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Ludvigsson, Johnny
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Long, A. E., Wilson, I. V., Becker, D. J., Libman, I. M., Arena, V. C., Wong, F. S., . . . Gillespie, K. M. (2018). Characteristics of slow progression to diabetes in multiple islet autoantibody-positive individuals from five longitudinal cohorts: the SNAIL study. Diabetologia, 61(6), 1484-1490
Öppna denna publikation i ny flik eller fönster >>Characteristics of slow progression to diabetes in multiple islet autoantibody-positive individuals from five longitudinal cohorts: the SNAIL study
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2018 (Engelska)Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, nr 6, s. 1484-1490Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Aims/hypothesis Multiple islet autoimmunity increases risk of diabetes, but not all individuals positive for two or more islet autoantibodies progress to disease within a decade. Major islet autoantibodies recognise insulin (IAA), GAD (GADA), islet antigen-2 (IA-2A) and zinc transporter 8 (ZnT8A). Here we describe the baseline characteristics of a unique cohort of slow progressors (n = 132) who were positive for multiple islet autoantibodies (IAA, GADA, IA-2A or ZnT8A) but did not progress to diabetes within 10 years. Methods Individuals were identified from five studies (BABYDIAB, Germany; Diabetes Autoimmunity Study in the Young [DAISY], USA; All Babies in Southeast Sweden [ABIS], Sweden; Barts Oxford Family Study [BOX], UK and the Pittsburgh Family Study, USA). Multiple islet autoantibody characteristics were determined using harmonised assays where possible. HLA class II risk was compared between slow progressors and rapid progressors (n = 348 diagnosed amp;lt; 5 years old from BOX) using the chi(2) test. Results In the first available samples with detectable multiple antibodies, the most frequent autoantibodies were GADA (92%), followed by ZnT8A (62%), IAA (59%) and IA-2A (41%). High risk HLA class II genotypes were less frequent in slow (28%) than rapid progressors (42%, p = 0.011), but only two slow progressors carried the protective HLA DQ6 allele. Conclusion No distinguishing characteristics of slow progressors at first detection of multiple antibodies have yet been identified. Continued investigation of these individuals may provide insights into slow progression that will inform future efforts to slow or prevent progression to clinical diabetes.

Ort, förlag, år, upplaga, sidor
SPRINGER, 2018
Nyckelord
HLA class II; Islet autoantibodies; Slow progression; Type 1 diabetes
Nationell ämneskategori
Endokrinologi och diabetes
Identifikatorer
urn:nbn:se:liu:diva-147895 (URN)10.1007/s00125-018-4591-5 (DOI)000431650800024 ()29532109 (PubMedID)
Anmärkning

Funding Agencies|Diabetes UK-Fulbright Award; Diabetes UK Moffat Travelling Fellowship [13/0004636]; Diabetes UK [14/0004869]; JDRF [17-2013-529, 17-2013-535]; Deutsche Forschungsgemeinschaft (DFG) [ZI-310/14-1]; National Institutes of Health (NIH) [R01 DK32083, DK32493]; Vetenskapsradet; Novo Nordisk; Barndiabetesfonden; ALF grants; Region Ostergotland and Medical Research Council of southeast Sweden (Forskningsradet i sydostrasverige, FORSS) [12594]; NIH [R01 DK53456, DK56200, R01 DK24021]; NIDDK [PA-04-081]; Brehm Coalition by the University of Michigan Center for Computational Medicine and Biology Pilot Research Program NIH Grant [R01 DK46864]; General Clinical Research Center of the Childrens Hospital of Pittsburgh Grant [MO1 RR 00084]; Renziehausen fund

Tillgänglig från: 2018-05-23 Skapad: 2018-05-23 Senast uppdaterad: 2019-05-01
Knip, M., Akerblom, H. K., Al Taji, E., Becker, D., Bruining, J., Castano, L., . . . Wasikowa, R. (2018). Effect of Hydrolyzed Infant Formula vs Conventional Formula on Risk of Type 1 Diabetes The TRIGR Randomized Clinical Trial. Journal of the American Medical Association (JAMA), 319(1), 38-48
Öppna denna publikation i ny flik eller fönster >>Effect of Hydrolyzed Infant Formula vs Conventional Formula on Risk of Type 1 Diabetes The TRIGR Randomized Clinical Trial
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2018 (Engelska)Ingår i: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 319, nr 1, s. 38-48Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

