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Purpose Methods Results Conclusion Elucidate the prevalence of myopia among young adults from a birth cohort of Swedish children and its relationship to possible risk factors during their childhood.Five thousand two hundred young adults, mean 23.4 years and 58% females, participating in the prospective birth cohort All Babies in Southeast Sweden (ABIS) answered a questionnaire including questions regarding health and physical activity, spectacle use, myopia and age at first optical correction. Questionnaires at previous follow‐ups at ages 2–3, 5–6 and 8 years included information on type of housing, time outdoors, screen time and hours of reading. Myopia prevalence and associations with potential risk factors were analysed in univariate and multivariate regression models with Bonferroni's correction of p‐values.In the ABIS Swedish birth cohort of young adults, the prevalence of myopia was 29%. A univariate logistic regression showed a higher odds ratio for myopia with female gender (OR 1.59; p < 0.05) and a completed and started university education (OR 1.52; p < 0.05). Significantly lower odds ratios were found for hours spent outdoors at 8 years of age (OR 0.82; p < 0.05). Multivariate logistic regression showed a higher odds ratio for myopia in females (OR 1.52–1.57; p < 0.05) and completed and started university education (OR 1.34–1.49; p < 0.05) in all models. In a model including accommodative effort, measured in diopter hours at 8 years of age, hours spent outdoors were associated with a lower odds ratio for myopia (OR 0.86; p < 0.05). No association could be detected between myopia and the type of housing or near work.The prevalence of myopia among young adults in a Swedish birth cohort was lower or unchanged compared to previous data. Female gender, higher education and less time spent outdoors in childhood were associated with an increased risk of developing myopia. Recommendations from child health services and schools should be given to stimulate children to spend enough time outdoors. [ABSTRACT FROM AUTHOR]

The article focuses on recent advancements in treatments for type 1 diabetes, emphasizing the potential of immunologic interventions to preserve residual insulin secretion and improve patient outcomes. It discusses two specific interventions, teplizumab and baricitinib, both showing promise in preserving beta-cell function. It underscores the importance of these treatments in enhancing the quality of life for patients with type 1 diabetes.

The article discusses the need for psychological support for parents of children with type 1 diabetes. Type 1 diabetes is a life-threatening chronic disease that requires intensive daily treatment. The prevalence of depression in parents of children with type 1 diabetes is relatively high, with half of the children having a parent with signs of depression. The article emphasizes the importance of routine assessment of parental depression and the need for more research on fathers. It also highlights the need for psychological support and training for healthcare professionals in managing the psychological well-being of both children and parents. [Extracted from the article]

Aim: Previous studies have reported an association between month of birth and incidence of type 1 diabetes. Using population‐based data, including almost all newly diagnosed children with type 1 diabetes in Sweden, we tested whether month of birth influences the risk of type 1 diabetes. Methods: For 8761 children diagnosed with type 1 diabetes between May 2005 and December 2016 in the Better Diabetes Diagnosis study, month of birth, sex and age were compared. Human leucocyte antigen (HLA) genotype and autoantibodies at diagnosis were analysed for a subset of the cohort (n = 3647). Comparisons with the general population used data from Statistics Sweden. Results: We found no association between month of birth or season and the incidence of type 1 diabetes in the cohort as a whole. However, boys diagnosed before 5 years were more often born in May (p = 0.004). We found no correlation between month of birth and HLA or antibodies. Conclusion: In this large nationwide study, the impact of month of birth on type 1 diabetes diagnosis was weak, except for boys diagnosed before 5 years of age, who were more likely born in May. This may suggest different triggers for different subgroups of patients with type 1 diabetes. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to examine social gradients in ADHD during late childhood (age 9–11 years) using absolute and relative relationships with socioeconomic status exposure (household income, maternal education) during early childhood (<5 years) in seven cohorts from six industrialised countries (UK, Australia, Canada, The Netherlands, USA, Sweden). Methods: Secondary analyses were conducted for each birth cohort. Risk ratios, pooled risk estimates, and absolute inequality, measured by the Slope Index of Inequality (SII), were estimated to quantify social gradients in ADHD during late childhood by household income and maternal education measured during early childhood. Estimates were adjusted for child sex, mother age at birth, mother ethnicity, and multiple births. Findings: All cohorts demonstrated social gradients by household income and maternal education in early childhood, except for maternal education in Quebec. Pooled risk estimates, relating to 44,925 children, yielded expected gradients (income: low 1.83(CI 1.38,2.41), middle 1.42(1.13,1.79), high (reference); maternal education: low 2.13(1.39,3.25), middle 1.42(1.13,1.79)). Estimates of absolute inequality using SII showed that the largest differences in ADHD prevalence between the highest and lowest levels of maternal education were observed in Australia (4% lower) and Sweden (3% lower); for household income, the largest differences were observed in Quebec (6% lower) and Canada (all provinces: 5% lower). Conclusion: Findings indicate that children in families with high household income or maternal education are less likely to have ADHD at age 9–11. Absolute inequality, in combination with relative inequality, provides a more complete account of the socioeconomic status and ADHD relationship in different high-income countries. While the study design precludes causal inference, the linear relation between early childhood social circumstances and later ADHD suggests a potential role for policies that promote high levels of education, especially among women, and adequate levels of household income over children's early years in reducing risk of later ADHD. [ABSTRACT FROM AUTHOR]

Objective: The β‐cell stress hypothesis suggests that increased insulin demand contributes to the development of type 1 diabetes. In the TRIGR trial we set out to assess the profile of plasma glucose and HbA1c before the diagnosis of clinical diabetes compared to nondiabetic children. Research Design and Methods: A cohort of children (N = 2159) with an affected first‐degree relative and increased HLA risk were recruited 2002–2007 and followed until 2017. To study the relationship between plasma glucose/HbA1c and the development of autoantibodies or clinical disease Kaplan‐Meir curves were developed. Mixed models were constructed for plasma glucose and HbA1c separately. Results: A family history of type 2 diabetes was related to an increase in plasma glucose (p < 0.001). An increase in glucose from the previous sample predicted clinical diabetes (p < 0.001) but not autoantibodies. An increase of HbA1c of 20% or 30% from the previous sample predicted the development of any autoantibody (p < 0.003 resp <0.001) and the development of diabetes (p < 0.002 resp <0.001. Participants without autoantibodies had lower HbA1c (mean 5.18%, STD 0.24; mean 33.08 mmol/mol, STD 2.85) than those who progressed to clinical disease (5.31%, 0.42; 34.46 mmol/mol, 4.68; p < 0.001) but higher than those who developed any autoantibody (5.10%, 0.30; 32.21 mmol/mol, 3.49; p < 0.001), or multiple autoantibodies (5.11%, 0.35; 32.26 mmol/mol, 3.92; p < 0.003). Conclusions: A pronounced increase in plasma glucose and HbA1c precedes development of clinical diabetes, while the association between plasma glucose or HbA1c and development of autoantibodies is complex. Increased insulin demand may contribute to development of type 1 diabetes. [ABSTRACT FROM AUTHOR]

