226 results on '"Ludvigsson, Johnny"'
Search Results
2. Assisting the implementation of screening for type 1 diabetes by using artificial intelligence on publicly available data
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Teixeira, Pedro F., Battelino, Tadej, Carlsson, Anneli, Gudbjörnsdottir, Soffia, Hannelius, Ulf, von Herrath, Matthias, Knip, Mikael, Korsgren, Olle, Elding Larsson, Helena, Lindqvist, Anton, Ludvigsson, Johnny, Lundgren, Markus, Nowak, Christoph, Pettersson, Paul, Pociot, Flemming, Sundberg, Frida, Åkesson, Karin, Lernmark, Åke, and Forsander, Gun
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- 2024
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3. Progression of type 1 diabetes is associated with high levels of soluble PD-1 in islet autoantibody-positive children
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Bruzzaniti, Sara, Piemonte, Erica, Bruzzese, Dario, Lepore, Maria Teresa, Strollo, Rocky, Izzo, Lavinia, Di Candia, Francesca, Franzese, Adriana, Bifulco, Maurizio, Mozzillo, Enza, Ludvigsson, Johnny, Matarese, Giuseppe, and Galgani, Mario
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- 2024
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4. Estimated glucose disposal rate is associated with retinopathy and kidney disease in young people with type 1 diabetes: a nationwide observational study
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Linn, Wedén, Persson, Martina, Rathsman, Björn, Ludvigsson, Johnny, Lind, Marcus, Andersson Franko, Mikael, and Nyström, Thomas
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- 2023
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5. Infant gut microbiome composition correlated with type 1 diabetes acquisition in the general population: the ABIS study
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Bélteky, Malin, Milletich, Patricia L., Ahrens, Angelica P., Triplett, Eric W., and Ludvigsson, Johnny
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- 2023
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6. Determination of autoantibodies in type 2 diabetes: one simple way to improve classification
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Ludvigsson, Johnny
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- 2023
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7. 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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Kordonouri, Olga, Cuthbertson, David, Belteky, Malin, Aschemeier-Fuchs, Bärbel, White, Neil H., Cummings, Elisabeth, Knip, Mikael, and Ludvigsson, Johnny
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- 2022
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8. 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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Bruzzaniti, Sara, Piemonte, Erica, Mozzillo, Enza, Bruzzese, Dario, Lepore, Maria Teresa, Carbone, Fortunata, de Candia, Paola, Strollo, Rocky, Porcellini, Antonio, Marigliano, Marco, Maffeis, Claudio, Bifulco, Maurizio, Ludvigsson, Johnny, Franzese, Adriana, Matarese, Giuseppe, and Galgani, Mario
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- 2022
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9. Risk factors for nephropathy in persons with type 1 diabetes: a population-based study
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Seyed Ahmadi, Shilan, Pivodic, Aldina, Svensson, Ann-Marie, Wedel, Hans, Rathsman, Björn, Nyström, Thomas, Ludvigsson, Johnny, and Lind, Marcus
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- 2022
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10. Intra-lymphatic administration of GAD-alum in type 1 diabetes: long-term follow-up and effect of a late booster dose (the DIAGNODE Extension trial)
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Casas, Rosaura, Dietrich, Fabrícia, Puente-Marin, Sara, Barcenilla, Hugo, Tavira, Beatriz, Wahlberg, Jeannette, Achenbach, Peter, and Ludvigsson, Johnny
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- 2022
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11. HbA1c and the risk of developing peripheral neuropathy in childhood‐onset type 1 diabetes: A follow‐up study over 3 decades.
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Baldimtsi, Evangelia, Amezcua, Salvador, Ulander, Martin, Hyllienmark, Lars, Olausson, Håkan, Ludvigsson, Johnny, and Wahlberg, Jeanette
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TYPE 1 diabetes ,PERIPHERAL neuropathy ,DIABETIC nephropathies ,NERVE conduction studies ,DIABETIC retinopathy ,DIABETIC neuropathies ,DIABETES complications - Abstract
Aims: We have evaluated long‐term weighted mean HbA1c (wHbA1c), HbA1c variability, diabetes duration, and lipid profiles in relation to the development of diabetic peripheral neuropathy (DPN), nephropathy, and retinopathy in childhood‐onset type 1 diabetes. Materials and Methods: In a longitudinal cohort study, 49 patients (21 women) with childhood‐onset type 1 diabetes were investigated with neurophysiological measurements, blood tests, and clinical examinations after a diabetes duration of 7.7 (±3.3) years (baseline) and followed with repeated examinations for 30.6 (±5.2) years. We calculated wHbA1c by integrating the area under all HbA1c values since the diabetes diagnosis. Lipid profiles were analysed in relation to the presence of DPN. Long‐term fluctuations of HbA1c variability were computed as the standard deviation of all HbA1c measurements. Data regarding the presence of other diabetes complications were retrieved from medical records. Results: In this follow‐up study, 51% (25/49) of the patients fulfilled electrophysiological criteria for DPN. In nerve conduction studies, there was a deterioration in the amplitudes and conduction velocities for the median, peroneal, and sural nerves over time. Patients with DPN had a longer duration of diabetes, higher wHbA1c, and increased HbA1c variability. The lowest wHbA1c value associated with the development of DPN was 62 mmol/mol (7.8%). The presence of albuminuria and retinopathy was positively correlated with the presence of neuropathy. Conclusions: More than half of the patients had developed DPN after 30 years. None of the patients who developed DPN had a wHbA1c of less than 62 mmol/mol (7.8%). [ABSTRACT FROM AUTHOR]
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- 2024
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12. Characterisation of enterovirus RNA detected in the pancreas and other specimens of live patients with newly diagnosed type 1 diabetes in the DiViD study
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Oikarinen, Sami, Krogvold, Lars, Edwin, Bjørn, Buanes, Trond, Korsgren, Olle, Laiho, Jutta E., Oikarinen, Maarit, Ludvigsson, Johnny, Skog, Oskar, Anagandula, Mahesh, Frisk, Gun, Hyöty, Heikki, and Dahl-Jørgensen, Knut
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- 2021
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13. Overweight or obesity, weight variability and the risk of retinopathy in type 1 diabetes.
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Nyström, Thomas, Andersson Franko, Mikael, Ludvigsson, Johnny, Lind, Marcus, and Persson, Martina
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TYPE 1 diabetes ,OBESITY ,WEIGHT loss ,INSULIN pumps ,WEIGHT gain ,CHILDHOOD obesity - Abstract
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]
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- 2024
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14. Prevalence and Predictive Factors for Celiac Disease in Children With Type 1 Diabetes: Whom and When to Screen? A Nationwide Longitudinal Cohort Study of Swedish Children.
