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- Anand, Vibha, et al.
(författare)
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Islet Autoimmunity and HLA Markers of Presymptomatic and Clinical Type 1 Diabetes : Joint Analyses of Prospective Cohort Studies in Finland, Germany, Sweden, and the U.S
- 2021
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 44, s. 2269-2276
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To combine prospective cohort studies, by including HLA harmonization, and estimate risk of islet autoimmunity and progression to clinical diabetes.RESEARCH DESIGN AND METHODS: For prospective cohorts in Finland, Germany, Sweden, and the U.S., 24,662 children at increased genetic risk for development of islet autoantibodies and type 1 diabetes have been followed. Following harmonization, the outcomes were analyzed in 16,709 infants-toddlers enrolled by age 2.5 years.RESULTS: In the infant-toddler cohort, 1,413 (8.5%) developed at least one autoantibody confirmed at two or more consecutive visits (seroconversion), 865 (5%) developed multiple autoantibodies, and 655 (4%) progressed to diabetes. The 15-year cumulative incidence of diabetes varied in children with one, two, or three autoantibodies at seroconversion: 45% (95% CI 40-52), 85% (78-90), and 92% (85-97), respectively. Among those with a single autoantibody, status 2 years after seroconversion predicted diabetes risk: 12% (10-25) if reverting to autoantibody negative, 30% (20-40) if retaining a single autoantibody, and 82% (80-95) if developing multiple autoantibodies. HLA-DR-DQ affected the risk of confirmed seroconversion and progression to diabetes in children with stable single-autoantibody status. Their 15-year diabetes incidence for higher- versus lower-risk genotypes was 40% (28-50) vs. 12% (5-38). The rate of progression to diabetes was inversely related to age at development of multiple autoantibodies, ranging from 20% per year to 6% per year in children developing multipositivity in ≤2 years or >7.4 years, respectively.CONCLUSIONS: The number of islet autoantibodies at seroconversion reliably predicts 15-year type 1 diabetes risk. In children retaining a single autoantibody, HLA-DR-DQ genotypes can further refine risk of progression.
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| 2. |
- Gil, Elisabeth G., et al.
(författare)
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Oral health-related quality of life in 4–16-year-olds with and without juvenile idiopathic arthritis
- 2022
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Ingår i: BMC Oral Health. - : Springer Science and Business Media LLC. - 1472-6831. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Few studies have investigated oral health-related quality of life (OHRQoL) in young individuals with juvenile idiopathic arthritis (JIA). Aims were to investigate whether OHRQoL differs between children and adolescents with JIA compared to controls without JIA, while adjusting for socio-demographic-, behavioral- and oral health-related covariates. Furthermore, to explore whether socio-behavioral and oral health-related covariates of OHRQoL vary according to group affiliation and finally, specifically for individuals with JIA, to investigate whether disease-specific features associate with OHRQoL. We hypothesized that participants with JIA have poorer OHRQoL compared to participants without JIA. Methods: In this comparative cross-sectional study participants with JIA (n = 224) were matched to controls without JIA (n = 224). OHRQoL was assessed according to Early Childhood Oral Health Impact Scale (ECOHIS) (4–11-years-olds) and the child version of Oral Impacts on Daily Performances (Child-OIDP) (12–16-years-olds). JIA-specific characteristics were assessed by pediatric rheumatologists and socio-demographic, behavioral and self-reported oral health information collected by questionnaires. Index teeth were examined for caries by calibrated dentists. Multiple variable analyses were performed using logistic regression, reporting odds ratio (OR) and 95% confidence interval (CI). Two-way interactions were tested between group affiliation and the socio-behavioral- and oral health-related variables on the respective outcome variables. Results: In total, 96 participants with JIA and 98 controls were evaluated according to ECOHIS, corresponding numbers for Child-OIDP was 125 and 124. Group affiliation was not associated with impaired ECOHIS or Child-OIDP in adjusted analyses (OR = 1.95, 95% CI 0.94–4.04 and OR = 0.99, 95% CI 0.46–2.17, respectively). Female adolescents with JIA were more likely than males to report oral impacts according to Child-OIDP. Continued activity or flare was found to adversely affect Child-OIDP, also self-reported outcome measures in JIA associated with Child-OIDP. Conclusions: This study did not provide consistent evidence to confirm the hypothesis that children and adolescents with JIA are more likely to have impaired OHRQoL compared to their peers without JIA. However, female adolescents with JIA were more likely than males to report impacts on OHRQoL. Furthermore, within the JIA group, adolescents with continued disease activity, flare or reporting pain, physical disability, had higher risk than their counterparts of impaired OHRQoL.
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| 3. |
- Halbig, Josefine M., et al.
