Hospital admissions for vitamin D related conditions and subsequent immune-mediated disease: record-linkage studies

PMCID: PMC3729414The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1741-7015/11/171. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Exposure to dioxin and nonneoplastic mortality in the expanded IARC international cohort study of phenoxy herbicide and chlorophenol production workers and sprayers.

The authors studied noncancer mortality among phenoxyacid herbicide and chlorophenol production workers and sprayers included in an international study comprising 36 cohorts from 12 countries followed from 1939 to 1992. Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin or higher chlorinated dioxins (TCDD/HCD) was discerned from job records and company questionnaires with validation by biologic and environmental measures. Standard mortality ratio analyses suggested a moderate healthy worker effect for all circulatory diseases, especially ischemic heart disease, among both those exposed and those not exposed to TCDD/HCD. In Poisson regression analyses, exposure to TCDD/HCD was not associated with increased mortality from cerebrovascular disease. However, an increased risk for circulatory disease, especially ischemic heart disease (rate ratio [RR] 1.67, 95% confidence interval [Cl] 1.23-2.26) and possibly diabetes (RR 2.25, 95% Cl 0.53-9.50), was present among TCDD/HCD-exposed workers. Risks tended to be higher 10 to 19 years after first exposure and for those exposed for a duration of 10 to 19 years. Mortality from suicide was comparable to that for the general population for all workers exposed to herbicides or chlorophenols and was associated with short latency and duration of exposure. More refined investigations of the ischemic heart disease and TCDD/HCD exposure association are warranted

Influence of genetic factors on toluene diisocyanate-related symptoms: evidence from a cross-sectional study

Background: Toluene diisocyanate (TDI) is a highly reactive compound used in the production of, e. g., polyurethane foams and paints. TDI is known to cause respiratory symptoms and diseases. Because TDI causes symptoms in only a fraction of exposed workers, genetic factors may play a key role in disease susceptibility. Methods: Workers (N = 132) exposed to TDI and a non-exposed group ( N = 114) were analyzed for genotype (metabolising genes: CYP1A1*2A, CYP1A1*2B, GSTM1*O, GSTM3*B, GSTP1 1105V, GSTP1 A114V, GSTT1*O, MPO -463, NAT1*3, *4, *10, *11, *14, *15, NAT2*5, *6, *7, SULT1A1 R213H; immune-related genes: CCL5 -403, HLA-DQB1* 05, TNF-308, TNF-863) and symptoms of the eyes, upper and lower airways ( based on structured interviews). Results: For three polymorphisms: CYP1A1*2A, CYP1A1*2B, and TNF -308 there was a pattern consistent with interaction between genotype and TDI exposure status for the majority of symptoms investigated, although it did reach statistical significance only for some symptoms: among TDI-exposed workers, the CYP1A1 variant carriers had increased risk (CYP1A1*2A and eye symptoms: variant carriers OR 2.0 95% CI 0.68-6.1, p-value for interaction 0.048; CYP1A1*2B and wheeze: IV carriers OR = 12, 1.4-110, p-value for interaction 0.057). TDI-exposed individuals with TNF-308 A were protected against the majority of symptoms, but it did not reach statistical significance. In the non-exposed group, however, TNF -308 A carriers showed higher risk of the majority of symptoms ( eye symptoms: variant carriers OR = 2.8, 1.1-7.1, p-value for interaction 0.12; dry cough OR = 2.2, 0.69-7.2, p-value for interaction 0.036). Individuals with SULT1A1 213H had reduced risk both in the exposed and non-exposed groups. Other polymorphisms, showed associations to certain symptoms: among TDI-exposed, NAT1*10 carriers had a higher risk of eye symptoms and CCL5 -403 AG+AA as well as HLA-DQB1 *05 carriers displayed increased risk of symptoms of the lower airways. GSTM1, GSTM3 and GSTP1 only displayed effects on symptoms of the lower airways in the non-exposed group. Conclusion: Specific gene-TDI interactions for symptoms of the eyes and lower airways appear to exist. The results suggest different mechanisms for TDI- and non- TDI-related symptoms of the eyes and lower airways

Islet antibodies and remaining beta-cell function 8 years after diagnosis of diabetes in young adults: a prospective follow-up of the nationwide Diabetes Incidence Study in Sweden.

