Investigating iron intake in risk of progression from islet autoimmunity to type 1 diabetes: The diabetes autoimmunity study in the young.

Background: Studies of the role of iron in the risk of type 1 diabetes (T1D) have been inconsistent. Given that iron generates reactive oxygen radicals, which can lead to oxidative damage and apoptosis in the beta cells of the pancreas, we examined whether iron intake was associated with the risk of progressing to T1D in individuals with islet autoimmunity (IA), the pre-clinical phase of T1D. Methods: DAISY is a prospective cohort following 2,547 children at increased risk for IA and progression to T1D. IA is defined as at least two consecutive serum samples positive for at least one autoantibody (insulin, GAD, IA-2, or ZnT8). We measured dietary intake at the time of IA seroconversion in 175 children with IA, and of these, 64 progressed to T1D. We used Cox regression to examine the association between energy-adjusted iron intake and progression to T1D, adjusting for HLA-DR3/4 genotype, race/ethnicity, age at seroconversion, presence of multiple autoantibodies at seroconversion, and multiple vitamin use. In addition, we tested whether this association was modified by vitamin C or calcium intake. Results: In children with IA, high iron intake (as defined as above the 75th percentile, > 20.3 mg/day) was associated with decreased risk of progression to T1D compared to moderate iron intake (as defined by the middle 25-75th percentiles, 12.7-20.3 mg/day) (adjusted hazard ratio (HR): 0.35; 95% confidence interval (CI): 0.15, 0.79). The association between iron intake and T1D was not modified by vitamin C nor calcium intake. In a sensitivity analysis, the removal of six children who had been diagnosed with celiac disease prior to IA seroconversion did not affect this association. Conclusion: Higher iron intake at the time of IA seroconversion is associated with a lower risk of progression to T1D, independent of multivitamin supplement use. Further research that includes plasma biomarkers of iron status is needed to investigate the relationship between iron and the risk of T1D.

Factors associated with progression to inflammatory arthritis in first-degree relatives of individuals with RA following autoantibody positive screening in a non-clinical setting.

OBJECTIVES: Little is known about the likelihood of developing inflammatory arthritis (IA) in individuals who screen autoantibody positive (aAb+) in a non-clinical research setting. METHODS: We screened for serum cyclic citrullinated peptide antibody (anti-CCP) and rheumatoid factor isotype aAbs in subjects who were at increased risk for rheumatoid arthritis (RA) because they are a first-degree relative of an individual with classified RA (n=1780). We evaluated combinations of aAbs and high titre aAbs, as defined by 2-times (2 x) the standard cut-off and an optimal cut-off, as predictors of our two outcomes, aAb+ persistence and incident IA. RESULTS: 304 subjects (17.1%) tested aAb+; of those, 131 were IA-free and had at least one follow-up visit. Sixty-four per cent of these tested aAb+ again on their next visit. Anti-CCP+ at levels ≥2 x the standard cut-off was associated with 13-fold higher likelihood of aAb +persistence. During a median of 4.4 years (IQR: 2.2-7.2), 20 subjects (15.3%) developed IA. Among subjects that screened anti-CCP+ at ≥ 2 x or ≥an optimal cut-off, 32% and 26% had developed IA within 5 years, respectively. Both anti-CCP cut-offs conferred an approximate fourfold increased risk of future IA (HR 4.09 and HR 3.95, p<0.01). CONCLUSIONS: These findings support that aAb screening in a non-clinical setting can identify RA-related aAb+ individuals, as well as levels and combinations of aAbs that are associated with higher risk for future IA. Monitoring for the development of IA in aAb+ individuals and similar aAb testing approaches in at-risk populations may identify candidates for prevention studies in RA.

Plasma micronutrients are associated with dietary intake and environmental tobacco smoke exposure in a paediatric population.

BACKGROUND: While adult populations have been well described in terms of nutritional status, such as the concentration of nutrient biomarkers, little work has been done in healthy paediatric populations. OBJECTIVE: The primary objective of this analysis was to explore the determinants of plasma micronutrients in a group of healthy infants and children. DESIGN: The Diabetes Autoimmunity Study in the Young (DAISY) has enrolled 1433 newborns at increased risk for type 1 diabetes in Denver, Colorado. A representative random sample of 257 children from the DAISY cohort between the ages of 9 months and 8 years with a total of 815 clinic visits over time was used in this analysis. Annual dietary intake was assessed over time with Willett food-frequency questionnaires that were validated in this population. Environmental tobacco smoke (ETS) was assessed using a validated survey. Plasma samples were tested for vitamins, carotenoids and total lipids. Predictors of plasma micronutrients were evaluated using mixed models for longitudinal data, while adjusting for age, human leukocyte antigen genotype, type 1 diabetes family history and other potential confounders and covariates. RESULTS: Increased micronutrient intake was associated with increased levels of their respective plasma nutrient, with the exception of gamma-tocopherol. Independent of dietary intake, levels of alpha- and beta-carotene and beta-cryptoxanthin were significantly lower, and gamma-tocopherol was significantly higher, in children who were exposed to ETS. CONCLUSION: Dietary intake predicts plasma micronutrient levels. Exposure to ETS potentially could have negative health effects in this young population.

Validation of a five-question survey to assess a child's exposure to environmental tobacco smoke.

PURPOSE: To study the potentially adverse health effects of environmental tobacco smoke (ETS) exposure in young children, a short five-question survey was developed to identify routine exposure to ETS in a large epidemiological study. METHODS: The survey is administered to parents of a healthy cohort of children starting at age 3 months. To validate the survey, urinary cotinine levels were measured on 50 children from this cohort who were selected based on ETS exposure as reported in the survey: 24 with no exposure and 26 with exposure. Cotinine was adjusted for creatinine. RESULTS: Overall, children with some form of reported ETS exposure had urinary cotinine levels 7.5 times higher than those who were not exposed. Analysis of variance shows that mean levels of log transformed cotinine in children whose parent(s) smoke in the home, parent(s) who smoke but not in the home, and non-smoking parents are 137.13, 75.60, and 43.28 respectively (p = 0.0009), indicating decreasing levels of cotinine as reported exposure decreases. Using a cut-point of 30 ng/mg of cotinine to differentiate unexposed and exposed to ETS, we found 80% agreement with our survey. A Spearman's ranked correlation coefficient of 0.62 indicates a direct relationship between cotinine and an ETS exposure intensity score (p < 0.0001). CONCLUSIONS: These results suggest that the 5-question survey reflects the child's exposure to passive smoke and that the survey is sensitive to varying levels of exposure.