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Lindgren, Marie, Norström, Fredrik, Persson, Martina, Elding Larsson, Helena, Forsander, Gun, Åkesson, Karin, Samuelsson, Ulf, Ludvigsson, Johnny, and Carlsson, Annelie
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CELIAC disease ,TYPE 1 diabetes ,MEDICAL screening ,DIAGNOSIS of diabetes ,COHORT analysis ,LONGITUDINAL method - Abstract
OBJECTIVE: To examine the prevalence and predictive factors for celiac disease (CD) after a diagnosis of type 1 diabetes (T1D) in children and adolescents, to improve the current screening guidelines. RESEARCH DESIGN AND METHODS: The association between sex, age at T1D diagnosis, HLA, and diabetes autoantibodies, and a diagnosis of CD was examined in 5,295 children with T1D from the Better Diabetes Diagnosis study in Sweden. RESULTS: The prevalence of biopsy-proven CD was 9.8%, of which 58.2% already had a CD diagnosis before or at T1D onset. Almost all, 95.9%, were diagnosed with CD within 5 years after the T1D diagnosis. Younger age at the T1D diagnosis and being homozygote for DQ2 increased the risk of CD after T1D, but neither sex nor diabetes-related autoantibodies were associated with the risk. CONCLUSIONS: Age at and time after diabetes diagnosis should be considered in screening guidelines for CD in children with T1D. [ABSTRACT FROM AUTHOR]
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- 2024
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15. Efficacy of GAD-alum immunotherapy associated with HLA-DR3-DQ2 in recently diagnosed type 1 diabetes
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Hannelius, Ulf, Beam, Craig A., and Ludvigsson, Johnny
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- 2020
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16. Cumulative incidence of type 1 diabetes in two cohorts of children with different national gluten recommendations in infancy.
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Lindgren, Marie, Palmkvist, Elsa, Norström, Fredrik, Cerqueiro Bybrant, Mara, Myleus, Anna, Samuelsson, Ulf, Ludvigsson, Johnny, and Carlsson, Annelie
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TYPE 1 diabetes ,GLUTEN ,INFANTS ,PREMATURE infants ,CELIAC disease - Abstract
Aims: Between 1985 and 1996, Sweden experienced an "epidemic" of celiac disease with a fourfold increase in incidence in young children. Timing and amount of gluten introduced during infancy have been thought to explain this "epidemic". We aimed to study whether the cumulative incidence of type 1 diabetes differs between children born during the "epidemic" compared to children born after. Methods: This is a national register study in Sweden comparing the cumulative incidence of type 1 diabetes in two birth cohorts of 240 844 children 0–17 years old born 1992–1993, during the "epidemic", and 179 530 children born 1997–1998, after the "epidemic". Children diagnosed with type 1 diabetes were identified using three national registers. Results: The cumulative incidence of type 1 diabetes by the age of 17 was statistically significantly higher in those born after the "epidemic" 0.77% than in those born during the "epidemic" 0.68% (p < 0.001). Conclusion: The incidence of type 1 diabetes is higher in those born after the epidemic compared to those born during the epidemic, which does not support the hypothesis that gluten introduction increases the incidence of T1D. Changes in gluten introduction did not halt the increased incidence of type 1 diabetes in Sweden. [ABSTRACT FROM AUTHOR]
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- 2024
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17. A 1‐year pilot study of intralymphatic injections of GAD‐alum in individuals with latent autoimmune diabetes in adults (LADA) with signs of high immunity: No safety concerns and resemblance to juvenile type 1 diabetes.
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Hals, Ingrid K., Balasuriya, Chandima, Casas, Rosaura, Ludvigsson, Johnny, Björklund, Anneli, and Grill, Valdemar
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TYPE 1 diabetes ,GLUTAMATE decarboxylase ,HLA histocompatibility antigens ,IMMUNITY ,PILOT projects - Abstract
Aims: To test, for the first time in latent autoimmune diabetes in adults (LADA), the effects of autoantigen‐specific immunotherapy by intralymphatic administration of aluminium‐formulated recombinant human glutamic acid decarboxylase 65 (GAD‐alum); specifically, to test if this treatment is safe, to test whether it induces a strong immunological response akin to a similar protocol in type 1 diabetes and to look for associations with preserved beta‐cell function. Materials and Methods: Three GAD‐alum injections, 4 μg each, were administered 1 month apart into an inguinal lymph node in 14 people with newly diagnosed LADA (age 30‐62 years) presenting with high levels of antibodies against glutamic acid decarboxylase (GADA). Adverse effects, immunological variables and beta‐cell function were monitored, with detailed measurements at 5 and 12 months from baseline. Results: Clinical adverse effects were minor and transient and measured laboratory variables were unaffected. All participants completed the study. Treatment raised levels of GADA, elicited strong effects on reactivity of peripheral blood mononuclear cells to GAD and raised cytokine/chemokine levels. Beta‐cell function appeared stable preferentially in the seven participants carrying human leukocyte antigen (HLA) haplotypes DR3DQ2, as assessed by C‐peptide glucagon tests (P < 0.05 vs. seven non‐carriers). Conclusion: Intralymphatic treatment with GAD‐alum in LADA is without clinical or other safety concerns over a 12‐month period. As in a similar protocol used in type 1 diabetes, treatment exerts a strong immunological impact and is compatible with protection of beta‐cell function preferentially in HLA‐DR3DQ2 LADA patients. These findings pave the way for a randomized controlled trial in this important subgroup of LADA patients. [ABSTRACT FROM AUTHOR]
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- 2023
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18. Important denominator between autoimmune comorbidities: a review of class II HLA, autoimmune disease, and the gut.
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Berryman, Meghan A., Ilonen, Jorma, Triplett, Eric W., and Ludvigsson, Johnny
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AUTOIMMUNE diseases ,HLA histocompatibility antigens ,GUT microbiome ,COMORBIDITY ,TYPE 1 diabetes - Abstract
Human leukocyte antigen (HLA) genes are associated with more diseases than any other region of the genome. Highly polymorphic HLA genes produce variable haplotypes that are specifically correlated with pathogenically different autoimmunities. Despite differing etiologies, however, many autoimmune disorders share the same risk-associated HLA haplotypes often resulting in comorbidity. This shared risk remains an unanswered question in the field. Yet, several groups have revealed links between gut microbial community composition and autoimmune diseases. Autoimmunity is frequently associated with dysbiosis, resulting in loss of barrier function and permeability of tight junctions, which increases HLA class II expression levels and thus further influences the composition of the gut microbiome. However, autoimmunerisk-associated HLA haplotypes are connected to gut dysbiosis long before autoimmunity even begins. This review evaluates current research on the HLAmicrobiome-autoimmunity triplex and proposes that pre-autoimmune bacterial dysbiosis in the gut is an important determinant between autoimmune comorbidities with systemic inflammation as a common denominator. [ABSTRACT FROM AUTHOR]
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- 2023
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19. Single-cell RNAseq identifies clonally expanded antigen-specific T-cells following intradermal injection of gold nanoparticles loaded with diabetes autoantigen in humans.
