Reduced Serum Vitamin D–Binding Protein Levels Are Associated With Type 1 Diabetes
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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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A plethora of environmental influences have been purported to affect the epidemiology of type 1 diabetes, with infant and adolescent diets, vitamin D and vitamin D pathway constituents, and viruses receiving the most focus.
“A plethora of environmental influences have been purported to affect the epidemiology of type 1 diabetes,25 with infant and adolescent diets,26 vitamin D and vitamin D pathway constituents,27–29 and viruses receiving the most focus.30,31”
From Type 1 diabetes (2014) · cites this paper as [28]
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- Authors
- Blanton, D., Han, Z., Bierschenk, L., Linga-Reddy, M. V. P., Wang, H., Clare-Salzler, M., Haller, M., Schatz, D., Myhr, C., She, J.-X., Wasserfall, C., & Atkinson, M.
- Affiliations
- University of Florida Health (US)
- Center for Biotechnology and Genomic Medicine, Georgia Health Sciences University, Augusta, Georgia
- Corresponding author
- Atkinson, Mark
- ORCID
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2011-09-16
- Volume
- 60
- Issue
- 10
- Pages
- 2566-2570
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- PMC
- PMC3178281
- OpenAlex
- W2105826013
- Cited by
- 137
- References
- 20
- Citations by year
- 2025: 5 · 2024: 5 · 2023: 7 · 2022: 9 · 2021: 8 · 2020: 11 · 2019: 14 · 2018: 12 · 2017: 9 · 2016: 9 · 2015: 12 · 2014: 11 · 2013: 13 · 2012: 10
- FWCI
- 8.10
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Diabetes (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (UL1TR000064, TL1TR000066)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Vitamin D Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- type 1 diabetes, vitamin D binding protein, rs4588, rs7041, sex differences, genetic susceptibility, vitamin D, first-degree relatives, genetic association, single nucleotide polymorphisms, susceptibility genes
- MeSH terms
- Adolescent, Adult, Child, Diabetes Mellitus, Type 1, Female, Genotype, Humans, Male, Retrospective Studies, Vitamin D, Vitamin D-Binding Protein, Case-Control Studies, Polymorphism, Single Nucleotide, Young Adult
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