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Ludvigsson, Johnny, ProfessorORCID iD iconorcid.org/0000-0003-1695-5234
Alternative names
Publications (10 of 401) Show all publications
Taylor, P. N., Collins, K. S., Lam, A., Karpen, S. R., Greeno, B., Walker, F., . . . Dayan, C. M. (2023). C-peptide and metabolic outcomes in trials of disease modifying therapy in new-onset type 1 diabetes: an individual participant meta-analysis. The Lancet Diabetes and Endocrinology, 11(12), 915-925
Open this publication in new window or tab >>C-peptide and metabolic outcomes in trials of disease modifying therapy in new-onset type 1 diabetes: an individual participant meta-analysis
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2023 (English)In: The Lancet Diabetes and Endocrinology, ISSN 2213-8587, E-ISSN 2213-8595, Vol. 11, no 12, p. 915-925Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Elsevier, 2023
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:liu:diva-201566 (URN)10.1016/S2213-8587(23)00267-X (DOI)37931637 (PubMedID)
Available from: 2024-03-12 Created: 2024-03-12 Last updated: 2024-03-12
Wegmann, B., Tatemoto, P., Miemczyk, S., Ludvigsson, J. & Guerrero-Bosagna, C. (2023). Identification of potentially relevant metals for the etiology of autism by using a Bayesian multivariate approach for partially censored values. Scientific Reports, 13(1), Article ID 12622.
Open this publication in new window or tab >>Identification of potentially relevant metals for the etiology of autism by using a Bayesian multivariate approach for partially censored values
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2023 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 13, no 1, article id 12622Article in journal (Refereed) Published
Abstract [en]

Heavy metals are known to be able to cross the placental and blood brain barriers to affect critical neurodevelopmental processes in the fetus. We measured metal levels (Al, Cd, Hg, Li, Pb and Zn) in the cord blood of newborns and in the serum of the same children at 5 years of age, and compared between individuals with or without (controls) autism spectrum disorder (ASD) diagnosis. The samples were from a biobank associated with the All Babies in Southeast Sweden (ABIS) registry. We proposed a Bayesian multivariate log-normal model for partially censored values to identify potentially relevant metals for the etiology of ASD. Our results in cord blood suggest prenatal Al levels could be indicative of later ASD incidence, which could also be related to an increased possibility of a high, potentially toxic, exposure to Al and Li during pregnancy. In addition, a larger possibility of a high, potentially beneficial, exposure to Zn could occur during pregnancy in controls. Finally, we found decisive evidence for an average increase of Hg in 5-year-old ASD children compared to only weak evidence for controls. This is concordant with previous research showing an impaired ability for eliminating Hg in the ASD group.

Place, publisher, year, edition, pages
NATURE PORTFOLIO, 2023
National Category
Probability Theory and Statistics Biological Sciences
Identifiers
urn:nbn:se:liu:diva-197082 (URN)10.1038/s41598-023-38780-9 (DOI)001042854100016 ()37537167 (PubMedID)
Funder
Linköpings universitet
Note

Funding: Faculty of Arts and Sciences at Linkouml;ping University, Sweden; Escher Fund for Autism; Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning (FORMAS); Barndiabetesfonden (Swedish Child Diabetes Foundation); Swedish Council for Working Life and Social Research [FAS20041775, K2005-72X-11242-11A]; Swedish Research Council [K2008-69X-20826-01-4, K 98-99D-12813-01A]; Medical Research Council of Southeast Sweden (FORSS); JDRF Wallenberg Foundation [2018-01074]; OEstgoeta Brandstodsbolag; Region OEstergoetland; Linkoeping university, Sweden; Joanna Cocozza Foundation; Linkoeping University;  [FAS2004-1775]

