A surge in serum mucosal cytokines associated with seroconversion in children at risk for type 1 diabetes.

OnlinePublAims/Introduction: Autoantibodies to pancreatic islet antigens identify young children at high risk of type 1 diabetes. On a background of genetic susceptibility, islet autoimmunity is thought to be driven by environmental factors, of which enteric viruses are prime candidates. We sought evidence for enteric pathology in children genetically atrisk for type 1 diabetes followed from birth who had developed islet autoantibodies (“seroconverted”), by measuring mucosa-associated cytokines in their sera. Materials and Methods: Sera were collected 3 monthly from birth from children with a first-degree type 1 diabetes relative, in the Environmental Determinants of Islet Autoimmunity (ENDIA) study. Children who seroconverted were matched for sex, age, and sample availability with seronegative children. Luminex xMap technology was used to measure serum cytokines. Results: Of eight children who seroconverted, for whom serum samples were available at least 6 months before and after seroconversion, the serum concentrations of mucosaassociated cytokines IL-21, IL-22, IL-25, and IL-10, the Th17-related cytokines IL-17F and IL23, as well as IL-33, IFN-c, and IL-4, peaked from a low baseline in seven around the time of seroconversion and in one preceding seroconversion. These changes were not detected in eight sex- and age-matched seronegative controls, or in a separate cohort of 11 unmatched seronegative children. Conclusions: In a cohort of children at risk for type 1 diabetes followed from birth, a transient, systemic increase in mucosa-associated cytokines around the time of seroconversion lends support to the view that mucosal infection, e.g., by an enteric virus, may drive the development of islet autoimmunity.Leonard C Harrison, Esther Bandala-Sanchez, Helena Oakey, Peter G Colman, Kelly Watson, Ki Wook Kim, Roy Wu, Emma E Hamilton-Williams, Natalie L Stone, Aveni Haynes, Rebecca L Thomson, Peter J Vuillermin, Georgia Soldatos, William D Rawlinson, Kelly J McGorm, Grant Morahan, Simon C Barry, Richard O Sinnott, John M Wentworth, Jennifer J Couper, Megan AS Penno, on behalf of the ENDIA Study Grou

Women with type 1 diabetes exhibit a progressive increase in gut Saccharomyces cerevisiae in pregnancy associated with evidence of gut inflammation.

Aims: Studies of the gut microbiome have focused on its bacterial composition. We aimed to characterize the gut fungal microbiome (mycobiome) across pregnancy in women with and without type 1 diabetes. Methods: Faecal samples (n = 162) were collected from 70 pregnant women (45 with and 25 without type 1 diabetes) across all trimesters. Fungi were analysed by internal transcribed spacer 1 amplicon sequencing. Markers of intestinal inflammation (faecal calprotectin) and intestinal epithelial integrity (serum intestinal fatty acid binding protein; I-FABP), and serum antibodies to Saccharomyces cerevisiae (ASCA) were measured. Results: Women with type 1 diabetes had decreased fungal alpha diversity by the third trimester, associated with an increased abundance of Saccharomyces cerevisiae that was inversely related to the abundance of the anti-inflammatory butyrate-producing bacterium Faecalibacterium prausnitzii. Women with type 1 diabetes had higher concentrations of calprotectin, I-FABP and ASCA. Conclusions: Women with type 1 diabetes exhibit a shift in the gut mycobiome across pregnancy associated with evidence of gut inflammation and impaired intestinal barrier function. The relevance of these findings to the higher rate of pregnancy complications in type 1 diabetes warrants further study.Esther Bandala-Sanchez, Alexandra J. Roth-Schulze, Helena Oakey Megan A.S. Penno, Naiara G. Bediaga, Gaetano Naselli, Katrina M. Ngui, Alannah D. Smith, Dexing Huang, Enrique Zozaya-Valdes, Rebecca L. Thomson, James D. Brown, Peter J. Vuillermin, Simon C. Barry, Maria E. Craig, William D. Rawlinson, Elizabeth A. Davis, Mark Harris, Georgia Soldatos, Peter G. Colman, John M. Wentworth, Aveni Haynes, Grant Morahan, Richard O. Sinnott, Anthony T. Papenfuss, Jennifer J. Couper, Leonard C. Harrison, on behalf of the ENDIA Study Grou

Potential links between the emerging risk factors for food allergy and vitamin D status