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Hanna, Stephanie J., Thayer, Terri C., Robinson, Emma J. S., Vinh, Ngoc-Nga, Williams, Nigel, Landry, Laurie G., Andrews, Robert, Qi Zhuang Siah, Leete, Pia, Wyatt, Rebecca, McAteer, Martina A., Nakayama, Maki, Wong, F. Susan, Yang, Jennie H. M., Tree, Timothy I. M., Ludvigsson, Johnny, Dayan, Colin M., and Tatovic, Danijela
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INTRADERMAL injections ,GOLD nanoparticles ,T cells ,TYPE 1 diabetes ,PEPTIDES - Abstract
Gold nanoparticles (GNPs) have been used in the development of novel therapies as a way of delivery of both stimulatory and tolerogenic peptide cargoes. Here we report that intradermal injection of GNPs loaded with the proinsulin peptide C19-A3, in patients with type 1 diabetes, results in recruitment and retention of immune cells in the skin. These include large numbers of clonally expanded Tcells sharing the same paired T-cell receptors (TCRs) with activated phenotypes, half of which, when the TCRs were re-expressed in a cell-based system, were confirmed to be specific for either GNP or proinsulin. All the identified goldspecific clones were CD8+, whilst proinsulin-specific clones were both CD8+ and CD4+. Proinsulin-specific CD8+ clones had a distinctive cytotoxic phenotype with overexpression of granulysin (GNLY) and KIR receptors. Clonally expanded antigen-specific T cells remained in situ for months to years, with a spectrum of tissue resident memory and effector memory phenotypes. As the T-cell response is divided between targeting the gold core and the antigenic cargo, this offers a route to improving resident memory T-cells formation in response to vaccines. In addition, our scRNAseq data indicate that focusing on clonally expanded skin infiltrating T-cells recruited to intradermally injected antigen is a highly efficient method to enrich and identify antigen-specific cells. This approach has the potential to be used to monitor the intradermal delivery of antigens and nanoparticles for immune modulation in humans. [ABSTRACT FROM AUTHOR]
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- 2023
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20. Characteristics of slow progression to diabetes in multiple islet autoantibody-positive individuals from five longitudinal cohorts: the SNAIL study
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Long, Anna E., Wilson, Isabel V., Becker, Dorothy J., Libman, Ingrid M., Arena, Vincent C., Wong, F. Susan, Steck, Andrea K., Rewers, Marian J., Yu, Liping, Achenbach, Peter, Casas, Rosaura, Ludvigsson, Johnny, Williams, Alistair J. K., and Gillespie, Kathleen M.
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- 2018
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21. Human leukocyte antigen-dependent colonization of Lactobacillus in the early-life gut.
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Berryman, Meghan A., Triplett, Eric W., and Ludvigsson, Johnny
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LACTOBACILLUS ,HLA histocompatibility antigens ,LEUCOCYTES ,CHILD patients ,GUT microbiome ,COMPOSITION of breast milk - Abstract
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]
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- 2023
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22. No association between incidence of type 1 diabetes and rotavirus vaccination in Swedish children.
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Rangert, Amanda, Oldin, Carin, Golsäter, Marie, Ludvigsson, Johnny, and Åkesson, Karin
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ROTAVIRUS vaccines ,TYPE 1 diabetes ,VACCINATION of children ,CHILD health services ,ROTAVIRUS diseases - Abstract
Background: Rotavirus infection is a potential trigger of type 1 diabetes (T1D) and rotavirus vaccination is hypothesized to decrease the incidence of T1D. In Sweden, rotavirus vaccination was introduced in 2014 in two regions and from 2019, nationwide. This study aims to investigate the association between rotavirus vaccination and incidence of T1D in Swedish children and whether rotavirus vaccination is associated with a change in clinical manifestation at diabetes onset. Methods: A nationwide register-based study with all Swedish children <15 years of age, diagnosed with T1D 2009-2019 was conducted. 7893 children were retrieved. Nationwide vaccine coverage was collected from Child Health Services. Three vaccine groups were created: I: Vaccination start 2014; II: Gradual vaccination start 2016-2018; III: No vaccination. Incidence rates of T1D before (2009-2014) and after (2014-2019) introduction of rotavirus vaccine were compared. Findings: The mean incidence of T1D in children <15 years was 42·61 per 100 000 during the observed period. When comparing the years before and after 2014 the incidence rate ratio (IRR) for children <5 years was 0·86 in group I (p=0·10), 0·85 (p=0·05) in group II and 0·87 (p=0·06) in group III. A similar IRR reduction was also seen among older children who received no vaccine. Children developing or not developing T1D were vaccinated to the same extent. No differences regarding clinical manifestation at onset associated with rotavirus vaccination were seen. Interpretation: There is no association between rotavirus vaccination in children and incidence or clinical manifestation of T1D. [ABSTRACT FROM AUTHOR]
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- 2023
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23. Antibodies to post-translationally modified insulin as a novel biomarker for prediction of type 1 diabetes in children
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Strollo, Rocky, Vinci, Chiara, Napoli, Nicola, Pozzilli, Paolo, Ludvigsson, Johnny, and Nissim, Ahuva
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- 2017
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24. Effect of simultaneous vaccination with H1N1 and GAD-alum on GAD65-induced immune response
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Tavira, Beatriz, Cheramy, Mikael, Axelsson, Stina, Åkerman, Linda, Ludvigsson, Johnny, and Casas, Rosaura
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- 2017
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25. GAD vaccine reduces insulin loss in recently diagnosed type 1 diabetes: findings from a Bayesian meta-analysis
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Beam, Craig A., MacCallum, Colleen, Herold, Kevan C., Wherrett, Diane K., Palmer, Jerry, Ludvigsson, Johnny, and the Type 1 Diabetes TrialNet Study Group
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- 2017
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26. Children’s Views on Long-Term Screening for Type 1 Diabetes
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Swartling, Ulrica, Helgesson, Gert, Ludvigsson, Johnny, Hansson, Mats G., and Nordgren, Anders
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- 2014
27. Low maternal education increases the risk of Type 1 Diabetes, but not other autoimmune diseases: a mediating role of childhood BMI and exposure to serious life events.
