Serum ferritin level is associated with liver fibrosis and incident liver-related outcomes independent of HFE genotype in the general population.

BACKGROUND & AIMS: Hyperferritinemia reflects iron accumulation in the body and has been associated with metabolic disturbances and alcohol use, and is also a common finding in individuals diagnosed with liver disease. The major genetic regulator of iron metabolism is the HFE gene. METHODS: The aim of this this study was to investigate the association between serum ferritin and liver fibrosis using the enhanced liver fibrosis (ELF) test, and the association between ferritin and liver-related outcomes in a Finnish population-based cohort of 6194 individuals (45% male, mean [± standard deviation] age, 52.9 ± 14.9 years; body mass index 26.9 ± 4.7 kg/m2). The effects of HFE variants on these associations were also evaluated. RESULTS: Serum ferritin levels were significantly associated with liver fibrosis, as estimated by enhanced liver fibrosis (ELF) test in weighted linear regression analysis. Serum ferritin was significantly associated with both all liver-related outcomes (n = 92) and severe liver-related outcomes (n = 54) in weighted Cox regression analysis (hazard ratio [HR] per 1 SD, 1.11 [95% confidence interval (CI) 1.02-1.21]; p = 0.012 and HR 1.11 [95% CI 1.02-1.21]; p = 0.013, respectively). However, there was association neither between HFE risk variants and ELF test nor between HFE risk variants and liver-related outcomes. CONCLUSION: Serum ferritin levels were associated with liver fibrosis and incident liver disease, independent of HFE genotype in the general population. Furthermore, data demonstrated that metabolic disturbances and alcohol use were major risk factors for hyperferritinemia.

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.

Moderate associations between the use of levonorgestrel-releasing intrauterine device and metabolomics profile.

CONTEXT: Use of levonorgestrel-releasing intrauterine device (LNG-IUD) has become common irrespective of age and parity. To date, only a few studies have examined its possible metabolic changes and large-scale biomarker profiles in detail and in a longitudinal design. OBJECTIVE: To apply the metabolomics technique to examine the metabolic profile associated with the use of LNG-IUD both in a cross-sectional and in a longitudinal design. DESIGN: The study consists of cross-sectional and longitudinal analyses of a population-based survey (Health 2000) and its 11-year follow-up (Health 2011). All participants aged 18-49 years with available information on hormonal contraceptive use and metabolomics data (n=1767) were included. Altogether 212 metabolic measures in LNG-IUD users (n=341) were compared to those in non-users of hormonal contraception (n=1426) via multivariable linear regression models. Participants with complete longitudinal information (n=240) were divided into continuers, stoppers, starters, and never-user groups, and 11-year changes in levels of each metabolite were compared. RESULTS: After adjustment for covariates, levels of 102 metabolites differed in LNG-IUD current users compared to non-users of hormonal contraception (median difference in biomarker concentration: -0.12 SD): lower levels of fatty acids concentrations and ratios, cholesterol, triglycerides and other lipids, as well as particle concentration, cholesterol, total lipids and phospholipids in lipoproteins. The 11-year metabolic changes did not differ in relation to changes in LNG-IUD use. CONCLUSIONS: The use of LNG-IUD was associated with several moderate metabolic changes, mostly suggestive of a reduced arterial cardiometabolic risk. Changes in LNG-IUD use were not related to long-term metabolic changes.