Background: One of the most important protective health factors for children is breast-feeding, but the mechanisms for this effect are not fully elucidated. Our objective was to assess if the duration of breastfeeding influences cortisol in hair, used as a biomarker for stress in children still at school-age. Methods: ABIS (All Babies in Southeast Sweden) is a prospective population-based child cohort study of 17,055 children born Oct 1st1997- Oct 1st 1999, with the aim to study development of immune-mediated diseases. Questionnaires were answered at birth and then at regular follow-ups, and biological samples were collected. As a biomarker of stress, we measured the child's cortisol in hair collected at 8 years of age, those randomly selected N = 126 children among those with enough hair samples for analyses of hair at 8 years of age. Duration of breastfeeding had been registered as well as psycho-social factors related to breastfeeding and/or stress. Results: There was a negative correlation (r = − 0.23, p = 0.01) between total duration of breastfeeding and hair cortisol levels at 8 years of age. In a multivariate analysis this association persisted (p = 0.01) even when adjusted for other potential intervening factors like age of mother at delivery and early psychosocial vulnerability in the family, an index based on 11 factors (Multivariate model: df = 5, adj R2 = 0.15, F = 5.38, p < 0.01). Conclusion: Our results show that longer breastfeeding is associated with lower cortisol levels in the child many years later. These associations should be more elaborated in further studies, and these findings also give some implications for public health. Mothers should be encouraged to breastfeed their children also in the modern society, since breastfeeding promotes health in the child. This information could be given via the obstetric departments and later at the well-baby clinics. [ABSTRACT FROM AUTHOR]

Background: The aetiology of juvenile idiopathic arthritis (JIA) is poorly understood. It has been shown that use of antibiotics is associated with JIA. However, whether the association is due to increased occurrence of infection in these individuals is unknown. The purpose of this investigation was to measure the association between number of infections and use of antibiotics during childhood with development of JIA. Methods: In ABIS (All Babies in Southeast Sweden) a population-based prospective birth cohort of 17,055 children, data were collected on infections and antibiotic exposure during pregnancy and childhood. 102 individuals with JIA were identified. Multivariable logistic regression analyses were performed, adjusting for confounding factors. Results: Exposure to antibiotics during the periods 1–12 months, 1–3 years and 5–8 years was significantly associated with increased risk for JIA. The odds of developing JIA were three times higher in those exposed to antibiotics during the first 3 years of life compared with those not exposed (aOR 3.17; 95% CI 1.11–9.03, p = 0.031), and more than twice as high in those exposed to antibiotics during the first 5 years of life compared with those not exposed (aOR 2.18; 95% CI 1.36–3.50, p = 0.001). The odds of developing JIA were 78% higher in those exposed to antibiotics during the first 8 years of life compared with those not exposed (aOR 1.78; 95% CI 1.15–2.73, p = 0.009). Occurrence of infection during fetal life or childhood showed no significant association with the risk of developing JIA, after confounder adjustment. The cumulative number of courses of antibiotics was significantly higher during childhood for the individuals who developed JIA (p < 0.001). Penicillins were more frequently used than non-penicillins, but both had an equal effect on the risk of developing JIA. Conclusions: Exposure to antibiotics early in life is associated with later onset of JIA in a large birth cohort from the general population. The relationship was dose dependent. These results suggest that further, more restrictive, antibiotic policies during the first years of life would be advisable. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy of aluminum-formulated intralymphatic glutamic acid decarboxylase (GAD-alum) therapy combined with vitamin D supplementation in preserving endogenous insulin secretion in all patients with type 1 diabetes (T1D) or in a genetically prespecified subgroup.Research Design and Methods: In a multicenter, randomized, placebo-controlled, double-blind trial, 109 patients aged 12-24 years (mean ± SD 16.4 ± 4.1) with a diabetes duration of 7-193 days (88.8 ± 51.4), elevated serum GAD65 autoantibodies, and a fasting serum C-peptide >0.12 nmol/L were recruited. Participants were randomized to receive either three intralymphatic injections (1 month apart) with 4 μg GAD-alum and oral vitamin D (2,000 IE daily for 120 days) or placebo. The primary outcome was the change in stimulated serum C-peptide (mean area under the curve [AUC] after a mixed-meal tolerance test) between baseline and 15 months.Results: Primary end point was not met in the full analysis set (treatment effect ratio 1.091 [CI 0.845-1.408]; P = 0.5009). However, GAD-alum-treated patients carrying HLA DR3-DQ2 (n = 29; defined as DRB1*03, DQB1*02:01) showed greater preservation of C-peptide AUC (treatment effect ratio 1.557 [CI 1.126-2.153]; P = 0.0078) after 15 months compared with individuals receiving placebo with the same genotype (n = 17). Several secondary end points showed supporting trends, and a positive effect was seen in partial remission (insulin dose-adjusted HbA1c ≤9; P = 0.0310). Minor transient injection site reactions were reported.Conclusion: Intralymphatic administration of GAD-alum is a simple, well-tolerated treatment that together with vitamin D supplementation seems to preserve C-peptide in patients with recent-onset T1D carrying HLA DR3-DQ2. This constitutes a disease-modifying treatment for T1D with a precision medicine approach. [ABSTRACT FROM AUTHOR]

This article examines the relationship between weight and the development of retinopathy in individuals with type 1 diabetes. The study, conducted in Sweden, found that individuals with overweight or obesity have an increased risk of retinopathy, regardless of subsequent weight changes. However, after adjusting for other factors, the increased risk associated with a history of overweight or obesity was no longer significant. The study emphasizes the importance of weight management programs for individuals with type 1 diabetes to reduce the risk of retinopathy. [Extracted from the article]

Background: Insulitis in type 1 diabetes (T1D) seems to be both mild and rather rare, and immune cells are found also in the exocrine pancreas, which often is small. We wanted to see whether clinical pancreatitis at diagnosis of T1D in children is a commonly missed diagnosis. Methods: Clinical symptoms suggesting pancreatitis were investigated in a retrospective case‐control study in 191 newly diagnosed T1D patients (105 boys, 86 girls) with age at onset 0.2 to 18 (mean = 10.05, SD = 4.71, median = 10.36) years, 23/191 (12%) with ketoacidosis at diagnosis. Blood samples were taken on day 4 and stored at −20°C until analyses for P‐amylase and C‐reactive protein (CRP), and compared with 100 age‐matched healthy control children with plasma stored at −80°C, and 46 with plasma stored at −20°C. Results: At diagnosis, 23/191 (12%) patients had mild transient abdominal pain, 2/23 with obstipation, and 5/23 also transient mild diarrhea. Five of 23 patients with abdominal pain had pH < 7.30. None had clinical acute pancreatitis. One diabetic patient had P‐amylase 1.3 μkat/L (normal range = 0.15‐1.1 μkat/L), while 62/191 (32.4%) diabetic children had P‐amylase below the normal range. None (0/100) of the −80‐controls and only 1/46 (0.14 μkat/L) of the −20‐controls had the P‐amylase level in the normal range. Five diabetic children, but no controls, had increased CRP, but not related to P‐amylase or to gastrointestinal symptoms. Conclusions: Acute pancreatitis seems to be very rare at diagnosis of T1D, but decreased exocrine function quite common, which supports that T1D sometimes is part of a more generalized pancreatic disorder. [ABSTRACT FROM AUTHOR]

Background: The autoimmune process later leading to type 1 diabetes (T1D) seems to start very early in life. Different viruses have been suspected to contribute to the development of T1D, some already during pregnancy. As viruses may be hosted by animals and from them transferred to humans we decided to investigate if exposure to pets during pregnancy is related to later development of T1D. Methods: ABIS (All Babies in Southeast Sweden)—is a prospective population‐based cohort study of unselected children born in southeast Sweden between Oct first 1997 to Oct first 1999. Parents of 16 384 children answered a questionnaire within 3 days after birth including information about exposure to different pets. The ABIS registry has been connected to the National Registry of diagnosis and also the national Registry of Drug prescriptions so we know that 137 children have got T1D, and they were compared with the non‐diabetic population. Results: During pregnancy, 45.5% of the mothers had pet animals at home. Most common were cats (25.0%) and dogs (18.7%). Neither exposure to dogs (OR = 1.27, P = 0.23) or cats (OR = 0.81, P = 0.31) were associated to later T1D risks. However, exposure to hamsters increased the T1D risk (OR 4.21, P = 0.0007). In a multiple regression this association remained (P = 0.005) when adjusted for other possible risk factors. Conclusions: Exposure to hamster during pregnancy seems to increase the risk of T1D in the child. One possibility could be infection by virus hosted by the pet. [ABSTRACT FROM AUTHOR]

