycemic control in children and adolescents with vitamin D deficiency and either type 1 or type 2 diabetes mellitus. PLoS One 9 (6): e99646. doi:10.1371/journal.pone.0099646.

Branco S, Rego H, Costa C et al. (2012) Vitamin D deficiency in children and adolescents with type 1 diabetes. Pediatric Diabetes 13: 91–92.

Tunc O, Cetinkaya S, Kizilgun M, Aycan Z (2011) Vitamin D status and insulin requirements in children and adolescent with type 1 diabetes. Journal of Pediatric Endocrinology and Metabolism 24: 10377–11041.

Magee L, Mughal Z, Ehtisham S et al. (2012) The relationship between Vitamin D and HbA1C in a type 1 diabetic paediatric population. Endocrine Abstracts 28: 38–42.

Zella JB, DeLuca HF (2003) Vitamin D and autoimmune diabetes. Journal of Cellular Biochemistry 88 (2): 216–222.

Giulietti A, Gysemans C, Stoffels K et al. (2004) Vitamin D deficiency in early life accelerates Type 1 diabetes in non-obese diabetic mice. Diabetologia 47 (3): 451–462.

Baeke Fb, Takiishi T, Korf H et al. (2010) Vitamin D: Modulator of the immune system. Current Opinion in Pharmacology 10 (4): 482–496.

Zella JB, McCary LC, DeLuca HF (2003) Oral administration of 1,25-dihydroxyvitamin D3 completely protects NOD mice from insulin-dependent diabetes mellitus. Archives of Biochemistry and Biophysics 417 (1): 77–80.

van Etten E, Mathieu C (2005) Immunoregulation by 1,25-dihydroxyvitamin D3: Basic concepts. The Journal of Steroid Biochemistry and Molecular Biology 97 (1-2): 93–101.

Downloads

Published

2017-04-18

Issue

Section

Articles