Reduced serum vitamin D-binding protein levels are associated with type 1 diabetes

Dustin Blanton, Zhao Han, Lindsey Bierschenk, M. V.Prasad Linga-Reddy, Hongjie Wang, Michael Clare-Salzler, Michael Haller, Desmond Schatz, Courtney Myhr, Jin-Xiong She, Clive Wasserfall, Mark Atkinson

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Abstract

OBJECTIVE - Previous studies have noted a specific association between type 1 diabetes and insufficient levels of vitamin D, as well as polymorphisms within genes related to vitamin D pathways. Here, we examined whether serum levels or genotypes of the vitamin D-binding protein (VDBP), a molecule key to the biologic actions of vitamin D, specifically associate with the disorder. RESEARCH DESIGN AND METHODS - A retrospective, cross-sectional analysis of VDBP levels used samples from 472 individuals of similar age and sex distribution, including 153 control subjects, 203 patients with type 1 diabetes, and 116 first-degree relatives of type 1 diabetic patients. Single nucleotide polymorphism (SNP) typing for VDBP polymorphisms (SNP rs4588 and rs7041) was performed on this cohort to determine potential genetic correlations. In addition, SNP analysis of a second sample set of banked DNA samples from 1,502 type 1 diabetic patients and 1,880 control subjects also was used to determine genotype frequencies. RESULTS - Serum VDBP levels were highest in healthy control subjects (median 423.5 μg/mL [range 193.5-4,345.0; interquartile range 354.1-586]), intermediate in first-degree relatives (402.9 μg/mL [204.7-4,850.0; 329.6-492.4]), and lowest in type 1 diabetic patients (385.3 μg/mL [99.3-1,305.0; 328.3-473.0]; P = 0.003 vs. control subjects). VDBP levels did not associate with serum vitamin D levels, age, or disease duration. However, VDBP levels were, overall, lower in male subjects (374.7 μg/mL [188.9-1,602.0; 326.9-449.9]) than female subjects (433.4 μg/mL [99.3-4,850.0; 359.4-567.8]; P < 0.0001). It is noteworthy that no differences in genotype frequencies of the VDBP polymorphisms were associated with serum VDBP levels or between type 1 diabetic patients and control subjects. CONCLUSIONS - Serum VDBP levels are decreased in those with type 1 diabetes. These studies suggest that multiple components in the metabolic pathway of vitamin D may be altered in type 1 diabetes and, collectively, have the potential to influence disease pathogenesis.

Original languageEnglish (US)
Pages (from-to)2566-2570
Number of pages5
JournalDiabetes
Volume60
Issue number10
DOIs
StatePublished - Oct 1 2011

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Vitamin D-Binding Protein
Type 1 Diabetes Mellitus
Blood Proteins
Vitamin D
Single Nucleotide Polymorphism
Genotype
Sex Distribution
Age Distribution
Metabolic Networks and Pathways
Serum
Healthy Volunteers
Research Design
Cross-Sectional Studies

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Blanton, D., Han, Z., Bierschenk, L., Linga-Reddy, M. V. P., Wang, H., Clare-Salzler, M., ... Atkinson, M. (2011). Reduced serum vitamin D-binding protein levels are associated with type 1 diabetes. Diabetes, 60(10), 2566-2570. https://doi.org/10.2337/db11-0576

Reduced serum vitamin D-binding protein levels are associated with type 1 diabetes. / Blanton, Dustin; Han, Zhao; Bierschenk, Lindsey; Linga-Reddy, M. V.Prasad; Wang, Hongjie; Clare-Salzler, Michael; Haller, Michael; Schatz, Desmond; Myhr, Courtney; She, Jin-Xiong; Wasserfall, Clive; Atkinson, Mark.

In: Diabetes, Vol. 60, No. 10, 01.10.2011, p. 2566-2570.

Research output: Contribution to journalArticle

Blanton, D, Han, Z, Bierschenk, L, Linga-Reddy, MVP, Wang, H, Clare-Salzler, M, Haller, M, Schatz, D, Myhr, C, She, J-X, Wasserfall, C & Atkinson, M 2011, 'Reduced serum vitamin D-binding protein levels are associated with type 1 diabetes', Diabetes, vol. 60, no. 10, pp. 2566-2570. https://doi.org/10.2337/db11-0576
Blanton D, Han Z, Bierschenk L, Linga-Reddy MVP, Wang H, Clare-Salzler M et al. Reduced serum vitamin D-binding protein levels are associated with type 1 diabetes. Diabetes. 2011 Oct 1;60(10):2566-2570. https://doi.org/10.2337/db11-0576
Blanton, Dustin ; Han, Zhao ; Bierschenk, Lindsey ; Linga-Reddy, M. V.Prasad ; Wang, Hongjie ; Clare-Salzler, Michael ; Haller, Michael ; Schatz, Desmond ; Myhr, Courtney ; She, Jin-Xiong ; Wasserfall, Clive ; Atkinson, Mark. / Reduced serum vitamin D-binding protein levels are associated with type 1 diabetes. In: Diabetes. 2011 ; Vol. 60, No. 10. pp. 2566-2570.
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AU - Wang, Hongjie

AU - Clare-Salzler, Michael

AU - Haller, Michael

AU - Schatz, Desmond

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N2 - OBJECTIVE - Previous studies have noted a specific association between type 1 diabetes and insufficient levels of vitamin D, as well as polymorphisms within genes related to vitamin D pathways. Here, we examined whether serum levels or genotypes of the vitamin D-binding protein (VDBP), a molecule key to the biologic actions of vitamin D, specifically associate with the disorder. RESEARCH DESIGN AND METHODS - A retrospective, cross-sectional analysis of VDBP levels used samples from 472 individuals of similar age and sex distribution, including 153 control subjects, 203 patients with type 1 diabetes, and 116 first-degree relatives of type 1 diabetic patients. Single nucleotide polymorphism (SNP) typing for VDBP polymorphisms (SNP rs4588 and rs7041) was performed on this cohort to determine potential genetic correlations. In addition, SNP analysis of a second sample set of banked DNA samples from 1,502 type 1 diabetic patients and 1,880 control subjects also was used to determine genotype frequencies. RESULTS - Serum VDBP levels were highest in healthy control subjects (median 423.5 μg/mL [range 193.5-4,345.0; interquartile range 354.1-586]), intermediate in first-degree relatives (402.9 μg/mL [204.7-4,850.0; 329.6-492.4]), and lowest in type 1 diabetic patients (385.3 μg/mL [99.3-1,305.0; 328.3-473.0]; P = 0.003 vs. control subjects). VDBP levels did not associate with serum vitamin D levels, age, or disease duration. However, VDBP levels were, overall, lower in male subjects (374.7 μg/mL [188.9-1,602.0; 326.9-449.9]) than female subjects (433.4 μg/mL [99.3-4,850.0; 359.4-567.8]; P < 0.0001). It is noteworthy that no differences in genotype frequencies of the VDBP polymorphisms were associated with serum VDBP levels or between type 1 diabetic patients and control subjects. CONCLUSIONS - Serum VDBP levels are decreased in those with type 1 diabetes. These studies suggest that multiple components in the metabolic pathway of vitamin D may be altered in type 1 diabetes and, collectively, have the potential to influence disease pathogenesis.

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