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White, Pär Andersson, Faresjö, Tomas, Jones, Michael P., and Ludvigsson, Johnny
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TYPE 1 diabetes ,AUTOIMMUNE diseases ,CROHN'S disease ,JUVENILE idiopathic arthritis ,INCOME ,INFANTS ,INFANTS' supplies - Abstract
The objective of this paper was to investigate if socioeconomic status (SES), measured by maternal education and household income, influenced the risk of developing autoimmune disease (Type 1 Diabetes, Celiac disease, Juvenile Idiopathic Arthritis, Crohn's disease, Ulcerative colitis, and autoimmune thyroid disease), or age at diagnosis, and to analyse pathways between SES and autoimmune disease. We used data from the All Babies in Southeast Sweden (ABIS) study, a population-based prospective birth cohort, which included children born 1997–1999. Diagnoses of autoimmune disease was collected from the Swedish National Patient Register Dec 2020. In 16,365 individuals, low maternal education, but not household income, was associated with increased risk of Type 1 Diabetes; middle education RR 1.54, 95% CI 1.06, 2.23; P 0.02, low education RR 1.81, 95% CI 1.04, 3.18; P 0.04. Maternal education and household income was not associated with any other autoimmune disease and did not influence the age at diagnosis. Part of the increased risk of Type 1 Diabetes by lower maternal education was mediated by the indirect pathway of higher BMI and higher risk of Serious Life Events (SLE) at 5 years of age. The risk of developing Type 1 Diabetes associated to low maternal education might be reduced by decreasing BMI and SLE during childhood. [ABSTRACT FROM AUTHOR]
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- 2023
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28. Growth and development of islet autoimmunity and type 1 diabetes in children genetically at risk
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Nucci, Anita M., Virtanen, Suvi M., Cuthbertson, David, Ludvigsson, Johnny, Einberg, Ulle, Huot, Celine, Castano, Luis, Aschemeier, Bärbel, Becker, Dorothy J., Knip, Mikael, Krischer, Jeffrey P., Mandrup-Poulsen, Thomas, Arjas, Elias, Läärä, Esa, Lernmark, Åke, Schmidt, Barbara, Åkerblom, Hans K., Hyytinen, Mila, Koski, Katriina, Koski, Matti, Pajakkala, Eeva, Salonen, Marja, Shanker, Linda, Bradley, Brenda, Dosch, Hans Michael, and Dupré, John
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Male ,0301 basic medicine ,Pediatric Obesity ,Heredity ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Breastfeeding ,Autoimmunity ,Overweight ,Child Development ,0302 clinical medicine ,Risk Factors ,Weight management ,Medicine ,Child ,Randomized Controlled Trials as Topic ,education.field_of_study ,Incidence ,Age Factors ,Childhood growth ,Beta cell autoimmunity ,Prognosis ,Infant Formula ,Pedigree ,Europe ,Type 1 diabetes ,Phenotype ,Child, Preschool ,Female ,medicine.symptom ,medicine.medical_specialty ,Adolescent ,Length ,Population ,030209 endocrinology & metabolism ,Risk Assessment ,Article ,Islets of Langerhans ,03 medical and health sciences ,Internal medicine ,Internal Medicine ,Humans ,Genetic Predisposition to Disease ,education ,Genetic risk ,business.industry ,Proportional hazards model ,Insulin ,Australia ,Infant, Newborn ,Autoantibody ,Infant ,Adolescent Development ,Weight ,medicine.disease ,Bottle Feeding ,Diabetes Mellitus, Type 1 ,030104 developmental biology ,North America ,business - Abstract
Aims/hypothesis: We aimed to evaluate the relationship between childhood growth measures and risk of developing islet autoimmunity (IA) and type 1 diabetes in children with an affected first-degree relative and increased HLA-conferred risk. We hypothesised that being overweight or obese during childhood is associated with a greater risk of IA and type 1 diabetes. Methods: Participants in a randomised infant feeding trial (N = 2149) were measured at 12 month intervals for weight and length/height and followed for IA (at least one positive out of insulin autoantibodies, islet antigen-2 autoantibody, GAD autoantibody and zinc transporter 8 autoantibody) and development of type 1 diabetes from birth to 10–14 years. In this secondary analysis, Cox proportional hazard regression models were adjusted for birthweight and length z score, sex, HLA risk, maternal type 1 diabetes, mode of delivery and breastfeeding duration, and stratified by residence region (Australia, Canada, Northern Europe, Southern Europe, Central Europe and the USA). Longitudinal exposures were studied both by time-varying Cox proportional hazard regression and by joint modelling. Multiple testing was considered using family-wise error rate at 0.05. Results: In the Trial to Reduce IDDM in the Genetically at Risk (TRIGR) population, 305 (14.2%) developed IA and 172 (8%) developed type 1 diabetes. The proportions of children overweight (including obese) and obese only were 28% and 9% at 10 years, respectively. Annual growth measures were not associated with IA, but being overweight at 2–10 years of life was associated with a twofold increase in the development of type 1 diabetes (HR 2.39; 95% CI 1.46, 3.92; p < 0.001 in time-varying Cox regression), and similarly with joint modelling. Conclusions/interpretation: In children at genetic risk of type 1 diabetes, being overweight at 2–10 years of age is associated with increased risk of progression from multiple IA to type 1 diabetes and with development of type 1 diabetes, but not with development of IA. Future studies should assess the impact of weight management strategies on these outcomes. Trial registration: ClinicalTrials.gov NCT00179777 Graphical abstract: [Figure not available: see fulltext.]
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- 2021
29. Intralymphatic GAD-alum Injection Modulates B Cell Response and Induces Follicular Helper T Cells and PD-1+CD8+T Cells in Patients With Recent-Onset Type 1 Diabetes
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Barcenilla, Hugo, Pihl, Mikael, Wahlberg, Jeanette, Ludvigsson, Johnny, and Casas, Rosaura
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antigen-specific immunotherapy ,type 1 diabetes ,GAD-alum ,mass cytometry (CyTOF) ,follicular T helper cells ,T cell exhaustion ,B cell response ,T1D ,Immunologi inom det medicinska området ,Immunology in the medical area - Abstract
Antigen-specific immunotherapy is an appealing strategy to preserve beta-cell function in type 1 diabetes, although the approach has yet to meet its therapeutic endpoint. Direct administration of autoantigen into lymph nodes has emerged as an alternative administration route that can improve the efficacy of the treatment. In the first open-label clinical trial in humans, injection of aluminum-formulated glutamic acid decarboxylase (GAD-alum) into an inguinal lymph node led to the promising preservation of C-peptide in patients with recent-onset type 1 diabetes. The treatment induced a distinct immunomodulatory effect, but the response at the cell level has not been fully characterized. Here we used mass cytometry to profile the immune landscape in peripheral blood mononuclear cells from 12 participants of the study before and after 15 months of treatment. The immunomodulatory effect of the therapy included reduction of naive and unswitched memory B cells, increase in follicular helper T cells and expansion of PD-1+ CD69+ cells in both CD8+ and double negative T cells. In vitro stimulation with GAD(65) only affected effector CD8+ T cells in samples collected before the treatment. However, the recall response to antigen after 15 months included induction of CXCR3+ and CD11c+Tbet+ B cells, PD-1+ follicular helper T cells and exhausted-like CD8+ T cells. This study provides a deeper insight into the immunological changes associated with GAD-alum administration directly into the lymph nodes. Funding Agencies|Barndiabetesfonden (Swedish Child Diabetes Foundation); Swedish Diabetes research foundation; Diamyd Medical
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- 2022
30. Type 1 diabetes in low and middle-income countries - Tanzania a streak of hope.
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Ludvigsson, Johnny, Edna, Majaliwa, and Ramaiya, Kaushik
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TYPE 1 diabetes ,MIDDLE-income countries ,DIABETES in children ,LOW-income countries ,YOUNG adults ,TYPE 2 diabetes - Abstract
Introduction: In several of the Low and Middle Income countries, many patients with Type 1 diabetes (T1D) are most probably not diagnosed at all which may contribute to their low incidence. As an example of a country with low income and poor resources, we have chosen to study T1D in children/young people in Tanzania. Methods: Analyses of casebooks and statistics at several Tanzanian hospitals treating young patients with insulin dependent diabetes, usually Type 1 diabetes, and collection of information from different organisations such a Tanzanian Diabetes Association, Life for a Child, Changing Diabetes in Children and World Diabetes Foundation. Results: The incidence in several areas is low. However, a lot of data are often missing at studied clinics and therefore the incidence might be higher, and with increased awareness in recent years the number of patients has increased manyfolds. Most patients present with typical symptoms and signs of T1D, and a high proportion with plausible ketoacidosis, although this proportion has decreased from about 90% to about 40% in recent decades. Many patients have poor blood glucose control, and complications often develop already after short diabetes duration. In recent years resources have increased, awareness has increased and diabetes clinics started where staff has got training. Conclusions: There are problems with diabetes care in Tanzania but several facts give hope for the future. [ABSTRACT FROM AUTHOR]
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- 2023
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31. Severe COVID-19 Infection in Type 1 and Type 2 Diabetes During the First Three Waves in Sweden.
