Diabetologia

, Volume 57, Issue 5, pp 902–908 | Cite as

Prevalence of vitamin D deficiency in pre-type 1 diabetes and its association with disease progression

  • Jennifer Raab
  • Eleni Z. Giannopoulou
  • Simone Schneider
  • Katharina Warncke
  • Miriam Krasmann
  • Christiane Winkler
  • Anette-Gabriele Ziegler
Article

Abstract

Aims/hypothesis

Vitamin D deficiency is common in people with type 1 diabetes, but its role in disease progression is unclear. Our aim was to assess the prevalence of vitamin D deficiency in prediabetes (defined as the presence of multiple islet autoantibodies), and investigate whether or not progression to type 1 diabetes is faster in children with vitamin D deficiency and multiple islet autoantibodies.

Methods

Levels of 25-hydroxyvitamin D [25(OH)D] were measured in 108 children with multiple islet autoantibodies within 2 years of islet autoantibody seroconversion, in 406 children who remained islet autoantibody-negative and in 244 patients with newly diagnosed type 1 diabetes. Children with multiple islet autoantibodies were prospectively followed for a median of 5.8 years (interquartile range 3.4–8.6 years) to monitor progression to type 1 diabetes.

Results

In the cross-sectional analysis, 25(OH)D levels were lower and the prevalence of vitamin D deficiency (<50 nmol/l) was higher in children with prevalent multiple islet autoantibodies than in islet autoantibody-negative children (59.9 ± 3.0 vs 71.9 ± 1.5 nmol/l; p < 0.001; 39.8% vs 28.3%; p = 0.021). The differences in vitamin D levels between the groups were greatest in summer. The cumulative incidence of type 1 diabetes at 10 years after seroconversion was similar between children with vitamin D deficiency and those with sufficient vitamin D levels (51.8% [95% CI 29.3, 74.3] vs 55.4% [95% CI 35.5, 72.3], p = 0.8).

Conclusions/interpretation

Vitamin D levels were lower in children with multiple islet autoantibodies and in children with type 1 diabetes than in autoantibody-negative children. However, vitamin D deficiency was not associated with faster progression to type 1 diabetes in children with multiple islet autoantibodies.

Keywords

25(OH)D Islet autoimmunity Type 1 diabetes Vitamin D 

Abbreviations

25(OH)D

25-Hydroxyvitamin D

IQR

Interquartile range

Supplementary material

125_2014_3181_MOESM1_ESM.pdf (21 kb)
ESM Table 1(PDF 20 kb)