Available from: 2023-08-22 Created: 2023-08-22 Last updated: 2023-09-26
Ludvigsson, J. (2023). Immune Interventions at Onset of Type 1 Diabetes — Finally, a Bit of Hope. New England Journal of Medicine, 389(23), 2199-2201
Open this publication in new window or tab >>Immune Interventions at Onset of Type 1 Diabetes — Finally, a Bit of Hope
2023 (English)In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 389, no 23, p. 2199-2201Article in journal, Editorial material (Other academic) Published
Place, publisher, year, edition, pages
Massachusetts Medical Society, 2023
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:liu:diva-200807 (URN)10.1056/nejme2312091 (DOI)001142895100006 ()38055258 (PubMedID)
Available from: 2024-02-08 Created: 2024-02-08 Last updated: 2024-02-23
Tojjar, J., Cervin, M., Hedlund, E., Brahimi, Q., Forsander, G., Elding Larsson, H., . . . Carlsson, A. (2023). Sex Differences in Age of Diagnosis, HLA Genotype, and Autoantibody Profile in Children With Type 1 Diabetes. Diabetes Care, 46(11), 1993-1996
Open this publication in new window or tab >>Sex Differences in Age of Diagnosis, HLA Genotype, and Autoantibody Profile in Children With Type 1 Diabetes
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2023 (English)In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 46, no 11, p. 1993-1996Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
American Diabetes Association, 2023
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:liu:diva-201569 (URN)10.2337/dc23-0124 (DOI)37699205 (PubMedID)
Funder
Swedish Child Diabetes Foundation
Available from: 2024-03-12 Created: 2024-03-12 Last updated: 2024-03-12
Berryman, M. A., Milletich, P. L., Petrone, J. R., Roesch, L. F., Ilonen, J., Triplett, E. W. & Ludvigsson, J. (2022). Autoimmune-associated genetics impact probiotic colonization of the infant gut. Journal of Autoimmunity, 133, Article ID 102943.
Open this publication in new window or tab >>Autoimmune-associated genetics impact probiotic colonization of the infant gut
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2022 (English)In: Journal of Autoimmunity, ISSN 0896-8411, E-ISSN 1095-9157, Vol. 133, article id 102943Article in journal (Refereed) Published
Abstract [en]

To exemplify autoimmune-associated genetic influence on the colonization of bacteria frequently used in probiotics, microbial composition of stool from 1326 one-year-old infants was analyzed in a prospective general-population cohort, All Babies In Southeast Sweden (ABIS). We show that an individual's HLA haplotype composition has a significant impact on which common Bifidobacterium strains thrive in colonizing the gut. The effect HLA has on the gut microbiome can be more clearly observed when considered in terms of allelic dosage. HLA DR1-DQ5 showed the most significant and most prominent effect on increased Bifidobacterium relative abundance. Therefore, HLA DR1-DQ5 is proposed to act as a protective haplotype in many individuals. Protection-associated HLA haplotypes are more likely to influence the promotion of specific bifidobacteria. In addition, strain-level differences are correlated with colonization proficiency in the gut depending on HLA haplotype makeup. These results demonstrate that HLA genetics should be considered when designing effective probiotics, particularly for those at high genetic risk for autoimmune diseases.

Place, publisher, year, edition, pages
Elsevier, 2022
Keywords
Autoimmune; Bifidobacterium; HLA; Human leukocyte antigen; Microbiome; Probiotics
National Category
Genetics Gastroenterology and Hepatology
Identifiers
urn:nbn:se:liu:diva-192441 (URN)10.1016/j.jaut.2022.102943 (DOI)000972485500002 ()36356550 (PubMedID)
Note

Funding: Barndiabetesfonden (Swedish Child Diabetes Foundation); Swedish Council for Working Life and Social Research [FAS2004-1775]; Swedish Research Council [K2005-72X-11242-11A, K2008-69X-20826-01-4]; Medical Research Council of Southeast Sweden (FORSS); JDRF Wallenberg Foundation [K 98-99D-12813-01A]; Ostg ota Brandstodsbolag; Region Osterg otland; Link oping university, Sweden; Joanna Cocozza Foundation; JDRF [1-INO-2018-637-A-N]