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Edqvist, Jon, Lundberg, Christina, Andreasson, Karin, Björck, Lena, Dikaiou, Pigi, Ludvigsson, Johnny, Lind, Marcus, Adiels, Martin, and Rosengren, Annika
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TYPE 2 diabetes ,TYPE 1 diabetes ,COVID-19 ,INTENSIVE care units ,SOCIOECONOMIC factors - Abstract
OBJECTIVE: Type 2 diabetes is an established risk factor for hospitalization and death in COVID-19 infection, while findings with respect to type 1 diabetes have been diverging. RESEARCH DESIGN AND METHODS: Using nationwide health registries, we identified all patients aged ≥18 years with type 1 and type 2 diabetes in Sweden. Odds ratios (ORs) describe the general and age-specific risk of being hospitalized, need for intensive care, or dying, adjusted for age, socioeconomic factors, and coexisting conditions, compared with individuals without diabetes. Machine learning models were used to find predictors of outcomes among individuals with diabetes positive for COVID-19. RESULTS: Until 30 June 2021, we identified 365 (0.71%) and 11,684 (2.31%) hospitalizations in 51,402 and 504,337 patients with type 1 and 2 diabetes, respectively, with 67 (0.13%) and 2,848 (0.56%) requiring intensive care unit (ICU) care and 68 (0.13%) and 4,020 (0.80%) dying (vs 7,824,181 individuals without diabetes [41,810 hospitalizations (0.53%), 8,753 (0.11%) needing ICU care, and 10,160 (0.13%) deaths). Although those with type 1 diabetes had moderately raised odds of being hospitalized (multiple-adjusted OR 1.38 [95% CI 1.24–1.53]), there was no independent effect on ICU care or death (OR of 1.21 [95% CI 0.94–1.52] and 1.13 [95% CI 0.88–1.48], respectively). Age and socioeconomic factors were the dominating features for predicting hospitalization and death in both types of diabetes. CONCLUSIONS: Type 2 diabetes was associated with increased odds for all outcomes, whereas patients with type 1 diabetes had moderately increased odds of hospitalization but not ICU care and death. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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32. Intralymphatic glutamic acid decarboxylase administration in type 1 diabetes patients induced a distinctive early immune response in patients with DR3DQ2 haplotype.
- Author
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Puente-Marin, Sara, Dietrich, Fabrícia, Achenbach, Peter, Barcenilla, Hugo, Ludvigsson, Johnny, and Casas, Rosaura
- Subjects
GLUTAMATE decarboxylase ,HAPLOTYPES ,TYPE 1 diabetes ,IMMUNE response ,PEOPLE with diabetes - Abstract
GAD-alum given into lymph nodes to Type 1 diabetes (T1D) patients participating in a multicenter, randomized, placebo-controlled double-blind study seemed to have a positive effect for patients with DR3DQ2 haplotype, who showed better preservation of C-peptide than the placebo group. Here we compared the immunomodulatory effect of GAD-alum administered into lymph nodes of patients with T1D versus placebo with focus on patients with DR3DQ2 haplotype. Methods: GAD autoantibodies, GADA subclasses, GAD
65 -induced cytokine secretion (Luminex panel) and proliferation of peripheral mononuclear cells were analyzed in T1D patients (n=109) who received either three intra-lymphatic injections (one month apart) with 4 μg GAD-alum and oral vitamin D supplementation (2000 IE daily for 120 days), or placebo. Results: Higher GADA, GADA subclasses, GAD65 -induced proliferation and cytokine secretion was observed in actively treated patients after the second injection of GAD-alum compared to the placebo group. Following the second injection of GAD-alum, actively treated subjects with DR3DQ2 haplotype had higher GAD65 -induced secretion of several cytokine (IL4, IL5, IL7, IL10, IL13, IFNg, GM-CSF and MIP1b) and proliferation compared to treated individuals without DR3DQ2. Stratification of samples from GAD-alum treated patients according to C-peptide preservation at 15 months revealed that "good responder" individuals with better preservation of C-peptide secretion, independently of the HLA haplotype, had increased GAD65 -induced proliferation and IL13 secretion at 3 months, and a 2,5-fold increase of IL5 and IL10 as compared to "poor responders". The second dose of GAD-alum also induced a more pronounced cytokine secretion in "good responders" with DR3DQ2, compared to few "good responders" without DR3DQ2 haplotype. Conclusion: Patients with DR3DQ2 haplotype had a distinct early cellular immune response to GAD-alum injections into the lymph node, and predominant GAD65 - induced IL13 secretion and proliferation that seems to be associated with a better clinical outcome. If confirmed in the ongoing larger randomized double-blind placebo-controlled clinical trial (DIAGNODE-3), including only patients carrying DR3DQ2 haplotype, these results might be used as early surrogate markers for clinical efficacy. [ABSTRACT FROM AUTHOR]- Published
- 2023
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- View/download PDF
33. Also the parents of children with type 1 diabetes need psychological support.
- Author
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Ludvigsson, Johnny
- Subjects
- *
TYPE 1 diabetes , *INSULIN pumps , *PARENTS , *DIABETES in children , *GLYCEMIC control , *YOUNG adults - Abstract
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]
- Published
- 2024
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- View/download PDF
34. Risk of renal disease in patients with both type 1 diabetes and coeliac disease
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Mollazadegan, Kaziwe, Fored, Michael, Lundberg, Sigrid, Ludvigsson, Johnny, Ekbom, Anders, Montgomery, Scott M., and Ludvigsson, Jonas F.
- Published
- 2014
- Full Text
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35. Month of birth and the risk of developing type 1 diabetes among children in the Swedish national Better Diabetes Diagnosis Study.
- Author
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Hedlund, Emma, Ludvigsson, Johnny, Elding Larsson, Helena, Forsander, Gun, Ivarsson, Sten, Marcus, Claude, Samuelsson, Ulf, Persson, Martina, and Carlsson, Annelie
- Subjects
- *
TYPE 1 diabetes , *DIABETES in children , *DIAGNOSIS of diabetes , *AUTOANTIBODIES - Abstract
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]
- Published
- 2022
- Full Text
- View/download PDF
36. Impact of HbA1c Followed 32 Years From Diagnosis of Type 1 Diabetes on Development of Severe Retinopathy and Nephropathy: The VISS Study.