IMPORTANCE Early exposure to complex dietary proteins may increase the risk of type 1 diabetes in children with genetic disease susceptibility. There are no intact proteins in extensively hydrolyzed formulas. OBJECTIVE To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of type 1 diabetes in young children. DESIGN, SETTING, AND PARTICIPANTS An international double-blind randomized clinical trial of 2159 infants with human leukocyte antigen-conferred disease susceptibility and a first-degree relative with type 1 diabetes recruited from May 2002 to January 2007 in 78 study centers in 15 countries; 1081 were randomized to be weaned to the extensively hydrolyzed casein formula and 1078 to a conventional formula. The follow-up of the participants ended on February 28, 2017. INTERVENTIONS The participants received either a casein hydrolysate or a conventional adapted cows milk formula supplemented with 20% of the casein hydrolysate. The minimum duration of study formula exposure was 60 days by 6 to 8 months of age. MAIN OUTCOMES AND MEASURES Primary outcome was type 1 diabetes diagnosed according to World Health Organization criteria. Secondary outcomes included age at diabetes diagnosis and safety (adverse events). RESULTS Among 2159 newborn infants (1021 female [47.3%]) who were randomized, 1744 (80.8%) completed the trial. The participants were observed for a median of 11.5 years (quartile [Q] 1-Q3, 10.2-12.8). The absolute risk of type 1 diabetes was 8.4% among those randomized to the casein hydrolysate (n = 91) vs 7.6% among those randomized to the conventional formula (n = 82) (difference, 0.8%[95% CI, -1.6% to 3.2%]). The hazard ratio for type 1 diabetes adjusted for human leukocyte antigen risk group, duration of breastfeeding, duration of study formula consumption, sex, and region while treating study center as a random effect was 1.1 (95% CI, 0.8 to 1.5; P = .46). The median age at diagnosis of type 1 diabetes was similar in the 2 groups (6.0 years [Q1-Q3, 3.1-8.9] vs 5.8 years [Q1-Q3, 2.6-9.1]; difference, 0.2 years [95% CI, -0.9 to 1.2]). Upper respiratory infections were the most common adverse event reported (frequency, 0.48 events/year in the hydrolysate group and 0.50 events/year in the control group). CONCLUSIONS AND RELEVANCE Among infants at risk for type 1 diabetes, weaning to a hydrolyzed formula compared with a conventional formula did not reduce the cumulative incidence of type 1 diabetes after median follow-up for 11.5 years. These findings do not support a need to revise the dietary recommendations for infants at risk for type 1 diabetes.

Ort, förlag, år, upplaga, sidor
AMER MEDICAL ASSOC, 2018
Nationell ämneskategori
Endokrinologi och diabetes
Identifikatorer
urn:nbn:se:liu:diva-144246 (URN)10.1001/jama.2017.19826 (DOI)000419116000014 ()29297078 (PubMedID)
Anmärkning

Funding Agencies|Eunice Kennedy Shriver National Institute of Child Health and Development (NICHD); National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health [HD040364, HD042444, HD051997]; Canadian Institutes of Health Research; Commission of the European Communities [QLK1-2002-00372]; European Foundation for the Study of Diabates/JDRF/Novo Nordisk; Academy of Finland (Centre of Excellence in Molecular Systems Immunology and Physiology Research) [250114]; Dutch Diabetes Research Foundation; Finnish Diabetes Research Foundation; JDRF

Tillgänglig från: 2018-01-22 Skapad: 2018-01-22 Senast uppdaterad: 2019-05-01
Simona Chisalita, I. & Ludvigsson, J. (2018). Insulin-Like Growth Factor-1 at Diagnosis and during Subsequent Years in Adolescents with Type 1 Diabetes. Journal of Diabetes Research, Article ID 8623560.
Öppna denna publikation i ny flik eller fönster >>Insulin-Like Growth Factor-1 at Diagnosis and during Subsequent Years in Adolescents with Type 1 Diabetes
2018 (Engelska)Ingår i: Journal of Diabetes Research, ISSN 2314-6745, E-ISSN 2314-6753, artikel-id 8623560Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Background. Type 1 diabetes (T1D) in adolescents is associated with alterations in the insulin-like factor system probably caused both by a deranged metabolism and insulinopenia in the portal vein.

Objective. To study how the circulating IGF-1 is affected at diagnosis and during subsequent years in adolescents with T1D.