Available from: 2023-03-17 Created: 2023-03-17 Last updated: 2023-06-01
Bruzzaniti, S., Piemonte, E., Mozzillo, E., Bruzzese, D., Lepore, M. T., Carbone, F., . . . Galgani, M. (2022). High levels of blood circulating immune checkpoint molecules in children with new-onset type 1 diabetes are associated with the risk of developing an additional autoimmune disease. Diabetologia, 65, 1390-1397
Open this publication in new window or tab >>High levels of blood circulating immune checkpoint molecules in children with new-onset type 1 diabetes are associated with the risk of developing an additional autoimmune disease
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2022 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 65, p. 1390-1397Article in journal (Refereed) Published
Abstract [en]

Aims/hypothesis We assessed the levels of blood circulating immune checkpoint molecules (ICMs) at diagnosis of type 1 diabetes, and determined their association with the risk of developing an additional autoimmune disorder over time. Methods Children with new-onset type 1 diabetes (n = 143), without biological and/or clinical signs of additional autoimmune disorders, and healthy children (n = 75) were enrolled, and blood circulating levels of 14 ICMs were measured. The children with type 1 diabetes were divided into two groups on the basis of the development of an additional autoimmune disease in the 5 years after diabetes onset. Differences in soluble ICM levels between the groups were assessed, and a Cox regression analysis was used to evaluate their association with the risk of development of an additional autoimmune disease over time. To validate the data, circulating ICMs were measured in an independent cohort of 60 children with new-onset type 1 diabetes stratified into two groups. Results We found that the levels of circulating ICMs were significantly higher in children with new-onset diabetes compared with healthy children. Further, we observed that children with type 1 diabetes who developed a second autoimmune disease over time (T1D-AAD(+) children) had higher levels of soluble ICMs than children with type 1 diabetes who did not (T1D-AAD(-) children). Cox regression models revealed that high circulating levels of CD137/4-1BB and PD-1 molecules at diabetes diagnosis were associated with the risk of developing an additional autoimmune disease in both type 1 diabetes cohorts. Conclusions/interpretation Our findings suggest that soluble CD137/4-1BB and PD-1 molecules may be used as prognostic biomarkers in children with type 1 diabetes, and may pave the way for novel immunological screening at diabetes onset, allowing early identification of children at higher risk of developing other autoimmune conditions over time.

Place, publisher, year, edition, pages
SPRINGER, 2022
Keywords
Autoimmune diseases; Autoimmune thyroiditis; Biomarkers; Coeliac disease; Soluble immune-checkpoint molecules; Type 1 diabetes
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:liu:diva-185592 (URN)10.1007/s00125-022-05724-3 (DOI)000799731900002 ()35610521 (PubMedID)
Note

Funding Agencies|European Foundation for the Study of Diabetes/Novo Nordisk Programme for Diabetes Research in Europe; Fondazione Italiana Sclerosi Multipla [2020/R/13, 2016/R/10, 2018/R/4, 2016/R/18, 2018/S/5]; Progetti di Rilevante Interesse Nazionale [202077EYN7, 2017 K55HLC 001]; Ministero della Salute [GR-2016-023637259]; National Multiple Sclerosis Society [PP-1606-24687, RF-201912371111]

Available from: 2022-06-08 Created: 2022-06-08 Last updated: 2023-02-21Bibliographically approved
Spencer, N. J., Ludvigsson, J., You, Y., Francis, K., Abu Awad, Y., Markham, W., . . . McGrath, J. J. (2022). Household income and maternal education in early childhood and activity-limiting chronic health conditions in late childhood: findings from birth cohort studies from six countries. Journal of Epidemiology and Community Health, 76(11), 939-948
Open this publication in new window or tab >>Household income and maternal education in early childhood and activity-limiting chronic health conditions in late childhood: findings from birth cohort studies from six countries
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2022 (English)In: Journal of Epidemiology and Community Health, ISSN 0143-005X, E-ISSN 1470-2738, Vol. 76, no 11, p. 939-948Article in journal (Refereed) Published
Abstract [en]