(författare)
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Oral health-related quality of life, impaired physical health and orofacial pain in children and adolescents with juvenile idiopathic arthritis – a prospective multicenter cohort study
- 2023
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Ingår i: BMC Oral Health. - 1472-6831. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Knowledge on oral health-related quality of life (OHRQoL) in children and adolescents with juvenile idiopathic arthritis (JIA) is limited, and longitudinal studies are lacking. We aimed to describe OHRQoL in children and adolescents with JIA compared to controls, and to explore the validity and internal consistency of the Early Childhood Oral Health Impact Scale (ECOHIS) and the Child Oral Impact on Daily Performance (Child-OIDP). Furthermore, we wanted to investigate associations between OHRQoL and orofacial pain, physical health, disease activity, and temporomandibular joint (TMJ) involvement in JIA. Methods: The Norwegian prospective, multicenter cohort study recruited participants with JIA between 4 and 16years of age and corresponding controls from three pediatric university hospital departments and public dental health services. In the present study, we analyzed OHRQoL in all children < 12years with the ECOHIS and adolescents ≥ 12years with the Child-OIDP at the first visit and the two-year follow-up. Associations between OHRQoL and JIA characteristics, collected in clinical exam and questionnaires, were analyzed in logistic regressions. Results: The same OHRQoL questionnaire was completed both at first visit and two-year follow-up in 101 children < 12years (47 JIA, 54 controls) and 213 adolescents ≥ 12years (111 JIA, 102 controls). The frequency of OHRQoL impacts in children was similar at the first visit and the two-year follow-up (ECOHIS > 0: JIA group 81% and 85%, p = 0.791; control group 65% and 69%, p = 0.815), while adolescents with JIA reported fewer impacts at the two-year follow-up (Child OIDP > 0: JIA group 27% and 15%, p = 0.004; control group 21% and 14%, p = 0.230). The internal consistency of the OHRQoL instruments was overall acceptable and the criterion validity indicated that the instruments were valid at both visits. Orofacial pain was more frequent in children and adolescents with JIA than in controls. We found associations between OHRQoL impacts and orofacial pain, impaired physical health, disease activity, and TMJ involvement. Conclusions: Children and adolescents with orofacial pain or impaired physical health were more likely to report impacts on daily life activities than those without. Pediatric rheumatologists and dentists should be aware of impaired OHRQoL in individuals with JIA with active disease or temporomandibular joint involvement. Trial registration: Registered on clinicaltrials.gov(NCT03904459, 05/04/2019).
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| 5. |
- Jönsson, Josefine, et al.
(författare)
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Lifestyle Intervention in Pregnant Women With Obesity Impacts Cord Blood DNA Methylation, Which Associates With Body Composition in the Offspring
- 2021
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 70:4, s. 854-866
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Tidskriftsartikel (refereegranskat)abstract
- Maternal obesity may lead to epigenetic alterations in the offspring and might thereby contribute to disease later in life. We investigated whether a lifestyle intervention in pregnant women with obesity is associated with epigenetic variation in cord blood and body composition in the offspring. Genome-wide DNA methylation was analyzed in cord blood from 208 offspring from the Treatment of Obese Pregnant women (TOP)-study, which includes pregnant women with obesity randomized to lifestyle interventions comprised of physical activity with or without dietary advice versus control subjects (standard of care). DNA methylation was altered at 379 sites, annotated to 370 genes, in cord blood from offspring of mothers following a lifestyle intervention versus control subjects (false discovery rate [FDR] <5%) when using the Houseman reference-free method to correct for cell composition, and three of these sites were significant based on Bonferroni correction. These 370 genes are overrepresented in gene ontology terms, including response to fatty acids and adipose tissue development. Offspring of mothers included in a lifestyle intervention were born with more lean mass compared with control subjects. Methylation at 17 sites, annotated to, for example, DISC1, GBX2, HERC2, and HUWE1, partially mediates the effect of the lifestyle intervention on lean mass in the offspring (FDR <5%). Moreover, 22 methylation sites were associated with offspring BMI z scores during the first 3 years of life (P < 0.05). Overall, lifestyle interventions in pregnant women with obesity are associated with epigenetic changes in offspring, potentially influencing the offspring's lean mass and early growth.
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| 7. |
- Rönn, Tina, et al.
(författare)
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Circulating triglycerides are associated with human adipose tissue DNA methylation of genes linked to metabolic disease
- 2023
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 32:11, s. 1875-1887
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Tidskriftsartikel (refereegranskat)abstract
- Dysregulation of circulating lipids is a central element for the metabolic syndrome. However, it is not well established whether human subcutaneous adipose tissue is affected by or affect circulating lipids through epigenetic mechanisms. Hence, our aim was to investigate the association between circulating lipids and DNA methylation levels in human adipose tissue. DNA methylation and gene expression were analysed genome-wide in subcutaneous adipose tissue from two different cohorts, including 85 men and 93 women, respectively. Associations between DNA methylation and circulating levels of triglycerides, low-density lipoprotein, high-density lipoprotein and total cholesterol were analysed. Causal mediation analyses tested if adipose tissue DNA methylation mediates the effects of triglycerides on gene expression or insulin resistance. We found 115 novel associations between triglycerides and adipose tissue DNA methylation, e.g. in the promoter of RFS1, ARID2 and HOXA5 in the male cohort (P ≤ 1.1 × 10-7), and 63 associations, e.g. within the gene body of PTPRN2 and COL6A3 in the female cohort. We further connected these findings to altered mRNA expression levels in adipose tissue (e.g. HOXA5, IL11 and FAM45B). Interestingly, there was no overlap between methylation sites associated with triglycerides in men and the sites found in women, which points towards sex-specific effects of triglycerides on the epigenome. Finally, a causal mediation analysis provided support for adipose tissue DNA methylation as a partial mediating factor between circulating triglycerides and insulin resistance. This study identified novel epigenetic alterations in adipose tissue associated with circulating lipids. Identified epigenetic changes seem to mediate effects of triglycerides on insulin resistance.
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