Objectives: C-peptide (CP) loss in type 1 diabetes (T1D) is highly variable, and factors influencing it are poorly understood. We modelled CP values in T1D patients from diagnosis for up to 6 years, treating the serial data as growth curves plotted against time since diagnosis. The aims were to summarise the pattern of CP loss (i.e. growth curve shape) in individual patients in simple terms, and to identify baseline characteristics that predict this pattern in individuals. Materials and methods: Between 1976 and 2011, 442 T1D patients initially aged <18y underwent 120-minute mixed meal tolerance tests (MMTT) to calculate area under the curve (AUC) CP, at 3, 9, 18, 30, 48 and 72 months after diagnosis (n = 1537). The data were analysed using the novel SITAR mixed effects growth curve model (SuperImposition by Translation And Rotation). It fits a mean AUC growth curve, but also allows the curve’s mean level and rate of fall to vary between individuals so as to best fit the individual patient curves. These curve adjustments define individual curve shape. Results: The square root (√) AUC scale provided the best fit. The mean levels and rates of fall for individuals were normally distributed and uncorrelated with each other. Age at diagnosis and √AUC at 3 months strongly predicted the patient-specific mean levels, while younger age at diagnosis (p<0.0001) and the 120-minute CP value of the 3-month MMTT (p = 0.002) predicted the patient-specific rates of fall. Conclusions: SITAR growth curve analysis is a useful tool to assess CP loss in type 1 diabetes, explaining patient differences in terms of their mean level and rate of fall. A definition of rapid CP loss could be based on a quantile of the rate of fall distribution, allowing better understanding of factors determining CP loss and stratification of patients into targeted therapies. [ABSTRACT FROM AUTHOR]

Objective: To describe the introduction of complementary foods in a populationbased cohort in relation to recommendations and explore the possible impact of maternal education on infant feeding practices. Design: Prospective data from the All Babies in Southeast Sweden (ABIS) cohort study were used. The ABIS study invited all infants born in south-east Sweden during October 1997-October 1999 (n 21 700) to participate. A questionnaire was completed for 16 022 infants. During the infants' first year parents continuously filed in a diary covering introduction of foods. Setting: Sweden. Subjects: Infants (n 9727) with completed food diaries. Results: Potatoes, vegetables, fruits/berries and porridge were the foods first introduced, with a median introduction between 19 and 22 weeks, followed by introduction of meat, cow's milk, follow-on formula and sour milk/yoghurt between 24 and 27 weeks. Early introduction of any food, before 16 weeks, occurred for 27% of the infants and was more common in infants of mothers with low education. Overall, potatoes (14·7 %), vegetables (11·1 %), fruits/berries (8·5 %), porridge (7·4%) and follow-on formula (2·7%) were the foods most frequently introduced early. The majority of infants (=70 %) were introduced to potatoes, vegetables, fruits/berries and porridge during concurrent breast-feeding, but introduction during concurrent breast-feeding was less common in infants of mothers with low education. Conclusions: Most infants were introduced to complementary foods timely in relation to recommendations. Low maternal education was associated with earlier introduction of complementary foods and less introduction during concurrent breast-feeding. Still, the results indicated exposure to fewer foods at 12 months in infants of mothers with low education. [ABSTRACT FROM AUTHOR]

Objective: To describe the introduction of complementary foods in a population-based cohort in relation to recommendations and explore the possible impact of maternal education on infant feeding practices.Design: Prospective data from the All Babies in Southeast Sweden (ABIS) cohort study were used. The ABIS study invited all infants born in south-east Sweden during October 1997-October 1999 (n 21 700) to participate. A questionnaire was completed for 16 022 infants. During the infants' first year parents continuously filed in a diary covering introduction of foods.Setting: Sweden.Subjects: Infants (n 9727) with completed food diaries.Results: Potatoes, vegetables, fruits/berries and porridge were the foods first introduced, with a median introduction between 19 and 22 weeks, followed by introduction of meat, cow's milk, follow-on formula and sour milk/yoghurt between 24 and 27 weeks. Early introduction of any food, before 16 weeks, occurred for 27 % of the infants and was more common in infants of mothers with low education. Overall, potatoes (14·7 %), vegetables (11·1 %), fruits/berries (8·5 %), porridge (7·4 %) and follow-on formula (2·7 %) were the foods most frequently introduced early. The majority of infants (≥70 %) were introduced to potatoes, vegetables, fruits/berries and porridge during concurrent breast-feeding, but introduction during concurrent breast-feeding was less common in infants of mothers with low education.Conclusions: Most infants were introduced to complementary foods timely in relation to recommendations. Low maternal education was associated with earlier introduction of complementary foods and less introduction during concurrent breast-feeding. Still, the results indicated exposure to fewer foods at 12 months in infants of mothers with low education. [ABSTRACT FROM AUTHOR]

Worm infestations influence the immune system and may therefore decrease the risk for autoimmune diseases. The aim of the study was to determine whether children who have developed autoimmune disease were less likely to have had worm infestations in childhood. The ABIS-study is a prospective population-based cohort study of children born in southeast Sweden 1997/99. 17.055 children participated. As of June 2014 116 individuals had developed Type 1 diabetes, 181 celiac disease, and 53 Juvenile Rheumatoid Arthritis. The parents answered questions on worm infestations when the children were 1, 5 and 8 years of age. The ABIS registry was connected to the National Registry of Drug Prescriptions, and national registries for diagnosis of the studied diseases. We found no differences in incidence of worm infestations at 1, 5 or 8 years of age between children who developed autoimmune disease(s) or healthy controls. At 8 years in total 20.0% of the general child population had experienced a worm infestation; children who developed Type 1 diabetes, 21,3%, celiac disease 19,5% and JRA 18,8%. There was no difference in prescriptions of drugs for treatment of worm infestations between those who had and who had not developed Type 1 diabetes, celiac disease, Juvenile Rheumatoid Arthritis. We found no associations indicating that worm infestations in childhood does not play a role in the development of autoimmune diseases in Sweden. [ABSTRACT FROM AUTHOR]

The incidence of type 1 diabetes has risen considerably in the past 30 years due to changes in the environment that have been only partially identified. In this Series paper, we critically discuss candidate triggers of islet autoimmunity and factors thought to promote progression from autoimmunity to overt type 1 diabetes. We revisit previously proposed hypotheses to explain the growth in the incidence of type 1 diabetes in light of current data. Finally, we suggest a unified model in which immune tolerance to β cells can be broken by several environmental exposures that induce generation of hybrid peptides acting as neoautoantigens. [ABSTRACT FROM AUTHOR]

In spite of modern techniques, the burden for patients with type 1 diabetes mellitus will not disappear, and type 1 diabetes will remain a life-threatening disease causing severe complications and increased mortality. We have to learn of ways to stop the destructive process, preserve residual insulin secretion or even improve the disease via β-cell regeneration. This will give a milder disease, a more stable metabolism, simpler treatment and perhaps even cure. Therapies based on single drugs have not shown sufficient efficacy; however, there are several treatments with encouraging efficacy and no apparent, or rather mild, adverse events. As the disease process is heterogeneous, treatments have to be chosen to fit relevant subgroups of patients, and step by step efficacy can possibly be improved by the use of combination therapies. Thus immunosuppressive therapies like anti-CD3 and anti-CD20 monoclonal antibodies might be combined with fusion proteins such as etanercept [tumor necrosis factor (TNF)-α inhibitor] and/or abatacept (CTLA4-Ig) early after onset to stop the destructive process, supported by β-cell protective agents. The effect may be prolonged by using autoantigen therapy [glutamate decarboxylase (GAD) proinsulin], and by adding agents facilitating β-cell regeneration [e.g. glucagon-like peptide-1 (GLP-1)] there should be a good chance to make the disease milder, perhaps leading to cure in some patients. [ABSTRACT FROM AUTHOR]