A variety of hypotheses have been proposed to explain the recently described increase in food allergy among children living in developed countries. In this study, we summarize the emerging risk factors for IgE-mediated food allergy in early life, and then review the evidence for and against an association between low vitamin status (VDS) and food allergy. We consider whether each of the epidemiological variables that have been associated with food allergy may also be associated with VDS; and argue that future studies must adequately account for the potential relationships between risk factors for food allergy and VDS, and must also discriminate between vitamin D derived by sun exposure, diet and oral supplementation.<br /

Evaluation of protocol amendments to the Environmental Determinants of Islet Autoimmunity (ENDIA) study during the COVID-19 pandemic

LetterThe Environmental Determinants of Islet Autoimmunity (ENDIA) Study is an Australia-wide observational pregnancy-birth cohort of children at genetic risk on account of a first-degree relative with type 1 diabetes (1). 1511 participants were recruited from all Australian States and Territories from 2013-2019 with 1473 live-born infants in follow-up. The standard protocol involves 3-monthly face-to-face visits from pregnancy until the child is 2 years of age, then 6-monthly visits. Study staff across nine centres in five States collect biospecimens (blood, urine, stool, swabs) and administer lifestyle and dietary questionnaires. Approximately 10% of the cohort are engaged in a Regional Participant Program (2) that requires self-collection of sample types except for venepuncture performed at local pathology services.Megan A. S. Penno, Amanda J. Anderson, Rebecca L. Thomson, Kelly McGorm, Simon C. Barry, Peter G. Colman, Maria E. Craig, Elizabeth A. Davis, Mark Harris, Aveni Haynes, Grant Morahan, Helena Oakey, William D. Rawlinson, Richard O. Sinnott, Georgia Soldatos, Peter J. Vuillermin, John M. Wentworth, Leonard C. Harrison, Jennifer J. Couper, the ENDIA Study Grou

Mental Health During Late Pregnancy and Postpartum in Mothers With and Without Type 1 Diabetes: The ENDIA Study

This article contains supplementary material online at https://doi.org/10.2337/figshare.18551261.Objective: Pregnancy and type 1 diabetes are each associated with increased anxiety and depression, but the combined impact on well-being is unresolved. We compared the mental health of women with and without type 1 diabetes during pregnancy and postpartum and examined the relationship between mental health and glycemic control. Research Design and Methods: Participants were women enrolled from 2016 to 2020 in the Environmental Determinants of Islet Autoimmunity (ENDIA) study, a pregnancy to birth prospective cohort following children with a first-degree relative with type 1 diabetes. Edinburgh Postnatal Depression Scale (EPDS) and Perceived Stress Scale (PSS) were completed during the third trimester (T3) (median [interquartile range] 34 [32, 36] weeks) and postpartum (14 [13, 16] weeks) by 737 women (800 pregnancies) with (n = 518) and without (n = 282) type 1 diabetes. Results: EPDS and PSS scores did not differ between women with and without type 1 diabetes during T3 and postpartum. EPDS scores were marginally higher in T3: predicted mean (95% CI) 5.7 (5.4, 6.1) than postpartum: 5.3 (5.0, 5.6), independent of type 1 diabetes status (P = 0.01). HbA1c levels in type 1 diabetes were 6.3% [5.8, 6.9%] in T3 and did not correlate with EPDS or PSS scores. Reported use of psychotropic medications was similar in women with (n = 44 of 518 [8%]) and without type 1 diabetes (n = 17 of 282 [6%]), as was their amount of physical activity. Conclusions: Overall, mental health in late pregnancy and postpartum did not differ between women with and without type 1 diabetes, and mental health scores were not correlated with glycemic control.Madeleine Hall, Helena Oakey, Megan A.S. Penno, Kelly McGorm, Amanda J. Anderson, Pat Ashwood, Peter G. Colman, Maria E. Craig, Elizabeth A. Davis, Mark Harris, Leonard C. Harrison, Aveni Haynes, Claire Morbey, Richard O. Sinnott, Georgia Soldatos, Peter J. Vuillermin, John M. Wentworth, Rebecca L. Thomson, Jennifer J. Couper on behalf of the ENDIA Study Grou

Population-based plasma lipidomics reveals developmental changes in metabolism and signatures of obesity risk: a mother-offspring cohort study

10.1186/s12916-022-02432-yBMC Medicine20124