RESUMEN
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.
Asunto(s)
Diabetes Mellitus Tipo 1/sangre , Proteína de Unión a Vitamina D/sangre , Vitamina D/análogos & derivados , Adolescente , Adulto , Estudios de Casos y Controles , Niño , Diabetes Mellitus Tipo 1/metabolismo , Femenino , Genotipo , Humanos , Masculino , Polimorfismo de Nucleótido Simple , Estudios Retrospectivos , Vitamina D/sangre , Proteína de Unión a Vitamina D/metabolismo , Adulto JovenRESUMEN
OBJECTIVE: Previous studies, largely in northern Europe, have suggested an association between type 1 diabetes and reduced serum 25-hydroxy(OH) vitamin D levels, a concept we tested in individuals residing in a solar-rich region (Florida). RESEARCH DESIGN AND METHODS: Serum samples from 415 individuals residing in Florida were cross-sectionally analyzed: 153 control subjects, 46 new-onset type 1 diabetic patients, 110 established type 1 diabetic patients (samples >or=5 months from diagnosis), and 106 first-degree relatives of the diabetic patients. RESULTS: In this study, 25-OH vitamin D levels (median, range, interquartile range [IQR]) were similar among control subjects (20.1, below detection [bd]-163.5, 13.0-37.4 ng/ml), new-onset type 1 diabetic patients (21.2, bd-48.6, 12.2-30.2 ng/ml), established type 1 diabetic patients (23.2, bd-263.8, 13.8-33.9 ng/ml), and first-degree relatives (22.2, bd-59.9, 12.7-33.1 ng/ml) (P = 0.87). Mean 25-OH vitamin D levels were less than the optimal World Health Organization level of 30 ng/ml in all study groups. CONCLUSIONS: Reduced serum 25-OH vitamin D levels were not specifically associated with type 1 diabetes. The uniform suboptimal 225-OH vitamin D levels, despite residence in a zone with abundant sunshine, support additional dietary vitamin D fortification practices.