To determine the importance of Lactobacillus in shaping the human gut microbiome, the microbial composition of stools from 1,602 children between the ages of 0.3 months and 37.2 months was analyzed in a general population cohort in the All Babies in Southeast Sweden study. Lactobacillus colonized only 32% of the total pediatric population at an average relative abundance of 0.29%. Lactobacillus was age-dependent, decreasing in prevalence and relative abundance over time. The main determining factor for Lactobacillus colonization was whether the individual was actively breastfeeding. Following cessation of breastfeeding, Lactobacillus prevalence rapidly declined. However, within the actively breastfeeding cohort, 45.6% of the population remained uncolonized by Lactobacillus. The presence versus absence of Lactobacillus was determined to be human leukocyte antigen (HLA) dependent. Individuals with HLA DR15-DQ6.2 were 3.4 times more likely to be colonized by Lactobacillus than those without the haplotype, and those with HLA DR5-DQ7 were more likely to have zero Lactobacillus despite actively breastfeeding. These results suggest that HLA genetics should be considered when designing Lactobacillus-based probiotics. [ABSTRACT FROM AUTHOR]

The article discusses findings of a study which examines the effectiveness of intralymphatic injection of autoantigens as effective interventions for patients with type 1 diabetes. The study explores the efficiency of GAD65 antigens to T cells in lymph nodes with oral vitamin D therapy for patients with type 1 diabetes. The study also reveals the positive results of type 1 diabetics after undergoing the immune intervention.

An essay is presented on professor of paediatrics Yngve Larsson. Topics discussed include creation of diabetes team such as dietician and diabetes nurse in Linkoping, Sweden for treatment of diabetes mellitus in children and adolescents; juvenile diabetes mellitus prognosis revealing poor prognosis of the disease in the early 1960s and importance of active insulin treatment through Linkoping Complication Study.

Abstract: In several diseases where the immune system plays an important role there has been a tremendous progress in treatment efficacy during the last decades. Based on necessary basic science these improvements are results of rapid, numerous and open-minded clinical trials where pieces of positive results step by step have been added into treatment schemes. Treatment of Type 1 diabetes has certainly improved but too slowly. It has been difficult to convince the scientific community of opinions which among non-professionals have been regarded as common sense such as the value of normal blood glucose and preservation of insulin secretion. Lack of motivation to participate in clinical trials has slowed down progress, as well as too narrow views on both pathogenesis of Type 1 diabetes and how studies should be designed to test therapeutic interventions. Studies in experimental animals can create and support hypothesis for human conditions but must not delay clinical trials too long. There is already evidence enough for intervention trials where immune suppression is combined with antigen treatment, beta cell protection, anti-inflammatory treatment, and efforts to stimulate beta cell regeneration. Regimens should be elaborated and first tried in those groups of patients where response can be expected to be best, and thereafter adjusted to increase efficacy step-wise, and in broader patient categories. [Copyright &y& Elsevier]

Background The infant microbiota may play a pathogenic role in coeliac disease (CD). Antibiotic treatment in pregnancy is common and could significantly impact the infant microbiota. In this study, we aimed to investigate the association between antibiotic exposure during pregnancy and CD in offspring. Methods Prospective questionnaire data on antibiotic exposure in pregnancy were available in 8729 children participating in the All Babies in Southeast Sweden (ABIS) cohort study, and of these 46 developed CD until December 2006. Cox regression estimated hazard ratios (HRs) for CD in the offspring among mothers exposed to antibiotics during pregnancy, with adjustment for parent-reported diary data on breastfeeding, age at gluten introduction and number of infections in the child's first year of life. Results Of the 1836 children exposed to antibiotics during pregnancy, 12 (0.7%) children developed CD as compared with 34/6893 (0.5%) unexposed children (HR = 1.33; 95%CI = 0.69-2.56). Risk estimates remained unchanged after adjustment for breastfeeding, age at gluten introduction and infection load in the child's first year of life (HR = 1.28; 95%CI = 0.66- 2.48). Conclusions We found no statistically significant association between antibiotic exposure during pregnancy and CD in offspring. This lack of association may either be true or the result of limited statistical power. [ABSTRACT FROM AUTHOR]

Aims/Hypothesis: Islet amyloid polypeptide (IAPP) is a beta cell hormone secreted together with insulin upon glucose stimulation. IAPP participates in normal glucose regulation, but IAPP is also known for its ability to misfold and form islet amyloid. Amyloid fibrils form through smaller cell toxic intermediates and deposited amyloid disrupts normal islet architecture. Even though IAPP and amyloid formation are much discussed in type 2 diabetes, our aim was to study the significance of IAPP in type 1 diabetes. Results: Plasma IAPP levels in children and adolescents with newly diagnosed type 1 diabetes (n = 224) were analysed and concentrations exceeding 100 pmol/L (127.2 – 888.7 pmol/L) were found in 11% (25/224). The IAPP increase did not correlate with C-peptide levels. Conclusions/Interpretation: Plasma levels of IAPP and insulin deviate in a subpopulation of young with newly-diagnosed type 1 diabetes. The determined elevated levels of IAPP might increase the risk for IAPP misfolding and formation of cell toxic amyloid in beta cells. This finding add IAPP-aggregation to the list over putative pathological factors causing type 1 diabetes. [ABSTRACT FROM AUTHOR]

Type one diabetes (T1D) seems a well-defined disease, but its classification may be difficult. Evidence is weak that an autoimmune process with insulitis causes loss of the beta cells in all patients. Some scientists propose that it may be caused by a virus, increased hygiene or the early introduction of cow's milk or gluten, while views about the nerve supply, vascular function and the beta cells own role tend to be disregarded. Immune interventions have had limited success. There are differences, but also similarities, between T1D and type 2 diabetes (T2D). Conclusion Several views on T1D have become so widely accepted that they may actually hamper progress into the true cause of this disease. Research on T1D needs to be carried out with an open mind, and clinicians might be wise to recommend a lifestyle that aims to decrease both the risk of T1D and T2D. [ABSTRACT FROM AUTHOR]

Keywords: COVID19; Type 1 diabetes; children; HbA1c; telemedicine EN COVID19 Type 1 diabetes children HbA1c telemedicine 933 934 2 02/19/21 20210301 NES 210301 Children tend to get very mild symptoms of COVID19 and rarely get severely ill,1 and COVID19 has no specific influence on diabetes other than any other infection.2 However, Covid19 may delay diagnosis, and lock-down of society can lead to that patients with diabetes do not get ordinary care causing poor metabolic control with increasing risks for complications3,4 and excess mortality.5 Sweden has, as the only country, chosen a policy with recommended isolation of the most vulnerable populations, but otherwise a rather open society. So far HbA1c has not increased but remained comparatively low with about 2/3 of the patients with HbA1c < 57 mmol/L (=6.5%) and only ca 6% of the patients with HbA1c > 70 mmol/L, a level which seems to be rather common in several other countries.10 To use telemedicine as the only alternative will probably not be good enough in the long run, especially not for patients with psychological problems and less stable family situation. COVID19, Type 1 diabetes, children, HbA1c, telemedicine. [Extracted from the article]