Methods. Ten girls and ten boys with type 1 diabetes (T1D), aged 13.0 +/- 1.4 (mean +/- SD) years at diagnosis, took part in the study. Blood samples were drawn at diagnosis and after 3, 9, 18, and 48 months. HbA1c, total IGF-1, and C-peptide were measured.

Results. At diagnosis, the patients had high HbA1c, low IGF-1, and measurable C-peptide. After the start of insulin treatment, maximal improvement in glycemic control and IGF-1 occurred within 3 months and then both tended to deteriorate, that is, HbA1c to increase and IGF-1 to decrease. C-peptide decreased with time, and after 4 years, half of the patients were C-peptide negative. At diagnosis, C-peptide correlated positively to IGF-1 (r = 0 50; p amp;lt; 0 03). C-peptide correlated negatively with insulin dose (U/kg) after 18 and 48 months from diagnosis (r = -0 48; p amp;lt; 0 03 and r = -0 72; p amp;lt; 0 001, resp.).

Conclusions. In conclusion, our results show that in newly diagnosed adolescents with type 1 diabetes and deranged metabolism, the IGF-1 level is low and rapidly improves with insulin treatment but later tends to decrease concomitantly with declining endogenous insulin secretion.

Ort, förlag, år, upplaga, sidor
Hindawi Publishing Corporation, 2018
Nationell ämneskategori
Endokrinologi och diabetes
Identifikatorer
urn:nbn:se:liu:diva-147455 (URN)10.1155/2018/8623560 (DOI)000428896300001 ()29744370 (PubMedID)
Anmärkning

Funding Agencies|Landstinget Ostergotland; Swedish Medical Research Council [04952]

Tillgänglig från: 2018-05-16 Skapad: 2018-05-16 Senast uppdaterad: 2019-02-28Bibliografiskt granskad
Ludvigsson, J., Lefebvre, P. & Nerup, J. (2018). It is time to restore Rules for Authorship of scientific publications [Letter to the editor]. Pediatric Diabetes, 19(3), 586-586
Öppna denna publikation i ny flik eller fönster >>It is time to restore Rules for Authorship of scientific publications
2018 (Engelska)Ingår i: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 19, nr 3, s. 586-586Artikel i tidskrift, Letter (Övrigt vetenskapligt) Published
Abstract [en]

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Ort, förlag, år, upplaga, sidor
WILEY, 2018
Nyckelord
authorship; fraud in research; research ethics
Nationell ämneskategori
Endokrinologi och diabetes
Identifikatorer
urn:nbn:se:liu:diva-147920 (URN)10.1111/pedi.12572 (DOI)000430921600036 ()28994232 (PubMedID)2-s2.0-85045886791 (Scopus ID)
Tillgänglig från: 2018-05-23 Skapad: 2018-05-23 Senast uppdaterad: 2019-05-01Bibliografiskt granskad
Ludvigsson, J. (2018). Nej – barn med typ 1-diabetes lever inte i ständig livsfara. Läkartidningen, 115
Öppna denna publikation i ny flik eller fönster >>Nej – barn med typ 1-diabetes lever inte i ständig livsfara
2018 (Svenska)Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 115Artikel i tidskrift, Editorial material (Övrigt vetenskapligt) Published
Ort, förlag, år, upplaga, sidor
Stockholm, Sweden: Läkartidningen Förlag AB, 2018
Nationell ämneskategori
Endokrinologi och diabetes
Identifikatorer
urn:nbn:se:liu:diva-156937 (URN)30536231 (PubMedID)
Tillgänglig från: 2019-05-15 Skapad: 2019-05-15 Senast uppdaterad: 2019-06-14Bibliografiskt granskad
Åkerman, L., Casas, R., Ludvigsson, J., Tavira Iglesias, B. & Skoglund, C. (2018). Serum miRNA levels are related to glucose homeostasis and islet autoantibodies in children with high risk for type 1 diabetes. PLoS ONE, 13(1), Article ID e0191067.
Öppna denna publikation i ny flik eller fönster >>Serum miRNA levels are related to glucose homeostasis and islet autoantibodies in children with high risk for type 1 diabetes
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2018 (Engelska)Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, nr 1, artikel-id e0191067Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Micro RNAs (miRNAs) are promising disease biomarkers due to their high stability. Their expression in serum is altered in type 1 diabetes, but whether deviations exist in individuals with high risk for type 1 diabetes remains unexplored. We therefore assessed serum miRNAs in high-risk individuals (n = 21) positive for multiple islet autoantibodies, age-matched healthy children (n = 17) and recent-onset type 1 diabetes patients (n = 8), using Serum/Plasma Focus microRNA PCR Panels from Exiqon. The miRNA levels in the high-risk group were similar to healthy controls, and no specific miRNA profile was identified for the high-risk group. However, serum miRNAs appeared to reflect glycemic status and ongoing islet auto-immunity in high-risk individuals, since several miRNAs were associated to glucose homeostasis and autoantibody titers. High-risk individuals progressing to clinical disease after the sampling could not be clearly distinguished from non-progressors, while miRNA expression in the type 1 diabetes group deviated significantly from high-risk individuals and healthy controls, perhaps explained by major metabolic disturbances around the time of diagnosis.