Background We examined absolute and relative relationships between household income and maternal education during early childhood (&lt;5 years) with activity-limiting chronic health conditions (ALCHC) during later childhood in six longitudinal, prospective cohorts from high-income countries (UK, Australia, Canada, Sweden, Netherlands, USA). Methods Relative inequality (risk ratios, RR) and absolute inequality (Slope Index of Inequality) were estimated for ALCHC during later childhood by maternal education categories and household income quintiles in early childhood. Estimates were adjusted for mother ethnicity, maternal age at birth, child sex and multiple births, and were pooled using meta-regression. Results Pooled estimates, with over 42 000 children, demonstrated social gradients in ALCHC for high maternal education versus low (RR 1.54, 95% CI 1.28 to 1.85) and middle education (RR 1.24, 95% CI 1.11 to 1.38); as well as for high household income versus lowest (RR 1.90, 95% CI 1.66 to 2.18) and middle quintiles (RR 1.34, 95% CI 1.17 to 1.54). Absolute inequality showed decreasing ALCHC in all cohorts from low to high education (range: -2.85% Sweden, -13.36% Canada) and income (range: -1.8% Sweden, -19.35% Netherlands). Conclusion We found graded relative risk of ALCHC during later childhood by maternal education and household income during early childhood in all cohorts. Absolute differences in ALCHC were consistently observed between the highest and lowest maternal education and household income levels across cohort populations. Our results support a potential role for generous, universal financial and childcare policies for families during early childhood in reducing the prevalence of activity limiting chronic conditions in later childhood.

Place, publisher, year, edition, pages
BMJ PUBLISHING GROUP, 2022
Keywords
child health; health inequalities; life course epidemiology; cohort studies
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:liu:diva-187359 (URN)10.1136/jech-2022-219228 (DOI)000829471200001 ()35863874 (PubMedID)
Note

Funding Agencies|Canadian Institutes of Health Research [OCO-79897, MOP-89886, MSH-95353, ROG-110537]; County Council of Ostergotland; Swedish Research Council [K2005-72X-11242-11A, K2008-69X-20826-01-4]; Swedish Child Diabetes Foundation (Barndiabetesfonden); Juvenile Diabetes Research Foundation; Wallenberg Foundation [K 98-99D-12813-01A]; Medical Research Council of Southeast Sweden(FORSS); Swedish Council for Working Life and Social Research [FAS2004-1775]; Ostgota Brandstodsbolag; Australian Government Department of Social Services; partner organisations Australian Institute of Family Studies (AIFS); Australian Bureau of Statistics (ABS); Erasmus Medical Center, Rotterdam; Erasmus University Rotterdam; Netherlands Organisation for Health Research and Development (ZonMw); Netherlands Organisation for Scientific Research (NWO); Ministry of Health, Welfare and Sport; Ministry of Youth and Families; Human Resources and Skills Development Canada (HRSDC); Social Sciences and Humanities Research Council (SSHRC); Canadian Institute for Health Research (CIHR); Canadian Foundation for Innovation (CFI); Statistics Canada; Economic and Social Research Council; Office of National Statistics; various government departments; US Bureau of Labor Statistics; National Institute for Child Health and Human Development; [907.00303]; [916.10159]

Available from: 2022-08-19 Created: 2022-08-19 Last updated: 2023-02-24Bibliographically approved
Andersson White, P., Abu Awad, Y., Gauvin, L., Spencer, N. J., McGrath, J. J., Clifford, S. A., . . . Faresjö, T. (2022). Household income and maternal education in early childhood and risk of overweight and obesity in late childhood: Findings from seven birth cohort studies in six high-income countries. International Journal of Obesity, 46, 1703-1711
Open this publication in new window or tab >>Household income and maternal education in early childhood and risk of overweight and obesity in late childhood: Findings from seven birth cohort studies in six high-income countries
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2022 (English)In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 46, p. 1703-1711Article in journal (Refereed) Published
Abstract [en]