Abstract: Type 1 diabetes (T1D) patients have numeral and functional defects in peripheral immune cells, but the pre-diabetic period is fairly uncharacterized. Our aim was to analyze expression of immunological markers in T1D high risk children and relate it to clinical/immunological parameters. Children from ABIS (All Babies in Southeast Sweden) with ≥2 diabetes related autoantibodies were considered at high risk. Age-matched controls and new-onset T1D patients were included. Expression of genes related to immune cell function and different arms of the immune system was assessed in peripheral blood mononuclear cells using PCR array. Risk children had lower TNF and CD45, and although there were few differences between the groups, expression of many genes differed when comparing children with regard to residual insulin secretion. Hence, expression of immune related genes seemed related not only to the autoimmune process but rather to residual β-cell function, which was decreased already during the pre-diabetic phase. [Copyright &y& Elsevier]

Aims/hypothesis: We studied the decline of C-peptide during the first year after diagnosis of Type 1 diabetes (T1D), and its relation to various factors.Methods: 3824/4017 newly diagnosed patients (95%) were classified as T1D in a national study. In a non-selected subgroup of 1669 T1D patients we determined non-fasting C-peptide both at diagnosis and after 1 year, and analyzed decline in relation to clinical symptoms and signs, initial C-peptide and occurrence of auto-antibodies.Results: Younger children lost more C-peptide (p<0.001) and the higher the C-peptide at diagnosis the larger the decline during the first year (p<0.0000). Patients with higher BMI had higher C-peptide at diagnosis but lost more (p<0.01), and those with lower HbA1c, without symptoms and signs at diagnosis, and with higher BMI, had higher C-peptide at diagnosis, but lost more during the first year (p<0.001). Finally, patients diagnosed during autumn had higher C-peptide at diagnosis, but lost more during the coming year (p<0.001). Occurrence of auto-antibodies did not correlate with C-peptide decline, except possibly for a more rapid loss in IAA-positive patients.Conclusions/interpretation: Even in a restricted geographical area and narrow age range (<18 years), the natural course of Type 1 diabetes is heterogeneous. This should be considered in clinical trials. [ABSTRACT FROM AUTHOR]

Abstract: Aims: This study investigated whether psychological stress in the family during the child's first year of life are associated with the risk of childhood type 1 diabetes (T1D). According to the beta-cell stress hypothesis all factors that increase the need for, or the resistance to, insulin may be regarded as risk factors for T1D. Methods: Among 8921 children from the general population with questionnaire data from one parent at child's birth and at 1 year of age, 42 cases of T1D were identified up to 11–13 years of age. Additionally 15 cases with multiple diabetes-related autoantibodies were detected in a sub-sample of 2649 children. Results: Cox regression analyses showed no significant associations between serious life events (hazard ratio 0.7 for yes vs. no [95% CI 0.2–1.9], p =0.47), parenting stress (0.9 per scale score [0.5–1.7], p =0.79), or parental dissatisfaction (0.6 per scale score [0.3–1.2], p =0.13) during the first year of life and later diagnosis of T1D, after controlling for socioeconomic, demographic, and diabetes-related factors. Inclusion of children with multiple autoantibodies did not alter the results. Conclusions: No association between psychological stress early in life and development of T1D could be confirmed. [Copyright &y& Elsevier]

Abstract: Aims/hypothesis: We studied the decline of C-peptide during the first year after diagnosis of Type 1 diabetes (T1D), and its relation to various factors. Methods: 3824/4017 newly diagnosed patients (95%) were classified as T1D in a national study. In a non-selected subgroup of 1669 T1D patients we determined non-fasting C-peptide both at diagnosis and after 1 year, and analyzed decline in relation to clinical symptoms and signs, initial C-peptide and occurrence of auto-antibodies. Results: Younger children lost more C-peptide (p <0.001) and the higher the C-peptide at diagnosis the larger the decline during the first year (p <0.0000). Patients with higher BMI had higher C-peptide at diagnosis but lost more (p <0.01), and those with lower HbA1c, without symptoms and signs at diagnosis, and with higher BMI, had higher C-peptide at diagnosis, but lost more during the first year (p <0.001). Finally, patients diagnosed during autumn had higher C-peptide at diagnosis, but lost more during the coming year (p <0.001). Occurrence of auto-antibodies did not correlate with C-peptide decline, except possibly for a more rapid loss in IAA-positive patients. Conclusions/interpretation: Even in a restricted geographical area and narrow age range (<18 years), the natural course of Type 1 diabetes is heterogeneous. This should be considered in clinical trials. [Copyright &y& Elsevier]

Background: The 65-kD isoform of glutamic acid decarboxylase (GAD65) is a major autoantigen in type 1 diabetes. We hypothesized that alum-formulated GAD65 (GAD-alum) can preserve beta-cell function in patients with recent-onset type 1 diabetes. Methods: We studied 334 patients, 10 to 20 years of age, with type 1 diabetes, fasting C-peptide levels of more than 0.3 ng per milliliter (0.1 nmol per liter), and detectable serum GAD65 autoantibodies. Within 3 months after diagnosis, patients were randomly assigned to receive one of three study treatments: four doses of GAD-alum, two doses of GAD-alum followed by two doses of placebo, or four doses of placebo. The primary outcome was the change in the stimulated serum C-peptide level (after a mixed-meal tolerance test) between the baseline visit and the 15-month visit. Secondary outcomes included the glycated hemoglobin level, mean daily insulin dose, rate of hypoglycemia, and fasting and maximum stimulated C-peptide levels. Results: The stimulated C-peptide level declined to a similar degree in all study groups, and the primary outcome at 15 months did not differ significantly between the combined active-drug groups and the placebo group (P=0.10). The use of GAD-alum as compared with placebo did not affect the insulin dose, glycated hemoglobin level, or hypoglycemia rate. Adverse events were infrequent and mild in the three groups, with no significant differences. Conclusions: Treatment with GAD-alum did not significantly reduce the loss of stimulated C peptide or improve clinical outcomes over a 15-month period. (Funded by Diamyd Medical and the Swedish Child Diabetes Foundation; ClinicalTrials.gov number, NCT00723411.) [ABSTRACT FROM PUBLISHER]

Objective. To study T-helper (Th)1--Th2--Th3 gene activation profile in the small intestine and peripheral blood of children with celiac disease (CD) with special interest in the response to the gluten-free diet (GFD) treatment in order to elucidate an immune dysregulation not triggered by gluten. Material and methods. Small intestinal biopsies and venous blood were taken from seven children with CD (mean age: 8 years, four girls) at presentation and after 1 year of strict GFD. The Th1--Th2--Th3 gene expression profile was examined by real-time PCR arrays. The findings were compared with the corresponding expressions in peripheral blood and small intestinal biopsies from six reference children without CD (mean age: 6 years, four girls). Results. The Th1 gene expression profile including interferon (IFN)-γγ, signal transducer and activator of transcription (STAT) 1 and interferon regulatory factor (IRF) 1 together with reduced interleukin (IL)-2 expression was pronounced in small intestinal biopsies from children with untreated CD. A downregulation of IFN-γγ transcripts was seen after 1 year of GFD, but there was still increased expression of STAT1 and IRF1 in association with low IL-2 expression in spite of eliminated exposure to wheat gluten. By contrast, the decreased intestinal expression of Th2 gene markers observed at presentation was normalized with GFD. The alterations in the mucosal gene expression profile were not reflected in peripheral blood. Conclusion. The GFD did not correct the increased activation of the IFN-γγ signaling pathway related markers and reduced IL-2 expression, suggesting that they represent an immune dysregulation not dependent on gluten exposure. [ABSTRACT FROM AUTHOR]

