| 1. |
- Aberg, Fredrik, et al.
(författare)
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A Dynamic Aspartate-to-Alanine Aminotransferase Ratio Provides Valid Predictions of Incident Severe Liver Disease
- 2021
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Ingår i: HEPATOLOGY COMMUNICATIONS. - : John Wiley & Sons. - 2471-254X. ; 5:6, s. 1021-1035
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Tidskriftsartikel (refereegranskat)abstract
- The aspartate-to-alanine aminotransferase ratio (AAR) is associated with liver fibrosis, but its predictive performance is suboptimal. We hypothesized that the association between AAR and liver disease depends on absolute transaminase levels and developed and validated a model to predict liver-related outcomes in the general population. A Cox regression model based on age, AAR, and alanine aminotransferase (ALT) level (dynamic AAR [dAAR]) using restricted cubic splines was developed in Finnish population-based health-examination surveys (FINRISK, 2002-2012; n = 18,067) with linked registry data for incident liver-related hospitalizations, hepatocellular carcinoma, or liver death. The model was externally validated for liver-related outcomes in a Swedish population cohort (Swedish Apolipoprotein Mortality Risk [AMORIS] subcohort; n = 126,941) and for predicting outcomes and/or prevalent fibrosis/cirrhosis in biopsied patients with nonalcoholic fatty liver disease (NAFLD), chronic hepatitis C, or alcohol-related liver disease (ALD). The dynamic AAR model predicted liver-related outcomes both overall (optimism-corrected C-statistic, 0.81) and in subgroup analyses of the FINRISK cohort and identified persons with >10% risk for liver-related outcomes within 10 years. In independent cohorts, the C-statistic for predicting liver-related outcomes up to a 10-year follow-up was 0.72 in the AMORIS cohort, 0.81 in NAFLD, and 0.75 in ALD. Area-under-the-curve (AUC) for detecting prevalent cirrhosis was 0.80-0.83 in NAFLD, 0.80 in hepatitis C, but only 0.71 in ALD. In ALD, model performance improved when using aspartate aminotransferase instead of ALT in the model (C-statistic, 0.84 for outcome; AUC, 0.82 for prevalent cirrhosis). Conclusion: A dAAR score provides prospective predictions for the risk of incident severe liver outcomes in the general population and helps detect advanced liver fibrosis/cirrhosis. The dAAR score could potentially be used for screening the unselected general population and as a trigger for further liver evaluations.
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| 2. |
- Andrén Aronsson, Carin, et al.
(författare)
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25(OH)D Levels in Infancy Is Associated With Celiac Disease Autoimmunity in At-Risk Children : A Case–Control Study
- 2021
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Ingår i: Frontiers in Nutrition. - : Frontiers Media SA. - 2296-861X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: An observed variation in the risk of celiac disease, according to the season of birth, suggests that vitamin D may affect the development of the disease. The aim of this study was to investigate if vitamin D concentration is associated with the risk of celiac disease autoimmunity (CDA) in genetically at-risk children. Study Design: Children prospectively followed in the multinational The Environmental Determinants of Diabetes in the Young study, conducted at six centers in Europe and the US, were selected for a 1-to-3 nested case–control study. In total, 281 case–control sets were identified. CDA was defined as positivity for tissue transglutaminase autoantibodies (tTGA) on two or more consecutive visits. Vitamin D was measured as 25-hydroxyvitamin D [25(OH)D] concentrations in all plasma samples prior to, and including, the first tTGA positive visit. Conditional logistic regression was used to examine the association between 25(OH)D and risk of CDA. Results: No significant association was seen between 25(OH)D concentrations (per 5 nmol/L increase) and risk for CDA development during early infancy (odds ratio [OR] 0.99, 95% confidence interval [CI] 0.95–1.04) or childhood (OR 1.02, 95% CI 0.97–1.07). When categorizing 25(OH)D concentrations, there was an increased risk of CDA with 25(OH)D concentrations <30 nmol/L (OR 2.23, 95% CI 1.29, 3.84) and >75 nmol/L (OR 2.10, 95% CI 1.28–3.44) in early infancy, as compared with 50–75 nmol/L. Conclusion: This study indicates that 25(OH)D concentrations <30 nmol/L and >75 nmol/L during early infancy were associated with an increased risk of developing CDA in genetically at-risk children. The non-linear relationship raises the need for more studies on the possible role of 25(OH)D in the relation to celiac disease onset.
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| 3. |
- Li, Qian, et al.
(författare)
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Plasma Metabolome and Circulating Vitamins Stratified Onset Age of an Initial Islet Autoantibody and Progression to Type 1 Diabetes : the TEDDY Study
- 2021
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 70:1, s. 282-292
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Tidskriftsartikel (refereegranskat)abstract
- Children's plasma metabolome, especially lipidome reflects gene regulation and dietary exposures, heralding the development of islet autoantibodies (IA) and type 1 diabetes (T1D). The TEDDY study enrolled 8676 newborns by screening HLA-DR-DQ genotypes at six clinical centers in four countries; profiled metabolome and measured concentrations of ascorbic acid, 25-hydroxyvitamin D (25(OH)D), erythrocyte membrane fatty acids following birth until IA seroconversion under nested case-control design. We grouped children having an initial autoantibody only against insulin (IAA-first) or glutamic acid decarboxylase (GADA-first) by unsupervised clustering of temporal lipidome, identifying a subgroup of children having early onset of each initial autoantibody, i.e., IAA-first by 12 months and GADA-first by 21 months, consistent with population-wide early seroconversion age. Differential analysis showed that infants having reduced plasma ascorbic acid and cholesterol experienced IAA-first earlier, while early onset of GADA-first was preceded by reduced sphingomyelins at infancy. Plasma 25(OH)D prior to either autoantibody was lower in T1D progressors compared to non-progressors, with simultaneous lower diglycerides, lysophosphatidylcholines, triglycerides, alanine before GADA-first. Plasma ascorbic acid and 25(OH)D at infancy were lower in HLA-DR3/DR4 children among IA cases but not in matched controls, implying gene expression dysregulation of circulating vitamins as latent signals for IA or T1D progression.
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| 4. |
- Niinistö, Sari, et al.
(författare)
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Children's erythrocyte fatty acids are associated with the risk of islet autoimmunity
- 2021
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Our aim was to investigate the associations between erythrocyte fatty acids and the risk of islet autoimmunity in children. The Environmental Determinants of Diabetes in the Young Study (TEDDY) is a longitudinal cohort study of children at high genetic risk for type 1 diabetes (n = 8676) born between 2004 and 2010 in the U.S., Finland, Sweden, and Germany. A nested case-control design comprised 398 cases with islet autoimmunity and 1178 sero-negative controls matched for clinical site, family history, and gender. Fatty acids composition was measured in erythrocytes collected at the age of 3, 6, and 12 months and then annually up to 6 years of age. Conditional logistic regression models were adjusted for HLA risk genotype, ancestry, and weight z-score. Higher eicosapentaenoic and docosapentaenoic acid (n - 3 polyunsaturated fatty acids) levels during infancy and conjugated linoleic acid after infancy were associated with a lower risk of islet autoimmunity. Furthermore, higher levels of some even-chain saturated (SFA) and monounsaturated fatty acids (MUFA) were associated with increased risk. Fatty acid status in early life may signal the risk for islet autoimmunity, especially n - 3 fatty acids may be protective, while increased levels of some SFAs and MUFAs may precede islet autoimmunity.
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