- Author
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Arnqvist, Hans J., Westerlund, Malin C., Fredrikson, Mats, Ludvigsson, Johnny, and Nordwall, Maria
- Subjects
TYPE 1 diabetes ,DIABETIC retinopathy ,DIABETIC nephropathies ,KIDNEY diseases ,ALBUMINURIA ,DIAGNOSIS - Abstract
Objective: To evaluate HbA1c followed from diagnosis, as a predictor of severe microvascular complications (i.e., proliferative diabetic retinopathy [PDR] and nephropathy [macroalbuminuria]).Research Design and Methods: In a population-based observational study, 447 patients diagnosed with type 1 diabetes before 35 years of age from 1983 to 1987 in southeast Sweden were followed from diagnosis until 2019. Long-term weighted mean HbA1c (wHbA1c) was calculated by integrating the area under all HbA1c values. Complications were analyzed in relation to wHbA1c categorized into five levels.Results: After 32 years, 9% had no retinopathy, 64% non-PDR, and 27% PDR, and 83% had no microalbuminuria, 9% microalbuminuria, and 8% macroalbuminuria. Patients with near-normal wHbA1c did not develop PDR or macroalbuminuria. The lowest wHbA1c values associated with development of PDR and nephropathy (macroalbuminuria) were 7.3% (56 mmol/mol) and 8.1% (65 mmol/mol), respectively. The prevalence of PDR and macroalbuminuria increased with increasing wHbA1c, being 74% and 44% in the highest category, wHbA1c >9.5% (>80 mmol/mol). In comparison with the follow-up done after 20-24 years' duration, the prevalence of PDR had increased from 14 to 27% and macroalbuminuria from 4 to 8%, and both appeared at lower wHbA1c values.Conclusions: wHbA1c followed from diagnosis is a very strong biomarker for PDR and nephropathy, the prevalence of both still increasing 32 years after diagnosis. To avoid PDR and macroalbuminuria in patients with type 1 diabetes, an HbA1c <7.0% (53 mmol/mol) and as normal as possible should be recommended when achievable without severe hypoglycemia and with good quality of life. [ABSTRACT FROM AUTHOR]- Published
- 2022
- Full Text
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37. Association between treatment effect on C‐peptide preservation and HbA1c in meta‐analysis of glutamic acid decarboxylase (GAD)‐alum immunotherapy in recent‐onset type 1 diabetes.
- Author
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Nowak, Christoph, Hannelius, Ulf, and Ludvigsson, Johnny
- Subjects
GLUTAMATE decarboxylase ,TYPE 1 diabetes ,TREATMENT effectiveness ,GLYCOSYLATED hemoglobin ,C-peptide ,AUTOANTIBODIES - Abstract
B APPENDIX SENSITIVITY ANALYSIS 2 B.1 Using the Quantitative Response (QR) metric to quantify C-peptide treatment effect In order to assess the robustness of the findings regardless of analytical model, we repeated the analysis of the C-peptide effect using a modified version of the QR metric suggested by Krischer and Bundy (Endocrinol Diabetes Metab 2020, PMID 32704564). In brief, the original QR metric quantifies the treatment effect on C-peptide preservation as the difference between the observed C-peptide and the predicted C-peptide after 12 months in recent-onset T1D patients. The association between the treatment effect has not been reported for other investigational treatments, such as for other antigen-specific therapies or immunosuppressive treatments. Keywords: antidiabetic drug; beta cell function; clinical trial; meta-analysis; type 1 diabetes EN antidiabetic drug beta cell function clinical trial meta-analysis type 1 diabetes 1647 1655 9 07/11/22 20220801 NES 220801 BACKGROUND Preservation of insulin secretion in type 1 diabetes (T1D) lowers the risk of complications such as retinopathy and severe hypoglycaemia.1-3 C-peptide preservation - a biomarker for endogenous insulin secretion - is used as a surrogate endpoint in clinical trials assessing beta cell-preserving therapies. [Extracted from the article]
- Published
- 2022
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38. Latent Autoimmune Diabetes in Adults: Background, Safety and Feasibility of an Ongoing Pilot Study With Intra-Lymphatic Injections of GAD-Alum and Oral Vitamin D.
- Author
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Björklund, Anneli, Hals, Ingrid K., Grill, Valdemar, and Ludvigsson, Johnny
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TYPE 1 diabetes ,PILOT projects ,ADULTS ,PANCREATIC beta cells ,CELL physiology - Abstract
Background: Latent Autoimmune Diabetes in Adults (LADA) constitutes around 10% of all diabetes. Many LADA patients gradually lose their insulin secretion and progress to insulin dependency. In a recent trial BALAD (Behandling Av LADa) early insulin treatment compared with sitagliptin failed to preserve insulin secretion, which deteriorated in individuals displaying high levels of antibodies to GAD (GADA). These findings prompted us to evaluate a treatment that directly affects autoimmunity. Intra-lymphatic GAD-alum treatment has shown encouraging results in Type 1 diabetes patients. We therefore tested the feasibility of such therapy in LADA-patients (the GADinLADA pilot study). Material and Methods: Fourteen GADA-positive (>190 RU/ml), insulin-independent patients 30-70 years old, with LADA diagnosed within < 36 months were included in an open-label feasibility trial. They received an intra-nodal injection of 4 mg GAD-alum at Day 1, 30 and 60 plus oral Vitamin D 2000 U/d from screening 30 days before (Day-30) for 4 months if the vitamin D serum levels were below 100 nmol/L (40 µg/ml). Primary objective is to evaluate safety and feasibility. Mixed Meal Tolerance Test and i.v. Glucagon Stimulation Test at baseline and after 5 and 12 months are used for estimation of beta cell function. Results will be compared with those of the recent BALAD study with comparable patient population. Immunological response is followed. Results: Preliminary results show feasibility and safety, with almost stable beta cell function and metabolic control during follow-up so far (5 months). Conclusions: Intra-lymphatic GAD-alum treatment is an option to preserve beta cell function in LADA-patients. An ongoing trial in 14 LADA-patients show feasibility and safety. Clinical and immunological responses will determine how to proceed with future trials. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
39. Update on Treatment of Type 1 Diabetes in Childhood
- Author
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Ludvigsson, Johnny
- Published
- 2013
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40. Pancreatic biopsy by minimal tail resection in live adult patients at the onset of type 1 diabetes: experiences from the DiViD study
- Author
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Krogvold, Lars, Edwin, Bjørn, Buanes, Trond, Ludvigsson, Johnny, Korsgren, Olle, Hyöty, Heikki, Frisk, Gun, Hanssen, Kristian F., and Dahl-Jørgensen, Knut
- Published
- 2014
- Full Text
- View/download PDF
41. Immune Intervention in Children with Type 1 Diabetes
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Ludvigsson, Johnny and for The Linköping Diabetes Immune Intervention study group
- Published
- 2010
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42. Autoantigen Treatment in Type 1 Diabetes: Unsolved Questions on How to Select Autoantigen and Administration Route
- Author
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Ludvigsson, Johnny
- Subjects
autoantigen treatment ,endocrine system diseases ,Glutamate Decarboxylase ,type 1 diabetes ,oral administration ,Injections, Subcutaneous ,Administration, Oral ,Injections, Intralymphatic ,vitamin d ,Review ,Autoantigens ,combination therapy ,lcsh:Chemistry ,Diabetes Mellitus, Type 1 ,intralymphatic treatment ,lcsh:Biology (General) ,lcsh:QD1-999 ,Chemotherapy, Adjuvant ,Animals ,Humans ,Insulin ,Drug Therapy, Combination ,gad-alum ,lcsh:QH301-705.5 ,Proinsulin - Abstract
Autoantigen treatment has been tried for the prevention of type 1 diabetes (T1D) and to preserve residual beta-cell function in patients with a recent onset of the disease. In experimental animal models, efficacy was good, but was insufficient in human subjects. Besides the possible minor efficacy of peroral insulin in high-risk individuals to prevent T1D, autoantigen prevention trials have failed. Other studies on autoantigen prevention and intervention at diagnosis are ongoing. One problem is to select autoantigen/s; others are dose and route. Oral administration may be improved by using different vehicles. Proinsulin peptide therapy in patients with T1D has shown possible minor efficacy. In patients with newly diagnosed T1D, subcutaneous injection of glutamic acid decarboxylase (GAD) bound to alum hydroxide (GAD-alum) can likely preserve beta-cell function, but the therapeutic effect needs to be improved. Intra-lymphatic administration may be a better alternative than subcutaneous administration, and combination therapy might improve efficacy. This review elucidates some actual problems of autoantigen therapy in the prevention and/or early intervention of type 1 diabetes.
