The primary objective of this multicenter, multinational, epidemiological study is the identification of infectious agents, dietary factors, or other environmental exposures that are associated with increased risk of autoimmunity and type 1 diabetes mellitus (T1DM). Factors affecting specific phenotypic manifestations such as early age of onset or rate of progression or with protection from the development of T1DM will also be identified. The Environmental Determinants of Diabetes in the Young (TEDDY) is an observational cohort study in which newborns who are younger than 4 months and have high-risk human leukocyte antigen alleles in the general population or are first-degree relatives (FDRs) of patients affected with T1DM will be enrolled. Six clinical centers in the USA and Europe will screen 361,588 newborns, of which it is anticipated that 17,804 will be eligible for enrollment with just over 7,800 followed. Recruitment will occur over 5 yr, with children being followed to the age of 15 yr. Identification of such factors will lead to a better understanding of disease pathogenesis and result in new strategies to prevent, delay, or reverse T1DM.

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Maternal exposure to air pollution and type 1 diabetes -Accounting for genetic factors. Link to publication Citation for published version (APA): Malmqvist, E., Larsson, H., Jönsson, I., Rignell-Hydbom, A., Ivarsson, S., Tinnerberg, H., ... Rylander, L. (2015). Maternal exposure to air pollution and type 1 diabetes -Accounting for genetic factors. Environmental Research, 140, 268-274. DOI: 10.1016/j.envres.2015 General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal

Aims/hypothesis Children participating in longitudinal type 1 diabetes prediction studies were reported to have less severe disease at diabetes diagnosis. Our aim was to investigate children who from birth participated in the Diabetes Prediction in Skåne (DiPiS) study for metabolic status at diagnosis and then continued to be followed for two years of regular clinical care. Methods Children, followed in DiPiS before diagnosis, were compared to children in the same birth cohort who did not participate in follow-up. Metabolic status, symptoms at diagnosis as well as HbA1c and doses of insulin at 3, 6, 12 and 24 months after diagnosis were compared. Results Children, followed in DiPiS and diagnosed at 2–12 years of age, had 0.8% (9 mmol/mol) lower HbA1c at diagnosis than those who were not followed (p=0.006). At diagnosis, fewer DiPiS children had symptoms (p=0.014) and ketoacidosis at diagnosis were reduced (2% compared to 18%, p=0.005). During regular clinical care, HbA1c levels for the DiPiS children remained lower both at 12 (0.4% (4 mmol/mol); p=0.009) and 24 months (0.8% (9 mmol/mol) p <0.001) after diagnosis, despite no difference in total daily insulin between the two groups. Conclusions Participation in prospective follow-up before diagnosis of type 1 diabetes leads to earlier diagnosis with fewer symptoms, decreased incidence of ketoacidosis as well as better metabolic control up to two years after diagnosis. Our data indicate that metabolic control at the time of diabetes diagnosis is important for early metabolic control possibly affecting the risk of long-term complications.

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Gestational enterovirus (EV) infections have been associated with an increased risk for type 1 diabetes in the offspring. We therefore analyzed non-diabetic mothers for EV exposure in early pregnancy in relation to type 1 diabetes HLA-DQ risk genotypes and seroconversion to islet autoantibodies during pregnancy. Non-diabetic mothers who had islet autoantibodies (n = 365) against glutamic acid decarboxylase (GADA), islet antigen-2 autoantibodies (IA-2A), or insulin autoantibodies (IAA), in early pregnancy and at delivery were compared to islet autoantibody-negative mothers (n = 1457) matched for age and sampling date. Mothers were genotyped for HLA-DQ and analyzed for both EV-RNA and EV-IgM. EV-IgM, but not EV-RNA, was detected during early pregnancy in 12% of islet autoantibody-positive mothers compared to 11% of the controls. In early pregnancy, mothers with HLA-DQ 2/2 or 2/X genotypes showed an increased risk for islet autoantibodies at delivery (OR 1.85; p = 0.001). After adjusting for parity, maternal age, year of birth, and season of early pregnancy, early pregnancy EV-IgM combined with DQ2/2 or 2/X increased the risk for islet autoantibodies (OR 3.10; 95% CI 1; p = 0.008). EV-IgM in early pregnancy increased the risk for islet autoantibodies at delivery in non-diabetic mothers with HLA-DQ 2/2 or 2/X type 1 diabetes risk genotypes.

The effects of continuous and intermittent inhalation of trichloroethylene (TCE) were studied in male and female mice. Plasma butyrylcholinesterase (BuChE) activity, body, liver, kidney and spleen weights were measured. The liver was studied histologically and motor activity measured with doppler radar. Continuous TCE‐exposure (37–300 p.p.m.) increased plasma BuChE activity in the males in a time and concentration dependent manner. After 30 days at 37 p.p.m. the increase was about 25%. Exposure to 300 p.p.m. for 30 days increased the activity three times. BuChE activity in females was only slightly influenced even at 300 p.p.m. Liver weight was increased in a time and concentration dependent manner in both sexes. In animals continuously exposed for 30 days to 300 p.p.m., liver weight was roughly twice that of the air‐exposed controls. Morphological changes were observed in the liver of TCE‐exposed animals. Above 150 p.p.m. kidney weight in both sexes was significantly increased. This effect was more pronounced in the males than in the females. Spleen weight was not influenced by the exposure. Body weight increase was slightly lower in exposed animals. Plasma BuChE activity and liver weight returned to normal when exposure was terminated. Intermittent exposure to short pulses of high concentration of TCE had roughly the same effect on BuChE, body and organ weights as continuous exposure to the same time‐weighted average. Motor activity was affected by the intermittent exposure schedules. At 900 p.p.m. decrease in activity was observed. At 3600 p.p.m. motor activity was considerably increased.

Larsson & the DiPiS study Group (2018) Childhood thyroid autoimmunity and relation to islet autoantibodies in children at risk for type 1 diabetes in the diabetes prediction in