Brekke HK, Ludvigsson J. Daily vegetable intake during pregnancy negatively associated to islet autoimmunity in the offspring—The ABIS study. Objective: To investigate if maternal diet during pregnancy is associated with occurrence of islet autoimmunity (IA) in the offspring. Methods: Of 21 700 infants invited to the All Babies in South-east Sweden (ABIS) study, 16 004 screening questionnaires, including a 22-item food frequency questionnaire (FFQ) regarding the mothers' diet during pregnancy, were completed after delivery. Follow-up of the children (questionnaires and blood sampling) was performed at 1, 2.5 and 5 yr of age. IA was defined as being positive (above the 95th percentile for healthy children) in two or more measurements of autoantibodies [glutamic acid decarboxylase (GADA); tyrosine phosphatase (IA-2A), insulin autoantibodies (IAA)] analysed at the three time points or being diagnosed with type 1 diabetes during the 5-yr follow-up period. The 5 724 children in whom we carried out two to three possible blood samplings were included in the study. Logistic regression analysis was used to identify variables predicting IA. Results: Of 5 724 children,191 (3.3%) were considered positive for IA. In a univariate analysis, less than daily consumption of vegetables (3–5 times/week) in the mothers' diet was associated with increased risk of IA (OR 1.71, 95% CI:1.24–2.35, p = 0.001) compared to daily consumption (p for trend = 0.004). The association was strengthened when adjusting for known IA-risk factors (p for trend <0.001). Conclusions: Daily consumption of vegetables in the mothers' diet during pregnancy was associated with a decreased risk of IA in the offspring. [ABSTRACT FROM AUTHOR]

This study aimed to analyse the impact of the disease and treatment on health-related quality of life (HRQOL) in intensively treated young patients with diabetes. Our main hypothesis was that metabolic control, gender, age and socio-economic status predict HRQOL. All children and adolescents (n = 400, 191 girls) and parents in a geographic population of two paediatric clinics in Sweden [mean age 13.2 yr, ±SD 3.9, range 2.6–19.6; mean duration of diabetes 5.1 yr, ±SD 3.8, range 0.3–17.6; yr mean haemoglobin A1c (HbA1c) 7.1%, ±SD 1.2, range 4.0–10.7] received the DISABKIDS questionnaire, a validated combined chronic generic and condition-specific HRQOL measure for children, and the EuroQol-5D questionnaire. Parents as proxy perceived HRQOL lower than their children. Adolescents with separated parents reported lower generic HRQOL (GeHRQOL) and diabetes-specific HRQOL (DiHRQOL) than those with parents living together (p = 0.027 and p = 0.043, respectively). Adolescent girls reported lower GeHRQOL (p = 0.041) and DiHRQOL (p = 0.001) than boys did. Parents of girls <8 yr of age reported lower DiHRQOL (p = 0.047) than did parents of boys <8 yr. In addition, a difference was found in HRQOL between centres. Intensive insulin therapy did not seem to lower HRQOL. If anything, along with better metabolic control, it increased HRQOL. A correlation between DiHRQOL and HbA1c was found in adolescents (r = −0.16, p = 0.046) and boys aged 8–12 yr (r = −0.28, p = 0.045). We conclude that the diabetes team can influence the HRQOL of the patients as there was a centre difference and because HRQOL is influenced by glycaemic control and insulin regimen. Girls seem to need extra support. [ABSTRACT FROM AUTHOR]

The article presents a trial which assessed the ability of alum-formulated glutamic acid decarboxylase (GAD) to reverse recent-onset type 1 diabetes in patients 10 to 18 years of age. Patients with type 1 diabetes with fasting C-peptide levels above 0.1 nmol per liter and GAD autoantibodies were randomly assigned to receive subcutaneous injections of 20 µg of GAD-alum or placebo on days 1 and 30 of the study. A mixed-meal tolerance test was performed on the patients to stimulate residual insulin secretion. This was measured as the C-peptide level. The immune system response to GAD-alum was studied. It was found that GAD-alum did not change the insulin requirement in patients with recent-onset type 1 diabetes, but may contribute to the preservation of residual insulin secretion.

Objective: The accelerator/beta-cell stress hypothesis regards insulin resistance as one common basis for type 1 and type 2 diabetes and weight increase as an important trigger of type 1 diabetes. To test this hypothesis, we examined children’s height and weight gain from birth to the time of diagnosis of type 1 diabetes. Method: Growth charts (n = 316) from children 0–16 yr old up to the time of diagnosis of type 1 diabetes were compared with growth charts from age- and sex-matched controls. Results: Compared with their controls, children who developed diabetes had experienced more pronounced gain in both weight and height. In the year of diagnosis, they were taller [0.5 vs. 0.36 standard deviation score (SDS), p < 0.03] and heavier (0.7 vs. 0.45 SDS, p < 0.01). Children who developed diabetes aged 5 yr or less gained more weight during the period between their third month and third year of life (p < 0.01). Children who were diagnosed between 6 and 10 yr of age had gained more in height before they were 5 yr old (p < 0.05). Regression analysis showed that a high weight or a high body mass index (BMI) at 5 yr of age indicated, more than the other measurements, a high risk for diabetes later during childhood, while height and weight at ages less than 5 yr did not add any further information on diabetes risk. Conclusions: Rapid growth before 7 yr of age and increased BMI in childhood are risk factors for later type 1 diabetes. These findings support the accelerator/beta-cell stress hypothesis. [ABSTRACT FROM AUTHOR]

Aim: To analyse the importance of mothers' smoking during pregnancy and/or environmental tobacco smoke (ETS) exposure in early childhood for children's health and well-being at the age of 3 years. Methods: Four groups from a population based cohort (n = 8850) were compared: children with nonsmoking mother during pregnancy and nonsmoking parents at the age of 3 years (n = 7091); children with only foetal exposure (n = 149); children exposed only postnatally (n = 895) and children exposed both pre- and postnatally (n = 595). Odds ratios and 95% confidence intervals were calculated. Results: Children exposed both pre- and postnatally had more wheezing (1.14; 1.07–1.21) and rhinitis (1.16; 1.06–1.26), used more cough-mixture (1.07; 1.01–1.14) and broncodilatating drugs (1.08; 1.02–1.15) and suffered more from excessive crying (1.31; 1.13–1.51) and irritability (1.27; 1.09–1.48) compared to children with nonsmoking parents. Children exposed only postnatally had more rhinitis (1.24; 1.12–1.37), used more cough-mixture (1.14; 1.05–1.29) and suffered more from poor sleep (1.26; 1.07–1.47) than children of nonsmoking parents. Children with prenatal exposure only used more broncodilatating drugs (1.45; 1.03–2.04) and suffered more from poor sleep (2.06; 1.09–3.87). Conclusion: Health differences, small but significant, indicate that prenatal and/or postnatal ETS exposure alone, or in combination, seems to interfere with child health, supporting the importance of zero tolerance. However, as most smoking parents in Sweden try to protect their children from ETS exposure, the results also might indicate that protective measures are worthwhile. [ABSTRACT FROM AUTHOR]

Aim: To explore the secular trends (time change) of pedometer-determined physical activity (steps per day) in Swedish schoolchildren 7–9 years of age from 2000 to 2006. It was an additional aim to examine the secular trends in body mass index. Methods: The study was analyzed between two cross-sectional cohorts on children 7–9 years of age carried out in October 2000 (336 children, 153 girls) and March/April 2006 (168 children, 83 girls) in the same five schools in south eastern Sweden, using identical procedures at the two occasions. Data of mean steps per day were collected during four consecutive weekdays (sealed pedometer Yamax SW-200 Tokyo, Japan) and in addition height and weight were measured. Results: Physical activity (mean steps per day) was significantly higher in 2006 than in 2000 among girls (13788 vs. 15141 steps per day) and boys (15991 vs. 16973 steps per day). The share of girls and boys to meet the preliminary weight control recommendations of 12000 and 15000 steps per day respectively was higher in 2006 than in 2000: 90% versus 75% (girls) and 67% versus 60% (boys). Conclusion: The level of physical activity (steps per day) during school weekdays was higher in 2006 than in 2000. Enhanced focus on physical activity in society and at school might have influenced the result. [ABSTRACT FROM AUTHOR]