- Published
- 2020
43. Glutamic acid decarboxylase injection into lymph nodes: Beta cell function and immune responses in recent onset type 1 diabetes patients
- Author
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Casas, Rosaura, Dietrich, Fabricia, Barcenilla, Hugo, Tavira Iglesias, Beatriz, Wahlberg, Jeanette, Achenbach, Peter, and Ludvigsson, Johnny
- Subjects
Male ,Adolescent ,GAD-alum ,type 1 diabetes ,Immunology ,Administration, Oral ,Aluminum Hydroxide ,CD8-Positive T-Lymphocytes ,Lymphocyte Activation ,lymph-node ,Young Adult ,Insulin-Secreting Cells ,Humans ,Vitamin D ,Child ,Original Research ,Autoantigen ,Immunotherapy ,Gad-alum ,Type 1 Diabetes ,Intra-lymphatic Treatment ,Lymph-node ,intra-lymphatic treatment ,C-Peptide ,Glutamate Decarboxylase ,Immunity ,Immunology in the medical area ,Injections, Intralymphatic ,Vitamins ,autoantigen ,Interleukin-10 ,Diabetes Mellitus, Type 1 ,Treatment Outcome ,Immunologi inom det medicinska området ,Immunoglobulin G ,Female ,immunotherapy ,Lymph Nodes ,Signal Transduction - Abstract
In spite of intensive treatment Type 1 diabetes leads to serious complications. Preservation of residual beta cell function makes the disease milder, facilitates treatment, prevents complications and increase survival. So far immune interventions have had limited effect, and some serious adverse events and risks. In an open pilot trial we aimed to improve efficacy of GAD-alum treatment using lymph-node administration in combination with oral vitamin D. Here we report the clinical effect and focus on biomarkers for response to treatment. Patients (n = 12) aged 12 to 24 years with recent onset of Type 1 diabetes received 4 mu g GAD-alum into lymph-node at day 30, 60, and 90, and oral Vitamin D 2000 U/d, days 1 to 120. Beta cell function was estimated by Mixed Meal Tolerance Tests. GADA, GADA subclasses, GAD(65)-induced cytokines and proliferation, and T cells markers were analyzed. The treatment was tolerable with no adverse events. Fasting C-peptide and insulin requirement remained stable at 15 months, while HbA1c was lower than baseline. Stimulated C-peptide showed no change at 6 months but declined after 15 months (81% of baseline). Eleven patients remained in partial remission (IDAAC < 9). Patients (n = 9) with better clinical outcome had reduced proportion of IgG1 and increased IgG2, IgG3, and IgG4, increased IL-10 secretion, and reduction of proliferation and CD8(+) T cells activation. Patients with poorer clinical response had higher baseline levels of GAD(65-)induced cytokines and T-cell activation, and an increased ratio of effector/central memory T cells. Intra-lymphatic GAD treatment combined with Vitamin D might preserve beta cell function and improve clinical course in T1D. Patients with less benefit have a different quality of immune response both before and after treatment. Funding Agencies|Barndiabetesfonden (Swedish Child Diabetes Foundation); Swedish Diabetes research foundation; Diamyd Medical
- Published
- 2020
44. Immune response differs between intralymphatic or subcutaneous administration of GAD‐alum in individuals with recent onset type 1 diabetes.
- Author
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Dietrich, Fabrícia, Barcenilla, Hugo, Tavira, Beatriz, Wahlberg, Jeanette, Achenbach, Peter, Ludvigsson, Johnny, and Casas, Rosaura
- Subjects
TYPE 1 diabetes ,MONONUCLEAR leukocytes ,IMMUNE response ,ANTIGEN presentation ,LYMPH nodes - Abstract
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 μg GAD‐alum into lymph nodes (LN, n = 12) or two doses 1 month apart of 20 μg subcutaneously (SC, n = 12) were studied. GADA, GADA subclasses, GAD65‐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 GAD65‐induced secretion of IL‐5, IL‐10, and TNF‐α, 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. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
45. Intralymphatic GAD-alum Injection Modulates B Cell Response and Induces Follicular Helper T Cells and PD-1+ CD8+ T Cells in Patients With Recent-Onset Type 1 Diabetes.
- Author
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Barcenilla, Hugo, Pihl, Mikael, Wahlberg, Jeanette, Ludvigsson, Johnny, and Casas, Rosaura
- Subjects
T helper cells ,TYPE 1 diabetes ,T cells ,MONONUCLEAR leukocytes ,B cells ,INTERLEUKIN-21 ,T cell receptors ,INGUINAL hernia - Abstract
Antigen-specific immunotherapy is an appealing strategy to preserve beta-cell function in type 1 diabetes, although the approach has yet to meet its therapeutic endpoint. Direct administration of autoantigen into lymph nodes has emerged as an alternative administration route that can improve the efficacy of the treatment. In the first open-label clinical trial in humans, injection of aluminum-formulated glutamic acid decarboxylase (GAD-alum) into an inguinal lymph node led to the promising preservation of C-peptide in patients with recent-onset type 1 diabetes. The treatment induced a distinct immunomodulatory effect, but the response at the cell level has not been fully characterized. Here we used mass cytometry to profile the immune landscape in peripheral blood mononuclear cells from 12 participants of the study before and after 15 months of treatment. The immunomodulatory effect of the therapy included reduction of naïve and unswitched memory B cells, increase in follicular helper T cells and expansion of PD-1+ CD69+ cells in both CD8+ and double negative T cells. In vitro stimulation with GAD
65 only affected effector CD8+ T cells in samples collected before the treatment. However, the recall response to antigen after 15 months included induction of CXCR3+ and CD11c+Tbet+ B cells, PD-1+ follicular helper T cells and exhausted-like CD8+ T cells. This study provides a deeper insight into the immunological changes associated with GAD-alum administration directly into the lymph nodes. [ABSTRACT FROM AUTHOR]- Published
- 2022
- Full Text
- View/download PDF
46. Effect of COVID‐19 pandemic on treatment of Type 1 diabetes in children
- Author
-
Ludvigsson, Johnny
- Subjects
Pediatrics ,medicine.medical_specialty ,2019-20 coronavirus outbreak ,HbA1c ,Adolescent ,Coronavirus disease 2019 (COVID-19) ,COVID19 ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Physical Distancing ,MEDLINE ,children ,Pandemic ,medicine ,Humans ,Type 1 diabetes ,telemedicine ,Pediatrics, Perinatology, and Child Health ,Child ,health care economics and organizations ,Covid‐19 ,Glycated Hemoglobin ,Sweden ,business.industry ,Brief Report ,COVID-19 ,Pediatrik ,General Medicine ,medicine.disease ,Telemedicine ,Diabetes Mellitus, Type 1 ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Regular Articles & Brief Reports ,business - Abstract
n/a Funding Agencies|Vinnova and Barndiabetesfonden (Swedish Child Diabetes Foundation)
