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- Andersson White, Pär, 1983-
(författare)
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Social Inequalities in Child Health : Type 1 Diabetes, Obesity, Cardiovascular Risk Factors and the Role of Self-control
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The Swedish Commission on Health Inequality defined health inequality as systematic differences in health between groups in society with different social positions. All avoidable socioeconomic health inequalities are unfair, and as stated by WHO's Commission on the Social Determinants of Health, we have a moral obligation to try to reduce them. "Putting these inequities right is a matter of social justice. Reducing health inequities is, for the Commission on Social Determinants of Health, an ethical imperative." This ethical imperative is especially apparent regarding the health of children and adolescents. Children’s right to the highest attainable standard of health is also enshrined in Article 24 of the Convention on the Rights of the Child. To reach the goal of a reduction of health inequalities, research is necessary to describe the social gradients of health. Research is also needed to better understand why these gradients occur. A better understanding and knowledge about health inequalities can lead to policies that reduce these inequalities and ensure children’s right to health.This thesis investigates social inequality in child health using data from a Swedish population-based prospective birth cohort, the All Babies in Southeast Sweden (ABIS) cohort. Social inequality in obesity in the ABIS cohort is also compared with other birth cohorts participating in the Elucidating Pathways to Child Health Inequality (EPOCH) collaboration which includes cohorts from six high-income countries; Sweden, the Netherlands, Canada (one national and one cohort from Quebec), UK, Australia, and USA.In Paper 1 we show that health inequalities in overweight and obesity are detectable already at two years of age and that these inequalities increase during childhood. In adolescents, low socioeconomic status increases the risk of becoming overweight and the risk of components of the metabolic syndrome, including high blood pressure and dyslipidemia (low high-density cholesterol).The level of inequality in obesity in the Swedish ABIS cohort was lower than in the other participating countries in the EPOCH collaboration (Paper 2). Inequality was lower in absolute and relative terms when SES was measured by household income. Inequality was also lower in absolute, but not relative, terms when SES was measured by maternal education. This finding indicates that some of the policies implemented in Sweden may attenuate social inequalities in obesity in children. Examples of such policies with evidence for reducing social inequality in obesity implemented in Sweden include universal preschools and free school meals.This thesis also investigates health inequalities in autoimmune disease (Paper 3). In this study, we found that low socioeconomic status increased the risk of Type 1 Diabetes but not the other autoimmune diseases investigated. Path analysis indicated that part of the increased risk in children with low SES of Type 1 Diabetes might be mediated by a higher body mass index and an elevated risk of serious life events.In the final paper, this thesis tests the hypothesis that differences in maternal and child self-control mediate social inequalities in obesity. Two measures of self-control were used; for mothers, the self-control variable was based on behaviors related to self-control (smoking during pregnancy, smoking during the child’s first year of life, breastfeeding duration, and participating in the ABIS study with biological samples). For the children, the self-control variable was based on questionnaire data on the impulsivity subscale of the Strengths and Difficulties Questionnaire (SDQ). The results showed that the two measures of self-control mediated 87.5 % of the increased risk of obesity at age 19 years in children with low maternal education and 93 % of the risk if maternal BMI was also included in the selfcontrol variable.In the discussion part of this thesis, the conclusions that can be deduced from understanding the mechanisms of social inequality in child health are discussed. A theory with a central role of self-control for health inequality predicts that social inequality will increase without interventions. In an environment with rising numbers of stimuli of the human reward system, stimuli that also have negative long-term consequences (socalled Limbic traps), child and adolescent health, in general, will decrease. Because of the mechanisms related to SES and self-control, children with low SES will be disproportionally affected. The result of this development will be increasing levels of social inequalities in child health.The discussion also includes implications for policies that may improve health and reduce inequalities. These policies should reduce the exposure of children and adolescents to harmful behaviors/limbic traps. Examples of policies that have this effect include universal preschools for all children, free healthy meals in preschools and schools, increased after-school activities for all children, and longer school days for adolescents with increased hours for physical activity, music, and art. Mobile phones and social media restrictions in schools and policies to reduce use at home should also be implemented. Finally, policies should be implemented to reduce residential and school segregation in the community.
