Intake of B vitamins and the risk of developing islet autoimmunity and type 1 diabetes in the TEDDY study.

PURPOSE: The aim was to study the association between dietary intake of B vitamins in childhood and the risk of islet autoimmunity (IA) and progression to type 1 diabetes (T1D) by the age of 10 years. METHODS: We followed 8500 T1D-susceptible children born in the U.S., Finland, Sweden, and Germany in 2004 -2010 from the Environmental Determinants of Diabetes in the Young (TEDDY) study, which is a prospective observational birth cohort. Dietary intake of seven B vitamins was calculated from foods and dietary supplements based on 24-h recall at 3 months and 3-day food records collected regularly from 6 months to 10 years of age. Cox proportional hazard models were adjusted for energy, HLA-genotype, first-degree relative with T1D, sex, and country. RESULTS: A total of 778 (9.2) children developed at least one autoantibody (any IA), and 335 (3.9%) developed multiple autoantibodies. 280 (3.3%) children had IAA and 319 (3.8%) GADA as the first autoantibody. 344 (44%) children with IA progressed to T1D. We observed that higher intake of niacin was associated with a decreased risk of developing multiple autoantibodies (HR 0.95; 95% CI 0.92, 0.98) per 1 mg/1000 kcal in niacin intake. Higher intake of pyridoxine (HR 0.66; 95% CI 0.46, 0.96) and vitamin B12 (HR 0.87; 95% CI 0.77, 0.97) was associated with a decreased risk of IAA-first autoimmunity. Higher intake of riboflavin (HR 1.38; 95% CI 1.05, 1.80) was associated with an increased risk of GADA-first autoimmunity. There were no associations between any of the B vitamins and the outcomes "any IA" and progression from IA to T1D.  CONCLUSION: In this multinational, prospective birth cohort of children with genetic susceptibility to T1D, we observed some direct and inverse associations between different B vitamins and risk of IA.

Early Probiotic Supplementation and the Risk of Celiac Disease in Children at Genetic Risk.

Probiotics are linked to positive regulatory effects on the immune system. The aim of the study was to examine the association between the exposure of probiotics via dietary supplements or via infant formula by the age of 1 year and the development of celiac disease autoimmunity (CDA) and celiac disease among a cohort of 6520 genetically susceptible children. Use of probiotics during the first year of life was reported by 1460 children. Time-to-event analysis was used to examine the associations. Overall exposure of probiotics during the first year of life was not associated with either CDA (n = 1212) (HR 1.15; 95%CI 0.99, 1.35; p = 0.07) or celiac disease (n = 455) (HR 1.11; 95%CI 0.86, 1.43; p = 0.43) when adjusting for known risk factors. Intake of probiotic dietary supplements, however, was associated with a slightly increased risk of CDA (HR 1.18; 95%CI 1.00, 1.40; p = 0.043) compared to children who did not get probiotics. It was concluded that the overall exposure of probiotics during the first year of life was not associated with CDA or celiac disease in children at genetic risk.

Role of bicarbonate supplementation on urine uric acid crystals and diabetic tubulopathy in adults with type 1 diabetes.

Uricosuria and crystallization are increasingly recognized risk factors for diabetic tubulopathy. This pilot clinical trial aimed to determine the acute effect of urinary alkalinization using oral sodium bicarbonate (NaHCO3 ) on UA crystals in adults with type 1 diabetes (T1D). Adults with T1D, ages 18 to 65 years (n = 45, 60% female, HbA1c, 7.5 ± 1.2%, 20.2 ± 9.3 years duration) without chronic kidney disease (eGFR ≥60 mL/min/1.73 m2 and albumin-to-creatinine ratio < 30 mg/g) received 2 doses of 1950 mg oral NaHCO3 over 24 hours. Fasting urine and serum were collected pre- and post-intervention. UA crystals were identified under polarized microscopy. Urine measurements included: osmolality, pH, UA, creatinine and kidney injury molecule-1 (KIM-1). NaHCO3 therapy increased mean ± SD urine pH from 6.1 ± 0.7 to 6.5 ± 0.7 (P < .0001). Prior to therapy, 31.0% of participants had UA crystals vs 6.7% post therapy (P = .005). Change in urine pH inversely correlated with change in urine KIM-1 (r:-0.51, P = .0003). In addition, change in urine UA over 24 hours correlated with change in urine KIM-1 (r:0.37, P = .01). In conclusion, oral NaHCO3 normalized urine pH and decreased UA crystals, and may hold promise as an inexpensive and safe tubulo-protective intervention in individuals with T1D.

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.

Urinary F2-isoprostanes in young healthy children at risk for type 1 diabetes mellitus.

Oxidative stress has been linked to many diseases, but little information exists on biomarkers of oxidative stress in healthy children. The purpose of this study was to describe factors that correlate with urinary F2-isoprostanes, an indicator of oxidative stress, and to establish normal concentrations of F2-isoprostanes in children at risk to develop type 1 diabetes mellitus. Creatinine-adjusted urinary F2-isoprostanes were assessed in 342 Denver children under the age of 7 years, from whom we had collected data during 769 clinic visits from August 1997 through January 2001 (mean 2.3 visits per child). Children were identified by newborn screening for HLA-markers, of varying degrees of prediction, for the development of type 1 diabetes. Plasma antioxidants and carotenoids, age at clinic visit, vitamin supplement use, exposure to environmental tobacco smoke, gender, and race were evaluated as correlates to the degree of oxidative stress, using mixed models for longitudinal data. F2-isoprostane levels were highest in infancy and decreased nonlinearly until 7 years. Female gender, HLA-DR3/4 genotype, higher plasma gamma-tocopherol:total lipids ratio, and lower alpha-carotene:total lipids ratio correlated with higher F2-isoprostane levels. Normal values in this healthy population can be used as the basis for future studies of disease mechanisms involving oxidative stress.