- Published
- 2020
47. Increasing plasma glucose before the development of type 1 diabetes—the TRIGR study.
- Author
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Ludvigsson, Johnny, Cuthbertson, David, Becker, Dorothy J., Kordonouri, Olga, Aschemeier, Bärbel, Pacaud, Daniele, Clarson, Cheril, Krischer, Jeffrey P., and Knip, Mikael
- Subjects
- *
RESEARCH , *AUTOANTIBODIES , *GLYCOSYLATED hemoglobin , *INFANT formulas , *HYPERGLYCEMIA , *CLINICAL trials , *BLOOD sugar , *TYPE 1 diabetes , *MEDICAL cooperation , *BLIND experiment , *KAPLAN-Meier estimator , *DESCRIPTIVE statistics , *DATA analysis software , *FAMILY history (Medicine) - Abstract
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]
- Published
- 2021
- Full Text
- View/download PDF
48. Combined Etanercept, GAD-alum and vitamin D treatment: an open pilot trial to preserve beta cell function in recent onset type 1 diabetes.
- Author
-
Ludvigsson, Johnny, Routray, Indusmita, Vigård, Tore, Hanås, Ragnar, Rathsman, Björn, Carlsson, Annelie, Särnblad, Stefan, Albin, Anna‐Karin, Arvidsson, Carl‐Göran, Samuelsson, Ulf, Casas, Rosaura, Albin, Anna-Karin, and Arvidsson, Carl-Göran
- Subjects
TYPE 1 diabetes ,MONONUCLEAR leukocytes ,PANCREATIC beta cells ,VITAMIN D ,CELL physiology ,RICKETS - Abstract
Aim: We aimed to study the feasibility and tolerability of a combination therapy consisting of glutamic acid decarboxylase (GAD-alum), Etanercept and vitamin D in children and adolescents with newly diagnosed with type 1 diabetes (T1D), and evaluate preservation of beta cell function.Material and Methods: Etanercept Diamyd Combination Regimen is an open-labelled multi-centre study pilot trial which enrolled 20 GAD antibodies positive T1D patients (7 girls and 13 boys), aged (mean ±SD): 12.4 ± 2.3 (8.3-16.1) years, with a diabetes duration of 81.4 ± 22.1 days. Baseline fasting C-peptide was 0.24 ± 0.1 (0.10-0.35) nmol/l. The patients received Day 1-450 Vitamin D (Calciferol) 2000 U/d per os, Etanercept sc Day 1-90 0.8 mg/kg once a week and GAD-alum sc injections (20 μg, Diamyd™) Day 30 and 60. They were followed for 30 months.Results: No treatment related serious adverse events were observed. After 6 months 90-min stimulated C-peptide had improved in 8/20 patients and C-peptide area under the curve (AUC) after Mixed Meal Tolerance Test in 5 patients, but declined thereafter, while HbA1c and insulin requirement remained close to baseline. Administration of Etanercept did not reduce tumour necrosis factor (TNF) spontaneous secretion from peripheral blood mononuclear cells, but rather GAD65-induced TNF-α increased. Spontaneous interleukin-17a secretion increased after the administration of Etanercept, and GAD65-induced cytokines and chemokines were also enhanced following 1 month of Etanercept administration.Conclusions: Combination therapy with parallel treatment with GAD-alum, Etanercept and vitamin D in children and adolescents with type 1 diabetes was feasible and tolerable but had no beneficial effects on the autoimmune process or beta cell function. [ABSTRACT FROM AUTHOR]- Published
- 2021
- Full Text
- View/download PDF
49. Incidence, prevalence and clinical manifestations at onset of juvenile diabetes in Tanzania
- Author
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Jasem, D., Majaliwa, E. S., Ramaiya, K., Najem, S., Swai, A. B. M., and Ludvigsson, Johnny
- Subjects
Type 1 diabetes ,Tanzania ,Incidence ,Prevalence ,Children ,DKA ,Pediatrik ,Pediatrics - Abstract
Better knowledge on incidence, prevalence and clinical manifestations is needed for planning diabetes care in Sub Saharan Africa. Aims: To find a crude incidence/prevalence of diabetes in children and young adults in a low resource setting, classify the diabetes and audit the health record keeping. Methods: A retrospective observational study based on medical recordings 2010-2016. Target population was children and adolescent registered in Changing Diabetes in Children (CDiC) or Life for a Child (LFAC) programs for children with T1DM and diagnosed at 5 diabetes clinics in three geographical regions of Tanzania. 604 patients files were available from five hospitals. Results: 336/604 files covered patients amp;lt;15 years of age at diagnosis. The prevalence of diabetes amp;lt;15 years of age ranged from 10.1 to 11.9 per 100,000 children and the annual incidence 1.8-1.9/100,000 children, with peak incidence at 10-14 years. A lot of data were missing. The great majority of the patients presented with typical signs and symptoms of T1D, 83.7% with plausible ketoacidosis (DKA). Conclusions: Diabetes incidence and prevalence is still low. T1D seems to dominate with very high frequency of DKA at diagnosis. Increased awareness of diabetes both in health care and community is needed. (C) 2019 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
- Published
- 2019
50. Toxic metals in cord blood and later development of Type 1 diabetes
- Author
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Ludvigsson, Johnny, Andersson-White, Pär, and Guerrero-Bosagna, Carlos
- Subjects
Medicin och hälsovetenskap ,children ,ABIS ,aetiology ,toxic metals ,type 1 diabetes ,Medical and Health Sciences - Abstract
The incidence of type 1 diabetes (T1D) has increased explained by changes in environment or lifestyle. In modern society dissemination of heavy metals has increased. As the autoimmune process usually starts already, we hypothesized that exposure to toxic metals during fetal life might contribute to development of T1D in children. We analysed arsenic (AS), aluminium (Al), cadmium (Cd), lithium (Li), mercury (Hg), lead (Pb), in cord blood of 20 children who later developed T1D (probands), and in 40 age-and sex-matched controls. Analysis of heavy metals in cord blood was performed by ALS Scandinavia AB (Luleå, Sweden) using the 'ultrasensitive inductively coupled plasma sector field mass spectrometry method' (ICP-SFMS) after acid digestion with HNO3. Most children had no increased concentrations of the metals in cord blood. However, children who later developed T1D had more often increased concentrations (above limit of detection; LOD) of aluminium (p = 0.006) in cord blood than the non-diabetic controls, and also more often mercury and arsenic (n.s). Our conclusion is that exposure to toxic metals during pregnancy might be one among several contributing environmental factors to the disease process if confirmed in other birth cohort trials.
- Published
- 2019
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