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| 2. |
- Kindgren, Erik, 1977-
(författare)
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Early Life Environmental Risk Factors and Gut Microbiota in Juvenile Idiopathic Arthritis : - More than a gut feeling
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The autoimmune disease juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children, but the cause is not fully established. Only a small percentage (13–18%) of the risk of contracting the disease can be attributed to genetic factors, but environmental factors are believed to be behind most of the risk. An unfavourable composition of gut bacteria has also been suggested as a factor that may increase the risk of developing JIA. Aims: The main aim of this thesis was to study risk factors during fetal life and in the early childhood environment for future onset of JIA. A further aim was to study the composition and importance of the gut microbiota before the onset of JIA. Methods: In the ABIS study, a population-based prospective birth cohort of 17,055 children, data were collected on environmental factors during pregnancy and childhood. We identified 111 individuals with a JIA diagnosis. Environmental factors were mainly analysed using multivariable logistic regression, with adjustment for confounding factors. The microbiome at one year of age was analysed from stool samples by 16S rRNA PCR. Results: Significant associations could be noted between mode of birth, duration of breastfeeding, birth order and exposure to antibiotics or fish early in life with future onset of JIA. These risk factors were found to pose an even higher cumulative risk if several of the factors were present. Carrying a risk allele in combination with being exposed to a specific environmental factor further increased the risk. In addition, several taxa were identified in the gut microbiota at one year that were associated with future onset of JIA. Many of these taxa were associated with one or more of the identified early childhood environmental risk factors. Conclusion: In these studies, it has been demonstrated that children with JIA have, very early in life, already been exposed to negative environmental factors (caesarean section, short-term breastfeeding, being firstborn and being exposed to antibiotics or fish during the first year of life). The effect from these risk factors appears to be to some extent mediated via a changed composition of the gut microbiota. An environmentally induced dysregulation of the microbiome can trigger or accelerate the development of JIA in genetically predisposed children.
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| 3. |
- Bélteky, Malin, et al.
(författare)
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Infant gut microbiome composition correlated with type 1 diabetes acquisition in the general population: the ABIS study
- 2023
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Ingår i: Diabetologia. - : SPRINGER. - 0012-186X .- 1432-0428. ; 66:6, s. 1116-1128
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis While autoantibodies are traditional markers for type 1 diabetes development, we identified gut microbial biomarkers in 1-year-old infants associated with future type 1 diabetes up to 20 years before diagnosis. Methods Infants enrolled in the longitudinal general population cohort All Babies In Southeast Sweden (ABIS) provided a stool sample at a mean age of 12.5 months. Samples (future type 1 diabetes, n=16; healthy controls, n=268) were subjected to 16S ribosomal RNA (rRNA) sequencing and quantitative PCR. Microbial differences at the taxonomic and core microbiome levels were assessed. PICRUSt was used to predict functional content from the 16S rRNA amplicons. Sixteen infants, with a future diagnosis of type 1 diabetes at a mean age of 13.3 +/- 5.4 years, and one hundred iterations of 32 matched control infants, who remained healthy up to 20 years of age, were analysed. Results Parasutterella and Eubacterium were more abundant in healthy control infants, while Porphyromonas was differentially more abundant in infants with future type 1 diabetes diagnosis. Ruminococcus was a strong determinant in differentiating both control infants and those with future type 1 diabetes using random forest analysis and had differing trends of abundance when comparing control infants and those with future type 1 diabetes. Flavonifractor and UBA1819 were the strongest factors for differentiating control infants, showing higher abundance in control infants compared with those with future type 1 diabetes. Alternatively, Alistipes (more abundant in control infants) and Fusicatenibacter (mixed abundance patterns when comparing case and control infants) were the strongest factors for differentiating future type 1 diabetes. Predicted gene content regarding butyrate production and pyruvate fermentation was differentially observed to be higher in healthy control infants. Conclusions/interpretation This investigation suggests that microbial biomarkers for type 1 diabetes may be present as early as 1 year of age, as reflected in the taxonomic and functional differences of the microbial communities. The possibility of preventing disease onset by altering or promoting a healthy gut microbiome is appealing. Data availability The forward and reverse 16S raw sequencing data generated in this study are available through the NCBI Sequence Read Archive under BioProject PRJNA875929. Associated sample metadata used for statistical comparison are available in the source data file. R codes used for statistical comparisons and figure generation are available at: https://github.com/PMilletich/T1D_Pipeline.