Aim: To investigate whether a modern lifestyle, with a high-energy intake and a low level of physical activity, influences fasting plasma glucose concentration in healthy children. Methods: As a part of the prospective study ‘All Babies in Southeast Sweden’, 127 children from six preschool units chose to participate. The children, 56% girls and 44% boys, were 5–7 years old. Parents answered a questionnaire about their children's heredity, and physical exercise and eating habits. In the morning, before the children ate breakfast, fasting plasma glucose levels and weight, height and waist circumference were measured. Results: Fasting plasma glucose levels varied between 3.7 and 6.1 mmol/L, with both mean and median values of 4.7 mmol/L. There was no association between fasting plasma glucose level and body mass index (BMI), eating habits or degree of physical exercise. BMI and waist circumference were significantly correlated (p < 0.01). Children who play outdoors most frequently had a significantly lower BMI (p < 0.05) and waist circumference (p < 0.01), whereas children who more often watch TV had a significantly higher BMI (p < 0.01). Conclusion: A modern lifestyle, with low levels of exercise and high-energy consumption, may explain the increasing weight and even obesity of otherwise healthy, preschool children, but does not influence their fasting plasma glucose levels. [ABSTRACT FROM AUTHOR]

Supplementation with vitamin D during infancy, as well as intake of vitamin D during pregnancy, has been associated with decreased risk of type 1 diabetes or diabetes-related autoantibodies in children. The primary aim of this report was to investigate whether vitamin D supplementation during infancy is associated with diabetes-related autoimmunity at 1 and 2.5 yr in the children. Second, we examined whether consumption of vitamin-D-containing supplements during pregnancy is related to risk of autoimmunity in the offspring. Screening questionnaires were completed for 16 070 infants after delivery, including a food-frequency questionnaire regarding the mother’s use of dietary supplements during pregnancy. Parents of 11 081 and 8805 infants completed a follow-up questionnaire regarding the use of vitamin supplementation at 1 and 2.5 yr, respectively. Autoantibodies against glutamic acid decarboxylase and islet antigen-2 (IA-2) were analyzed in whole blood from 8694 children at 1 yr and 7766 children at 2.5 yr. Supplementation with AD-drops was not associated with autoantibodies at 1 or 2.5 yr. Use of vitamin-D-containing supplements during pregnancy was associated with reduced diabetes-related autoimmunity at 1 yr (adjusted odds ratio: 0.707, confidence interval: 0.520–0.962, p = 0.028) but not at 2.5 yr. In conclusion, no association was found between an intermediate dose of vitamin D supplementation during infancy and development of diabetes-related autoantibodies at 1 and 2.5 yr. Use of vitamin-D-containing supplements during pregnancy was associated with reduced development of glutamic acid decarboxylase autoantibodies or IA-2A in the offspring at 1 yr, but not at 2.5 yr. [ABSTRACT FROM AUTHOR]

These findings prompted comprehensive studies that aimed to prevent type 1 diabetes by giving babies formula that contained hydrolysed cows' milk rather than untreated cows' milk when their mothers were no longer breastfeeding. Sadly, the findings of that study produced dramatic headlines and speculation that skimmed milk powder could be one of the reasons behind the high incidence of type 1 diabetes among Swedish children. [Extracted from the article]

OBJECTIVE -- Earlier studies suggest that children with type 1 diabetes are more likely to have a subsequent diagnosis of celiac disease. However, research is sparse on the risk of subsequent type 1 diabetes in individuals with celiac disease. We sought to determine the risk of subsequent type 1 diabetes diagnosed before the age of 20 years in children and adolescents with celiac disease in a national, general population-based cohort. RESEARCH DESIGN AND METHODS -- We identified 9,243 children with a diagnosis of celiac disease in the Swedish national inpatient register between 1964 and 2003. We then identified five reference individuals matched at time of diagnosis for age, calendar year, sex, and county (n = 45,680). Only individuals with >1 year of follow-up after study entry (diagnosis of celiac disease) were included in the analyses. RESULTS -- Celiac disease was associated with a statistically significantly increased risk of subsequent type 1 diabetes before age 20 years (hazard ratio 2.4 [95% CI 1.9-3.0], P < 0.001). This risk increase was seen regardless of whether celiac disease was first diagnosed between 0 and 2 (2.2 [1.7-2.9], P < 0.001) or 3 and 20 (3.4 [1.9-6.1], P < 0.001) years of age. Individuals with prior celiac disease were also at increased risk of ketoacidosis or diabetic coma before the age of 20 years (2.3 [1.4-3.9], P = 0.001). CONCLUSIONS -- Children with celiac disease are at increased risk of subsequent type 1 diabetes. This risk increase is low considering that 95% of individuals with celiac disease are HLA-DQ2 positive. [ABSTRACT FROM AUTHOR]

There is a wide spectrum within the diabetes syndrome. Type 1 diabetes may have a slow progression with good residual insulin secretion and without autoantibodies, while phenotypic type 2 diabetes may have autoantibodies. A single patient may have traits of both types of diabetes. Their incidence increases in parallel. The etiology is mainly unknown, but environmental factors play an important role in genetically predisposed individuals. The search for just one single cause of manifest diabetes may be confusing. Different mechanism may be important in different parts of the world. Furthermore, certain mechanisms may lead to islet inflammation while other/additional mechanisms may increase insulin demand and cause insulin deficiency with manifestation of clinical diabetes. Several hypothesis of etiology may fit different parts of the disease process. Thus, increased hygiene may contribute to an imbalance of the immune system, facilitating autoimmune reactions when virus infections, or proteins like cow's milk or gluten, provoke. Increased insulin demand because of rapid growth, or insulin resistance caused by stress, infections, puberty, etc., lead to β cell stress, antigen presentation and may cause both an autoimmune reaction in genetically predisposed individuals, and insulin deficiency leading to manifest diabetes in individuals who have lost β cell function. Vitamins may modulate the immune process, but we know too little to give vitamin substitution. However, we do know that low physical exercise, obesity, and stress, increases insulin demand resulting in insulin deficiency. Now we can therefore intervene to prevent the diabetic syndrome. [ABSTRACT FROM AUTHOR]

This review deals with the two most serious side effects encountered with insulin pump therapy, severe hypoglycemia and diabetic ketoacidosis (DKA). Although clinical follow-up studies reported decreased rates of severe hypoglycemia, randomized studies have not confirmed this, showing no difference between the pump and injection groups. Less-severe hypoglycemia (mild/moderate/symptomatic hypoglycemia) was found to be more common with pump use. Some patients have inadvertently dosed or overdosed while awake or during sleep, causing fatal outcome in rare cases. Population-based or retrospective clinical studies reported a low rate of DKA in pump users that was still a higher rate than those using injection therapy, at least in some countries. In research settings and for patients with good compliance and adequate family support, the risk of DKA seems lower; many short-term studies report no DKA at all, possibly due to the increased attention given to participants. The use of continuous subcutaneous insulin infusion (CSII) seems to decrease the risk in patients who had recurrent DKA before pump start. Most episodes of DKA occur early after pump start, suggesting a learning curve occurs in all new forms of treatment. Increased teaching and awareness programs are vital to prevent severe hypoglycemia and DKA in children and adolescents using insulin pumps. [ABSTRACT FROM AUTHOR]