Ort, förlag, år, upplaga, sidor
PUBLIC LIBRARY SCIENCE, 2018
Nationell ämneskategori
Endokrinologi och diabetes
Identifikatorer
urn:nbn:se:liu:diva-145142 (URN)10.1371/journal.pone.0191067 (DOI)000422749500025 ()29346396 (PubMedID)
Anmärkning

Funding Agencies|Swedish Child Diabetes Foundation (Barndiabetesfonden); Swedish Research Council (Vetenskapsradet); Medical Research Council of Southeast Sweden (Forskningsradet i sydostra sverige, FORSS); Novo Nordisk Foundation; ALF/County Council of Ostergotland

Tillgänglig från: 2018-02-13 Skapad: 2018-02-13 Senast uppdaterad: 2019-05-21
Ludvigsson, J. (2018). Vi måste bli bättre på att diagnostisera typ 1-diabetes [Diagnostics of type 1 diabetes must be improved]. Läkartidningen, 115
Öppna denna publikation i ny flik eller fönster >>Vi måste bli bättre på att diagnostisera typ 1-diabetes [Diagnostics of type 1 diabetes must be improved]
2018 (Svenska)Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 115Artikel i tidskrift, Editorial material (Övrigt vetenskapligt) Published
Abstract [sv]

Incidence of type 1 diabetes in children and adolescents continues to increase but diagnosis is often delayed and keto-acidosis too common. More information is needed. General auto-antibody screening can be discussed.

Ort, förlag, år, upplaga, sidor
Stockholm, Sweden: Läkartidningen Förlag AB, 2018
Nationell ämneskategori
Endokrinologi och diabetes
Identifikatorer
urn:nbn:se:liu:diva-156942 (URN)29381176 (PubMedID)
Tillgänglig från: 2019-05-15 Skapad: 2019-05-15 Senast uppdaterad: 2019-06-14Bibliografiskt granskad
Ludvigsson, J. (2017). Etiken måste få väga tyngre än juridiken vid sena aborter [Ethics must be more important than the law in late abortions].. Läkartidningen, 114
Öppna denna publikation i ny flik eller fönster >>Etiken måste få väga tyngre än juridiken vid sena aborter [Ethics must be more important than the law in late abortions].
2017 (Svenska)Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 114Artikel i tidskrift, Editorial material (Övrigt vetenskapligt) Published
Ort, förlag, år, upplaga, sidor
Stockholm, Sweden: Läkartidningen Förlag AB, 2017
Nationell ämneskategori
Endokrinologi och diabetes
Identifikatorer
urn:nbn:se:liu:diva-156938 (URN)28829485 (PubMedID)
Tillgänglig från: 2019-05-15 Skapad: 2019-05-15 Senast uppdaterad: 2019-06-14Bibliografiskt granskad
Beam, C. A., MacCallum, C., Herold, K. C., Wherrett, D. K., Palmer, J. & Ludvigsson, J. (2017). GAD vaccine reduces insulin loss in recently diagnosed type 1 diabetes: findings from a Bayesian meta-analysis. Diabetologia, 60(1), 43-49
Öppna denna publikation i ny flik eller fönster >>GAD vaccine reduces insulin loss in recently diagnosed type 1 diabetes: findings from a Bayesian meta-analysis
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2017 (Engelska)Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 60, nr 1, s. 43-49Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