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| 4. |
- Hedbrant, Johan, 1959-
(författare)
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Särimner : a computer model for diabetes education
- 1993
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In diabetes mellitus pancreas fails to produce insulin enough to maintain tissue utilisation of blood glucose. To maintain a normalised metabolism many diabetic patients have to provide insulin from injections or an infusion pump. The disease affects some percent of western population.The insulin provided by the patient has to be adjusted to food and physical exercise. This may be achieved by following rules from diabetes professionals, but also by self learning how food, insulin and physical exercise interact and influence the blood glucose. It seems that the patients who have this intuitive knowledge of the interactions are the ones who manages their diabetes treatment best and have the highest quality of life. The learning have, however, been performed by trial and error - to the price of severe inconvenience and bad metabolic control.A combination of computer science and diabetes physiology has resulted in the computer program Särimner. It is created to give the user a possibility to experiment with diabetes treatment. Food, insulin and physical exercise may be varied and the blood glucose is calculated. Sarimner provides a short-cut to obtaining knowledge since it allows experiments, stimulates discussions and let the user by himself formulate and test hypotheses regarding experienced problems. Since Särimner may be adjusted to look more alike an individual, the experiments are driven by the user's own curiosity. He may experiment with situations of importance to himself and finally make himself the expert of his own treatment situation.The way Särimner is designed, allows interested users to get "under the skin" of the model and study details in the physiological processes. This transparency makes it possible to search for explanations to treatment phenomena. One drawback with the model is that it is quite complex and requires some knowledge from a user with the ambition to understand all the processes.To measure the impact of Särimner training, 11 diabetic teenagers were evaluated with respect to metabolic control, emotional adjustment, focus of control, self-esteem and ability to discuss treatment phenomena. No control group was possible to recruit.The results indicated that the education had been useful for some individuals. They increased their knowledge and ability to discuss treatment situations, their sense of control over the diabetes treatment, their self esteem and furthermore Särimner education may have caused a reduction of diabetes related stress. However, an increased level of diabetes related guilt did occur in some individuals, possibly due to either increased knowledge or a more internalised focus of control.The models ability to look alike reality is depending on for which purpose it is used. Even though it would be theoretically possible to fit the model to an individual, such an experiment would not be performable in reality since Särimner requires input data from the physiology which is impossible to measure. The properties of the model are, however, adequate for illustrating several treatment situations on a phenomenological level.
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| 6. |
- Taylor, Peter N, et al.
(författare)
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C-peptide and metabolic outcomes in trials of disease modifying therapy in new-onset type 1 diabetes: an individual participant meta-analysis
- 2023
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Ingår i: The Lancet Diabetes and Endocrinology. - : Elsevier. - 2213-8587 .- 2213-8595. ; 11:12, s. 915-925
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Tidskriftsartikel (refereegranskat)abstract
- Background: Metabolic outcomes in type 1 diabetes remain suboptimal. Disease modifying therapy to prevent β-cell loss presents an alternative treatment framework but the effect on metabolic outcomes is unclear. We, therefore, aimed to define the relationship between insulin C-peptide as a marker of β-cell function and metabolic outcomes in new-onset type 1 diabetes.Methods: 21 trials of disease-modifying interventions within 100 days of type 1 diabetes diagnosis comprising 1315 adults (ie, those 18 years and older) and 1396 children (ie, those younger than 18 years) were combined. Endpoints assessed were stimulated area under the curve C-peptide, HbA1c, insulin use, hypoglycaemic events, and composite scores (such as insulin dose adjusted A1c, total daily insulin, U/kg per day, and BETA-2 score). Positive studies were defined as those meeting their primary endpoint. Differences in outcomes between active and control groups were assessed using the Wilcoxon rank test.Findings: 6 months after treatment, a 24·8% greater C-peptide preservation in positive studies was associated with a 0·55% lower HbA1c (p<0·0001), with differences being detectable as early as 3 months. Cross-sectional analysis, combining positive and negative studies, was consistent with this proportionality: a 55% improvement in C-peptide preservation was associated with 0·64% lower HbA1c (p<0·0001). Higher initial C-peptide levels and greater preservation were associated with greater improvement in HbA1c. For HbA1c, IDAAC, and BETA-2 score, sample size predictions indicated that 2-3 times as many participants per group would be required to show a difference at 6 months as compared with C-peptide. Detecting a reduction in hypoglycaemia was affected by reporting methods.Interpretation: Interventions that preserve β-cell function are effective at improving metabolic outcomes in new-onset type 1 diabetes, confirming their potential as adjuncts to insulin. We have shown that improvements in HbA1c are directly proportional to the degree of C-peptide preservation, quantifying this relationship, and supporting the use of C-peptides as a surrogate endpoint in clinical trials.
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| 7. |
- Tojjar, Jasaman, et al.
(författare)
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Sex Differences in Age of Diagnosis, HLA Genotype, and Autoantibody Profile in Children With Type 1 Diabetes
- 2023
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Ingår i: Diabetes care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 46:11, s. 1993-1996
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To examine sex differences in children with newly diagnosed type 1 diabetes (T1D) with respect to age at diagnosis, presence of autoantibodies (GAD antibody [GADA], insulinoma-associated protein 2 [IA-2A], insulin autoantibody [IAA], and zinc transporter 8 autoantibody), and HLA risk. RESEARCH DESIGN AND METHODS: A population-based nationwide sample of 3,645 Swedish children at T1D diagnosis was used. RESULTS: Girls were younger at T1D diagnosis (9.53 vs. 10.23 years; P < 0.001), more likely to be autoantibody-positive (94.7% vs. 92.0%; P = 0.002), more often positive for multiple autoantibodies (P < 0.001), more likely to be positive for GADA (64.9% vs. 49.0%; P < 0.001), and less likely to be positive for IAA (32.3% vs. 33.8%; P = 0.016). Small sex differences in HLA risk were found in children <9 years of age. CONCLUSIONS: The disease mechanisms leading to T1D may influence the immune system differently in girls and boys.
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