Background/objectives This study analysed the relationship between early childhood socioeconomic status (SES) measured by maternal education and household income and the subsequent development of childhood overweight and obesity. Subjects/methods Data from seven population-representative prospective child cohorts in six high-income countries: United Kingdom, Australia, the Netherlands, Canada (one national cohort and one from the province of Quebec), USA, Sweden. Children were included at birth or within the first 2 years of life. Pooled estimates relate to a total of N = 26,565 included children. Overweight and obesity were defined using International Obesity Task Force (IOTF) cut-offs and measured in late childhood (8-11 years). Risk ratios (RRs) and pooled risk estimates were adjusted for potential confounders (maternal age, ethnicity, child sex). Slope Indexes of Inequality (SII) were estimated to quantify absolute inequality for maternal education and household income. Results Prevalence ranged from 15.0% overweight and 2.4% obese in the Swedish cohort to 37.6% overweight and 15.8% obese in the US cohort. Overall, across cohorts, social gradients were observed for risk of obesity for both low maternal education (pooled RR: 2.99, 95% CI: 2.07, 4.31) and low household income (pooled RR: 2.69, 95% CI: 1.68, 4.30); between-cohort heterogeneity ranged from negligible to moderate (p: 0.300 to &lt; 0.001). The association between RRs of obesity by income was lowest in Sweden than in other cohorts. Conclusions There was a social gradient by maternal education on the risk of childhood obesity in all included cohorts. The SES associations measured by income were more heterogeneous and differed between Sweden versus the other national cohorts; these findings may be attributable to policy differences, including preschool policies, maternity leave, a ban on advertising to children, and universal free school meals.

Place, publisher, year, edition, pages
Springer Nature, 2022
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:liu:diva-187410 (URN)10.1038/s41366-022-01171-7 (DOI)000823341900001 ()35821522 (PubMedID)
Note

Funding Agencies|Canadian Institutes of Health Research [OCO-79897, MOP-89886, MSH-95353, ROG-110537]; Linkoping University

Available from: 2022-08-22 Created: 2022-08-22 Last updated: 2023-12-22Bibliographically approved
Dietrich, F., Barcenilla, H., Tavira Iglesias, B., Wahlberg, J., Achenbach, P., Ludvigsson, J. & Casas, R. (2022). Immune response differs between intralymphatic or subcutaneous administration of GAD-alum in individuals with recent onset type 1 diabetes. Diabetes/Metabolism Research Reviews, 38(3), Article ID e3500.
Open this publication in new window or tab >>Immune response differs between intralymphatic or subcutaneous administration of GAD-alum in individuals with recent onset type 1 diabetes
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2022 (English)In: Diabetes/Metabolism Research Reviews, ISSN 1520-7552, E-ISSN 1520-7560, Vol. 38, no 3, article id e3500Article in journal (Refereed) Published
Abstract [en]

Aims: Immunomodulation with autoantigens potentially constitutes a specific and safe treatment for type 1 diabetes (T1D). Studies with GAD-alum administrated subcutaneously have shown to be safe, but its efficacy has been inconclusive. Administration of GAD-alum into the lymph nodes, aimed to optimise antigen presentation, has shown promising results in an open-label clinical trial. Herein, we compared the immune response of the individuals included in the trial with a group who received GAD-alum subcutaneously in a previous study.

Materials and methods: Samples from T1D individuals collected 15 months after administration of either three doses 1 month apart of 4 mu g GAD-alum into lymph nodes (LN, n = 12) or two doses 1 month apart of 20 mu g subcutaneously (SC, n = 12) were studied. GADA, GADA subclasses, GAD(65)-induced cytokines, peripheral blood mononuclear cell proliferation, and T cells markers were analysed.

Results: Low doses of GAD-alum into the lymph nodes induced higher GADA levels than higher doses administrated subcutaneously. Immune response in the LN group was characterised by changes in GADA subclasses, with a relative reduction of IgG1 and enhanced IgG2, IgG3, and IgG4 proportion, higher GAD(65)-induced secretion of IL-5, IL-10, and TNF-alpha, and reduction of cell proliferation and CD8(+) T cells. These changes were not observed after subcutaneous (SC) injections of GAD-alum.

Conclusions: GAD-specific immune responses 15 months after lymph node injections of GAD-alum differed from the ones induced by SC administration of the same autoantigen.