References

  1. 1.
    Eisenbarth GS (1986) Type I diabetes mellitus. A chronic autoimmune disease. N Engl J Med 314:1360–1368PubMedCrossRefGoogle Scholar
  2. 2.
    Ziegler AG, Rewers M, Simell O et al (2013) Seroconversion to multiple islet autoantibodies and risk of progression to diabetes in children. JAMA 309:2473–2479PubMedCrossRefGoogle Scholar
  3. 3.
    Atkinson MA, Eisenbarth GS (2001) Type 1 diabetes: new perspectives on disease pathogenesis and treatment. Lancet 358:221–229PubMedCrossRefGoogle Scholar
  4. 4.
    Luong K, Nguyen LT, Nguyen DN (2005) The role of vitamin D in protecting type 1 diabetes mellitus. Diabetes Metab Res Rev 21:338–346PubMedCrossRefGoogle Scholar
  5. 5.
    Chakhtoura M, Azar ST (2013) The role of vitamin D deficiency in the incidence, progression, and complications of type 1 diabetes mellitus. Int J Endocrinol 2013:148673Google Scholar
  6. 6.
    Baumgartl HJ, Standl E, Schmidt-Gayk H, Kolb HJ, Janka HU, Ziegler AG (1991) Changes of vitamin D3 serum concentrations at the onset of immune-mediated type 1 (insulin-dependent) diabetes mellitus. Diabetes Res 16:145–148PubMedGoogle Scholar
  7. 7.
    Pozzilli P, Manfrini S, Crino A et al (2005) Low levels of 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 in patients with newly diagnosed type 1 diabetes. Horm Metab Res 37:680–683PubMedCrossRefGoogle Scholar
  8. 8.
    Littorin B, Blom P, Scholin A et al (2006) Lower levels of plasma 25-hydroxyvitamin D among young adults at diagnosis of autoimmune type 1 diabetes compared with control subjects: results from the nationwide Diabetes Incidence Study in Sweden (DISS). Diabetologia 49:2847–2852PubMedCrossRefGoogle Scholar
  9. 9.
    Bierschenk L, Alexander J, Wasserfall C, Haller M, Schatz D, Atkinson M (2009) Vitamin D levels in subjects with and without type 1 diabetes residing in a solar rich environment. Diabetes Care 32:1977–1979PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Ziegler AG, Baumgartl HJ, Ede G et al (1990) Low-pigment skin type and predisposition for development of type I diabetes. Diabetes Care 13:529–531PubMedCrossRefGoogle Scholar
  11. 11.
    Baeke F, Takiishi T, Korf H, Gysemans C, Mathieu C (2010) Vitamin D: modulator of the immune system. Curr Opin Pharmacol 10:482–496PubMedCrossRefGoogle Scholar
  12. 12.
    Badenhoop K, Kahles H, Penna-Martinez M (2012) Vitamin D, immune tolerance, and prevention of type 1 diabetes. Curr Diab Rep 12:635–642PubMedCrossRefGoogle Scholar
  13. 13.
    Fassbender WJ, Goertz B, Weismuller K et al (2002) VDR gene polymorphisms are overrepresented in German patients with type 1 diabetes compared to healthy controls without effect on biochemical parameters of bone metabolism. Horm Metab Res 34:330–337PubMedCrossRefGoogle Scholar
  14. 14.
    Frederiksen B, Liu E, Romanos J et al (2013) Investigation of the vitamin D receptor gene (VDR) and its interaction with protein tyrosine phosphatase, non-receptor type 2 gene (PTPN2) on risk of islet autoimmunity and type 1 diabetes: the Diabetes Autoimmunity Study in the Young (DAISY). J Steroid Biochem Mol Biol 133:51–57PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Gorham ED, Garland CF, Burgi AA et al (2012) Lower prediagnostic serum 25-hydroxyvitamin D concentration is associated with higher risk of insulin-requiring diabetes: a nested case-control study. Diabetologia 55:3224–3227PubMedCrossRefGoogle Scholar
  16. 16.
    Munger KL, Levin LI, Massa J, Horst R, Orban T, Ascherio A (2013) Preclinical serum 25-hydroxyvitamin D levels and risk of type 1 diabetes in a cohort of US military personnel. Am J Epidemiol 177:411–419PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Hyppönen E, Läärä E, Reunanen A, Järvelin M-R, Virtanen SM (2001) Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study. Lancet 358:1500–1503PubMedCrossRefGoogle Scholar
  18. 18.
    Simpson M, Brady H, Yin X et al (2011) No association of vitamin D intake or 25-hydroxyvitamin D levels in childhood with risk of islet autoimmunity and type 1 diabetes: the Diabetes Autoimmunity Study in the Young (DAISY). Diabetologia 54:2779–2788PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Skyler JS (2013) Primary and secondary prevention of type 1 diabetes. Diabet Med 30:161–169PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Ziegler AG, Hummel M, Schenker M, Bonifacio E (1999) Autoantibody appearance and risk for development of childhood diabetes in offspring of parents with type 1 diabetes: the 2-year analysis of the German BABYDIAB Study. Diabetes 48:460–468PubMedCrossRefGoogle Scholar
  21. 21.
    Ziegler AG, Meier-Stiegen F, Winkler C, Bonifacio E (2012) Prospective evaluation of risk factors for the development of islet autoimmunity and type 1 diabetes during puberty—TEENDIAB: study design. Pediatr Diabetes 13:438–443CrossRefGoogle Scholar
  22. 22.
    Hummel S, Pflüger M, Hummel M, Bonifacio E, Ziegler AG (2011) Primary dietary intervention study to reduce the risk of islet autoimmunity in children at increased risk for type 1 diabetes: the BABYDIET study. Diabetes Care 34:1301–1305PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Thümer L, Adler K, Bonifacio E et al (2010) German new onset diabetes in the young incident cohort study: DiMelli study design and first-year results. Rev Diabet Stud 7:202–208PubMedCentralPubMedGoogle Scholar
  24. 24.
    Puavilai G, Chanprasertyotin S, Sriphrapradaeng A (1999) Diagnostic criteria for diabetes mellitus and other categories of glucose intolerance: 1997 criteria by the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus (ADA), 1998 WHO consultation criteria, and 1985 WHO criteria. World Health Organization. Diabetes Res Clin Pract 44:21–26PubMedCrossRefGoogle Scholar
  25. 25.
    Achenbach P, Lampasona V, Landherr U et al (2009) Autoantibodies to zinc transporter 8 and SLC30A8 genotype stratify type 1 diabetes risk. Diabetologia 52:1881–1888PubMedCrossRefGoogle Scholar
  26. 26.
    Törn C, Mueller PW, Schlosser M, Bonifacio E, Bingley PJ (2008) Diabetes Antibody Standardization Program: evaluation of assays for autoantibodies to glutamic acid decarboxylase and islet antigen-2. Diabetologia 51:846–852PubMedCrossRefGoogle Scholar
  27. 27.
    Schlosser M, Mueller PW, Torn C, Bonifacio E, Bingley PJ (2010) Diabetes Antibody Standardization Program: evaluation of assays for insulin autoantibodies. Diabetologia 53:2611–2620PubMedCrossRefGoogle Scholar
  28. 28.
    Lampasona V, Schlosser M, Mueller PW et al (2011) Diabetes antibody standardization program: first proficiency evaluation of assays for autoantibodies to zinc transporter 8. Clin Chem 57:1693–1702PubMedCrossRefGoogle Scholar
  29. 29.
    Kumar J, Muntner P, Kaskel FJ, Hailpern SM, Melamed ML (2009) Prevalence and associations of 25-hydroxyvitamin D deficiency in US children: NHANES 2001-2004. Pediatrics 124:e362–e370PubMedCentralPubMedCrossRefGoogle Scholar
  30. 30.
    Frederiksen BN, Kroehl M, Fingerlin TE et al (2013) Association between vitamin D metabolism gene polymorphisms and risk of islet autoimmunity and progression to type 1 diabetes: the Diabetes Autoimmunity Study in the Young (DAISY). J Clin Endocrinol Metab 98:E1845–1851SPubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Jennifer Raab
    • 1
    • 2
  • Eleni Z. Giannopoulou
    • 1
    • 2
  • Simone Schneider
    • 1
  • Katharina Warncke
    • 1
    • 2
    • 3
  • Miriam Krasmann
    • 2
  • Christiane Winkler
    • 1
    • 2
  • Anette-Gabriele Ziegler
    • 1
    • 2
  1. 1.Forschergruppe Diabetes e.V.NeuherbergGermany
  2. 2.Institute of Diabetes Research, Helmholtz Zentrum München, and Forschergruppe Diabetes, Klinikum rechts der IsarTechnische Universität MünchenNeuherbergGermany
  3. 3.Department of Pediatrics, Klinikum rechts der IsarTechnische Universität MünchenMunichGermany

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