Objectives. To establish the prevalence of remaining beta-cell function 8 years after diagnosis of diabetes in young adults and relate the findings to islet antibodies at diagnosis and 8 years later. Design. Population-based cohort study. Setting. Nationwide from all Departments of Medicine and Endocrinology in Sweden. Subjects. A total of 312 young (15-34 years old) adults diagnosed with diabetes during 1987-88. Main outcome measure. Plasma connecting peptide (C-peptide) 8 years after diagnosis. Preserved beta-cell function was defined as measurable C-peptide levels. Three islet antibodies - cytoplasmic islet cell antibodies (ICA), glutamic acid decarboxylase antibodies and tyrosine phosphatase antibodies - were measured. Results. Amongst 269 islet antibody positives (ab+) at diagnosis, preserved beta-cell function was found in 16% (42/269) 8 years later and these patients had a higher body mass index (median 22.7 and 20.5 kg m-2, respectively; P = 0.0003), an increased frequency of one islet antibody (50 and 24%, respectively; P = 0.001), and a lower prevalence of ICA (55 and 6%, respectively; P = 0.007) at diagnosis compared with ab+ without remaining beta-cell function. Amongst the 241 patients without detectable beta-cell function at follow-up, 14 lacked islet antibodies, both at diagnosis and at follow-up. Conclusions. Sixteen per cent of patients with autoimmune type 1 diabetes had remaining beta-cell function 8 years after diagnosis whereas 5.8% with beta-cell failure lacked islet autoimmunity, both at diagnosis and at follow-up

Inherited Variation in Vitamin D Genes Is Associated With Predisposition to Autoimmune Disease Type 1 Diabetes

Objective: Vitamin D deficiency (25-hydroxyvitamin D [25(OH)D] <50 nmol/L) is commonly reported in both children and adults worldwide, and growing evidence indicates that vitamin D deficiency is associated with many extraskeletal chronic disorders, including the autoimmune diseases type 1 diabetes and multiple sclerosis. Research Design and Methods: We measured 25(OH)D concentrations in 720 case and 2,610 control plasma samples and genotyped single nucleotide polymorphisms from seven vitamin D metabolism genes in 8,517 case, 10,438 control, and 1,933 family samples. We tested genetic variants influencing 25(OH)D metabolism for an association with both circulating 25(OH)D concentrations and disease status. Results: Type 1 diabetic patients have lower circulating levels of 25(OH)D than similarly aged subjects from the British population. Only 4.3 and 18.6% of type 1 diabetic patients reached optimal levels ($\geq$75 nmol/L) of 25(OH)D for bone health in the winter and summer, respectively. We replicated the associations of four vitamin D metabolism genes (GC, DHCR7, CYP2R1, and CYP24A1) with 25(OH)D in control subjects. In addition to the previously reported association between type 1 diabetes and CYP27B1 (P = 1.4 × 10$^{−4}$), we obtained consistent evidence of type 1 diabetes being associated with DHCR7 (P = 1.2 × 10$^{−3}$) and CYP2R1 (P = 3.0 × 10$^{−3}$). Conclusions: Circulating levels of 25(OH)D in children and adolescents with type 1 diabetes vary seasonally and are under the same genetic control as in the general population but are much lower. Three key 25(OH)D metabolism genes show consistent evidence of association with type 1 diabetes risk, indicating a genetic etiological role for vitamin D deficiency in type 1 diabetes

HLA Genes, Islet Autoantibodies and Residual C-Peptide at the Clinical Onset of Type 1 Diabetes Mellitus and the Risk of Retinopathy 15 Years Later

HLA genes, islet autoantibodies and residual C-peptide were studied to determine the independent association of each exposure with diabetic retinopathy (DR), 15 years after the clinical onset of type 1 diabetes in 15-34 year old individuals.The cohort was identified in 1992 and 1993 by the Diabetes Incidence Study in Sweden (DISS), which investigates incident cases of diabetes for patients between 15 and 34 years of age. Blood samples at diagnosis were analyzed to determine HLA genotype, islet autoantibodies and serum C-peptide. In 2009, fundus photographs were obtained from patient records. Study measures were supplemented with data from the Swedish National Diabetes Registry.The prevalence of DR was 60.2% (148/246). Autoantibodies against the 65 kD isoform of glutamate decarboxylase (GADA) at the onset of clinical diabetes increased the risk of DR 15 years later, relative risk 1.12 for each 100 WHO units/ml, [95% CI 1.02 to 1.23]. This equates to risk estimates of 1.27, [95% CI 1.04 to 1.62] and 1.43, [95% CI 1.06 to 1.94] for participants in the highest 25(th) (GADA>233 WHO units/ml) and 5(th) percentile (GADA>319 WHO units/ml) of GADA, respectively. These were adjusted for duration of diabetes, HbA(1c), treated hypertension, sex, age at diagnosis, HLA and C-peptide. Islet cell autoantibodies, insulinoma-antigen 2 autoantibodies, residual C-peptide and the type 1 diabetes associated haplotypes DQ2, DQ8 and DQ6 were not associated with DR.Increased levels of GADA at the onset of type 1 diabetes were associated with DR 15 years later. These results, if confirmed, could provide additional insights into the pathogenesis of the most common microvascular complication of diabetes and lead to better risk stratification for both patient screenings and DR treatment trials