GAD is a major target of the autoimmune response that occurs in type 1 diabetes mellitus. Randomised controlled clinical trials of a GAD + alum vaccine in human participants have so far given conflicting results. In this study, we sought to see whether a clearer answer to the question of whether GAD65 has an effect on C-peptide could be reached by combining individual-level data from the randomised controlled trials using Bayesian meta-analysis to estimate the probability of a positive biological effect (a reduction in C-peptide loss compared with placebo approximately 1 year after the GAD vaccine). We estimate that there is a 98% probability that 20 mu g GAD with alum administered twice yields a positive biological effect. The effect is probably a 15-20% reduction in the loss of C-peptide at approximately 1 year after treatment. This translates to an annual expected loss of between -0.250 and -0.235 pmol/ml in treated patients compared with an expected 2 h AUC loss of -0.294 pmol/ml at 1 year for untreated newly diagnosed patients. The biological effect of this vaccination should be developed further in order to reach clinically desirable reductions in insulin loss in patients recently diagnosed with type 1 diabetes.

Ort, förlag, år, upplaga, sidor
SPRINGER, 2017
Nyckelord
Bayes methods; Glutamic acid decarboxylase (GAD); Meta-analysis; Type 1 diabetes; Vaccine
Nationell ämneskategori
Endokrinologi och diabetes
Identifikatorer
urn:nbn:se:liu:diva-133724 (URN)10.1007/s00125-016-4122-1 (DOI)000389634000007 ()27704166 (PubMedID)
Anmärkning

Funding Agencies|JDRF [1-INO-20140170-A-V]

Tillgänglig från: 2017-01-11 Skapad: 2017-01-09 Senast uppdaterad: 2018-05-02
Klingberg, S., Ludvigsson, J. & Brekke, H. K. (2017). Introduction of complementary foods in Sweden and impact of maternal education on feeding practices.. Public Health Nutrition, 20(6), 1054-1062
Öppna denna publikation i ny flik eller fönster >>Introduction of complementary foods in Sweden and impact of maternal education on feeding practices.
2017 (Engelska)Ingår i: Public Health Nutrition, ISSN 1368-9800, E-ISSN 1475-2727, Vol. 20, nr 6, s. 1054-1062Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

OBJECTIVE: To describe the introduction of complementary foods in a population-based cohort in relation to recommendations and explore the possible impact of maternal education on infant feeding practices.

DESIGN: Prospective data from the All Babies in Southeast Sweden (ABIS) cohort study were used. The ABIS study invited all infants born in south-east Sweden during October 1997-October 1999 (n 21 700) to participate. A questionnaire was completed for 16 022 infants. During the infants' first year parents continuously filed in a diary covering introduction of foods.

SETTING: Sweden.

SUBJECTS: Infants (n 9727) with completed food diaries.

RESULTS: Potatoes, vegetables, fruits/berries and porridge were the foods first introduced, with a median introduction between 19 and 22 weeks, followed by introduction of meat, cow's milk, follow-on formula and sour milk/yoghurt between 24 and 27 weeks. Early introduction of any food, before 16 weeks, occurred for 27 % of the infants and was more common in infants of mothers with low education. Overall, potatoes (14·7 %), vegetables (11·1 %), fruits/berries (8·5 %), porridge (7·4 %) and follow-on formula (2·7 %) were the foods most frequently introduced early. The majority of infants (≥70 %) were introduced to potatoes, vegetables, fruits/berries and porridge during concurrent breast-feeding, but introduction during concurrent breast-feeding was less common in infants of mothers with low education.

CONCLUSIONS: Most infants were introduced to complementary foods timely in relation to recommendations. Low maternal education was associated with earlier introduction of complementary foods and less introduction during concurrent breast-feeding. Still, the results indicated exposure to fewer foods at 12 months in infants of mothers with low education.

Ort, förlag, år, upplaga, sidor
John Wiley & Sons, 2017
Nationell ämneskategori
Hälsovetenskaper
Identifikatorer
urn:nbn:se:liu:diva-134865 (URN)10.1017/S1368980016003104 (DOI)000399398300011 ()27917749 (PubMedID)
Anmärkning

Funding agencies: Swedish Child Diabetes Foundation (Barndiabetesfonden); Novo Nordisk Foundation; Research Council of Southeast Sweden (FORSS); Swedish Research Council [K2005-72X-11242-11A]; ALF/County Council of Ostergotland

Tillgänglig från: 2017-02-27 Skapad: 2017-02-27 Senast uppdaterad: 2018-05-02Bibliografiskt granskad
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