Skip to main content
Top
Published in: Diabetologia 5/2014

01-05-2014 | Article

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

Authors: Jennifer Raab, Eleni Z. Giannopoulou, Simone Schneider, Katharina Warncke, Miriam Krasmann, Christiane Winkler, Anette-Gabriele Ziegler

Published in: Diabetologia | Issue 5/2014

Login to get access

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.
Appendix
Available only for authorised users
Literature
1.
go back to reference Eisenbarth GS (1986) Type I diabetes mellitus. A chronic autoimmune disease. N Engl J Med 314:1360–1368PubMedCrossRef Eisenbarth GS (1986) Type I diabetes mellitus. A chronic autoimmune disease. N Engl J Med 314:1360–1368PubMedCrossRef
2.
go back to reference Ziegler AG, Rewers M, Simell O et al (2013) Seroconversion to multiple islet autoantibodies and risk of progression to diabetes in children. JAMA 309:2473–2479PubMedCrossRef Ziegler AG, Rewers M, Simell O et al (2013) Seroconversion to multiple islet autoantibodies and risk of progression to diabetes in children. JAMA 309:2473–2479PubMedCrossRef
3.
go back to reference Atkinson MA, Eisenbarth GS (2001) Type 1 diabetes: new perspectives on disease pathogenesis and treatment. Lancet 358:221–229PubMedCrossRef Atkinson MA, Eisenbarth GS (2001) Type 1 diabetes: new perspectives on disease pathogenesis and treatment. Lancet 358:221–229PubMedCrossRef
4.
go back to reference Luong K, Nguyen LT, Nguyen DN (2005) The role of vitamin D in protecting type 1 diabetes mellitus. Diabetes Metab Res Rev 21:338–346PubMedCrossRef Luong K, Nguyen LT, Nguyen DN (2005) The role of vitamin D in protecting type 1 diabetes mellitus. Diabetes Metab Res Rev 21:338–346PubMedCrossRef
5.
go back to reference 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 2013:148673 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 2013:148673
6.
go back to reference 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 16:145–148PubMed 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 16:145–148PubMed
7.
go back to reference 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 37:680–683PubMedCrossRef 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 37:680–683PubMedCrossRef
8.
go back to reference 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 49:2847–2852PubMedCrossRef 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 49:2847–2852PubMedCrossRef
9.
go back to reference 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 32:1977–1979PubMedCentralPubMedCrossRef 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 32:1977–1979PubMedCentralPubMedCrossRef
10.
go back to reference Ziegler AG, Baumgartl HJ, Ede G et al (1990) Low-pigment skin type and predisposition for development of type I diabetes. Diabetes Care 13:529–531PubMedCrossRef Ziegler AG, Baumgartl HJ, Ede G et al (1990) Low-pigment skin type and predisposition for development of type I diabetes. Diabetes Care 13:529–531PubMedCrossRef
11.
go back to reference Baeke F, Takiishi T, Korf H, Gysemans C, Mathieu C (2010) Vitamin D: modulator of the immune system. Curr Opin Pharmacol 10:482–496PubMedCrossRef Baeke F, Takiishi T, Korf H, Gysemans C, Mathieu C (2010) Vitamin D: modulator of the immune system. Curr Opin Pharmacol 10:482–496PubMedCrossRef
12.
go back to reference Badenhoop K, Kahles H, Penna-Martinez M (2012) Vitamin D, immune tolerance, and prevention of type 1 diabetes. Curr Diab Rep 12:635–642PubMedCrossRef Badenhoop K, Kahles H, Penna-Martinez M (2012) Vitamin D, immune tolerance, and prevention of type 1 diabetes. Curr Diab Rep 12:635–642PubMedCrossRef
13.
go back to reference 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 34:330–337PubMedCrossRef 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 34:330–337PubMedCrossRef
14.
go back to reference 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 133:51–57PubMedCentralPubMedCrossRef 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 133:51–57PubMedCentralPubMedCrossRef
15.
go back to reference 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 55:3224–3227PubMedCrossRef 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 55:3224–3227PubMedCrossRef
16.
go back to reference 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 177:411–419PubMedCentralPubMedCrossRef 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 177:411–419PubMedCentralPubMedCrossRef
17.
go back to reference 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 358:1500–1503PubMedCrossRef 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 358:1500–1503PubMedCrossRef
18.
go back to reference 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 54:2779–2788PubMedCentralPubMedCrossRef 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 54:2779–2788PubMedCentralPubMedCrossRef
20.
go back to reference 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 48:460–468PubMedCrossRef 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 48:460–468PubMedCrossRef
21.
go back to reference 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 13:438–443CrossRef 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 13:438–443CrossRef
22.
go back to reference 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 34:1301–1305PubMedCentralPubMedCrossRef 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 34:1301–1305PubMedCentralPubMedCrossRef
23.
go back to reference 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 7:202–208PubMedCentralPubMed 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 7:202–208PubMedCentralPubMed
24.
go back to reference 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 44:21–26PubMedCrossRef 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 44:21–26PubMedCrossRef
25.
go back to reference Achenbach P, Lampasona V, Landherr U et al (2009) Autoantibodies to zinc transporter 8 and SLC30A8 genotype stratify type 1 diabetes risk. Diabetologia 52:1881–1888PubMedCrossRef Achenbach P, Lampasona V, Landherr U et al (2009) Autoantibodies to zinc transporter 8 and SLC30A8 genotype stratify type 1 diabetes risk. Diabetologia 52:1881–1888PubMedCrossRef
26.
go back to reference 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 51:846–852PubMedCrossRef 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 51:846–852PubMedCrossRef
27.
go back to reference Schlosser M, Mueller PW, Torn C, Bonifacio E, Bingley PJ (2010) Diabetes Antibody Standardization Program: evaluation of assays for insulin autoantibodies. Diabetologia 53:2611–2620PubMedCrossRef Schlosser M, Mueller PW, Torn C, Bonifacio E, Bingley PJ (2010) Diabetes Antibody Standardization Program: evaluation of assays for insulin autoantibodies. Diabetologia 53:2611–2620PubMedCrossRef
28.
go back to reference 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 57:1693–1702PubMedCrossRef 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 57:1693–1702PubMedCrossRef
29.
go back to reference 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–e370PubMedCentralPubMedCrossRef 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–e370PubMedCentralPubMedCrossRef
30.
go back to reference 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:E1845–1851SPubMedCrossRef 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:E1845–1851SPubMedCrossRef
Metadata
Title
Prevalence of vitamin D deficiency in pre-type 1 diabetes and its association with disease progression
Authors
Jennifer Raab
Eleni Z. Giannopoulou
Simone Schneider
Katharina Warncke
Miriam Krasmann
Christiane Winkler
Anette-Gabriele Ziegler
Publication date
01-05-2014
Publisher
Springer Berlin Heidelberg
Published in
Diabetologia / Issue 5/2014
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-014-3181-4

Other articles of this Issue 5/2014

Diabetologia 5/2014 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.