Place, publisher, year, edition, pages
John Wiley & Sons, 2022
Keywords
autoantigen; GAD-alum; intralymphatic; lymph nodes; subcutaneous; type 1 diabetes
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:liu:diva-181078 (URN)10.1002/dmrr.3500 (DOI)000715167400001 ()34611978 (PubMedID)2-s2.0-85116860606 (Scopus ID)
Note

Funding Agencies: Swedish Diabetes Research Foundation; Swedish Child Diabetes Foundation; Diamyd Medical

Available from: 2021-11-18 Created: 2021-11-18 Last updated: 2022-10-12Bibliographically approved
Kordonouri, O., Cuthbertson, D., Bélteky, M., Aschemeier-Fuchs, B., White, N. H., Cummings, E., . . . Ludvigsson, J. (2022). Infections in the first year of life and development of beta cell autoimmunity and clinical type 1 diabetes in high-risk individuals: the TRIGR cohort. Diabetologia, 65, 2098-2107
Open this publication in new window or tab >>Infections in the first year of life and development of beta cell autoimmunity and clinical type 1 diabetes in high-risk individuals: the TRIGR cohort
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2022 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 65, p. 2098-2107Article in journal (Refereed) Published
Abstract [en]

Aims/hypothesis Accumulated data suggest that infections in early life contribute to the development of type 1 diabetes. Using data from the Trial to Reduce IDDM in the Genetically at Risk (TRIGR), we set out to assess whether children who later developed diabetes-related autoantibodies and/or clinical type 1 diabetes had different exposure to infections early in life compared with those who did not. Methods A cohort of 2159 children with an affected first-degree relative and HLA-conferred susceptibility to type 1 diabetes were recruited between 2002 and 2007 and followed until 2017. Infections were registered prospectively. The relationship between infections in the first year of life and the development of autoantibodies or clinical type 1 diabetes was analysed using univariable and multivariable Cox regression models. As this study was exploratory, no adjustment was made for multiple comparisons. Results Adjusting for HLA, sex, breastfeeding duration and birth order, those who had seven or more infections during their first year of life were more likely to develop at least one positive type 1 diabetes-related autoantibody (p=0.028, HR 9.166 [95% CI 1.277, 65.81]) compared with those who had no infections. Those who had their first viral infection aged between 6 and 12 months were less likely to develop at least one positive type 1 diabetes-related antibody (p=0.043, HR 0.828 [95% CI 0.690, 0.994]) or multiple antibodies (p=0.0351, HR 0.664 [95% CI 0.453, 0.972]). Those who had ever had an unspecified bacterial infection were more likely to develop at least one positive type 1 diabetes-related autoantibody (p=0.013, HR 1.412 [95% CI 1.075, 1.854]), to develop multiple antibodies (p=0.037, HR 1.652 [95% CI 1.030, 2.649]) and to develop clinical type 1 diabetes (p=0.011, HR 2.066 [95% CI 1.182, 3.613]). Conclusions/interpretation We found weak support for the assumption that viral infections early in life may initiate the autoimmune process or later development of type 1 diabetes. In contrast, certain bacterial infections appeared to increase the risk of both multiple autoantibodies and clinical type 1 diabetes.

Place, publisher, year, edition, pages
Springer, 2022
Keywords
Autoimmunity; Children; Early infections; TRIGR; Type 1 diabetes
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:liu:diva-188588 (URN)10.1007/s00125-022-05786-3 (DOI)000852089300001 ()36083343 (PubMedID)
Note

Funding Agencies|Linkoping University; Eunice Kennedy Shriver National Institute of Child Health and Human Development [HD040364, HD042444, HD051997]; Special Statutory Funding Program for Type 1 Diabetes Research; Canadian Institutes of Health Research; JDRF; Academy of Finland; European Foundation for the Study of Diabetes/JDRF/Novo Nordisk focused research grant; Commission of the European Communities via the Quality of Life and Management of Living Resources Program [QLK1-2002-00372]

Available from: 2022-09-19 Created: 2022-09-19 Last updated: 2023-02-21Bibliographically approved
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ORCID iD: ORCID iD iconorcid.org/0000-0003-1695-5234

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