Abstract: This study aimed to investigate perceived quality of diabetes care. A geographic population of 400 type 1 diabetes patients <20 years received the validated questionnaire quality of care from the patient''s perspective (QPP) including additional context-specific items. Primary endpoints were perceived reality of care by specific items and factors and their subjective importance, respectively. Relations to severe hypoglycemia, HbA1c, insulin dose, BMI, age, duration and sociodemographic factors were also studied. On average, a high perceived quality of care was reported from both parents and adolescents (response rate 285/400 (71%) and 155/237 (65%), respectively); highest regarding possibility to talk to nurse/doctor in privacy, respect, general atmosphere, continuity in patient–physician relationship and patient participation. Lower perceived reality with higher subjective importance was seen for information about results from medical examinations and treatments and information about self-care, access to care and waiting time. While parents’ and their adolescents’ mean ratings correlated well for reality r =0.95 (p <0.001) and importance r =0.53 (p =0.023), parents rated reality level higher (p =0.012) and importance even higher (p <0.001). The QPP instrument used with additional context-specific items can provide specific information to be used in quality of care development. In our setting, improvements are needed regarding patient information, access to care and waiting time. [Copyright &y& Elsevier]

Aim: To examine socio-economic factors, smoking, coffee consumption and exclusive breastfeeding duration.Methods: This study was part of a prospective cohort study of children born between 1 October 1997 and 1 October 1999 (the All Babies in Southeast Sweden (ABIS) study). Eleven socio-economic characteristics (parental employment, civil status, whether parents were born in Sweden, parental education, residence at birth and during child's first year, crowded living), maternal smoking, coffee consumption, infant sex, siblings, parental age, and maternal alcohol consumption during pregnancy were analysed using logistic regression and Cox's proportional hazards method. All data were obtained through questionnaires distributed at infant birth and at 1 y of age. Exclusive breastfeeding duration<4 mo and actual breastfeeding duration were our main outcome measures.Results: Out of 10205 infants, 2206 (21.6%) were exclusively breastfed for less than 4 mo ("short exclusive breastfeeding"; SEBF). Backward stepwise regression analysis identified the following risk factors for SEBF: maternal smoking (95% confidence interval for adjusted odds ratio, 95% CI AOR 2.00-2.82), low maternal education (95% CI AOR 1.45-2.19), maternal employment less than 3 mo during pregnancy (95% CI AOR 1.17-1.54), paternal ageConclusion: This study indicates that socio-economic factors and smoking may be of importance to the risk of breastfeeding exclusively for less than 4 mo, while coffee consumption is not. [ABSTRACT FROM AUTHOR]

Objective . In adults, smoking seems to give protection against coeliac disease (CD). But, only one study has thus far investigated the association between maternal smoking during pregnancy and risk of CD in offspring. However, that study did not adjust for duration of exclusive breastfeeding, or look at passive smoking after birth. Material and methods . The current study was part of a prospective cohort study of infants born between 1 October 1997 and 1 October 1999 (the ABIS study; All Babies in Southeast Sweden). Data on smoking and exclusive breastfeeding were obtained through questionnaires distributed at infant birth and at 1 year of age. Coeliac disease was confirmed through small-bowel biopsy. Subgroup analyses were carried out according to maternal body mass index. Results . Nine out of 53 (17%) children with CD as opposed to 1699 out of 15,344 (11.1%) non-coeliac children had mothers who had smoked during pregnancy ( p =0.172). Mothers who had smoked during pregnancy were hence not at increased risk of having a child with CD (OR=1.64; 95% CI OR=0.80-3.37). Adjusting for duration of exclusive breastfeeding and the sex of infants in some 9585 children with data on exclusive breastfeeding lowered the OR for CD in mothers who smoked (adjusted OR (AOR)=0.89; 95% CI AOR=0.27-2.93; p =0.843). Parents who smoked during the child's first year of life were not at increased risk of having an offspring with CD (OR=1.94; 95% CI AOR=0.69-5.47; p =0. 203). Conclusions . No association was found between CD and parental smoking habits during pregnancy or during the child's first year of life. However, further studies with larger numbers of coeliac children are needed. [ABSTRACT FROM AUTHOR]

An aberrant mitogen-induced polarization of peripheral blood T cells has been associated with type 1 diabetes (T1D). We studied, in T1D, type 1 and 2 cytokine-induced expression of the interleukin-12 receptorβ2 chain (IL-12Rβ2 chain), which plays a critical role in regulating T-cell polarization. Peripheral blood lymphocytes from children with newly diagnosed T1D (n = 10; mean age 10 years), from children with longstanding T1D (n = 8; mean age 12·9 years) and from healthy children (n = 15; mean age 11·5 years) were stimulated with phytohaemagglutinin (PHA) in a type 1 (IL-12 and anti-IL-4) or a type 2 (IL-4 and anti-IL-12) cytokine environment. Secretion of interferon-γ (IFN-γ), IL-5 and IL-13, as detected by enzyme-linked immunosorbent assay (ELISA), and expression of the IL-12Rβ2 chain on CD4 and CD8 cells by flow cytometry, were analysed. Children with newly diagnosed and longstanding T1D had lower expression levels of the IL-12Rβ2 chain on IL-12Rβ2 chain-positive CD4 T cells (for a type 1 or a type 2 cytokine environment:P = 0·01 andP = 0·002 orP = 0·02 andP = 0·01, respectively) and on IL-12Rβ2 chain-positive CD8 T cells (for a type 1 or a type 2 cytokine environment:P = 0·007 andP = 0·0007 orP = 0·003 andP = 0·01, respectively) when compared to healthy children. A decreased percentage of IL-12Rβ2 chain-expressing CD4 T cells (P = 0·07 andP = 0·03) and CD8 T cells (P = 0·004 andP = 0·01) and increased secretion of IL-13 (P = 0·006 andP = 0·04) in a type 1 cytokine environment was seen in both groups of patients. Peripheral blood T cells from patients with both newly diagnosed and longstanding T1D showed poor polarization towards type 1 cells. [ABSTRACT FROM AUTHOR]

ABSTRACT. Objective. To improve metabolic control and prevent complications, both acute and late, we need to adjust treatment on the basis of the blood glucose (BG) profile, as not even the most active BG self-monitoring gives sufficient information. Design. We have used Continuous Glucose Monitoring System (CGMS; Medtronic MiniMed, Northridge, CA) in a controlled crossover study including 27 diabetic patients aged 12.5 ± 3.3 (mean; standard deviation; range: 5-19) years. All patients were treated with intensive insulin therapy, 14 with multiple injections, and 13 with pumps. The patients were randomized into an open or blind study arm. Both arms wore the CGMS sensor for 3 days every 2 weeks. CGMS profiles were used in the open study arm to adjust insulin therapy at follow-up visits every 6 weeks. Both the patients and the diabetes team were masked to the CGMS profiles in the blinded arm, and insulin therapy adjustments were based solely on 7-point BG profiles performed by the patients. At 3 months the 2 study arms were crossed over. Results. Despite initial problems with a device new to both patients and the diabetes team, hemoglobin A[sub 1]C decreased significantly in the open arm (from 7.70%7.31%) but not in the blind arm (7.75%-7.65%). A total of 26/27 patients experienced daytime low subcutaneous glucose (<3.0 mmol/L; .8 episodes/day; duration 58 ± 29 minutes; 5.5% of total time), and 27/27 patients had at least 1 nocturnal episode of low subcutaneous glucose (.4 episodes/night; duration 132 ± 81 minutes; 10.1% of total time). Conclusions. Use of CGMS facilitated an improved treatment, and patients received new insight and increased motivation. In this study, we found CGMS to be a useful tool for education and improving metabolic control. Pediatrics 2003;111:933-938; type 1 diabetes, children, glucose sensing, Continuous Glucose Monitoring System, metabolic control, hypoglycemia, Dawn phenomenon, Somogyi phenomenon, rebound... [ABSTRACT FROM AUTHOR]

Evaluates the parents reaction to the screening test to predict early diabetes on babies in Sweden. Identification of individuals with a high risk of developing type 1 diabetes; Purpose of the 'All Babies in Southeast Sweden' project; Method used to gather the data.