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Ludvigsson, Johnny
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Publications (10 of 355) Show all publications
Rewers, M. & Ludvigsson, J. (2016). Environmental risk factors for type 1 diabetes. The Lancet, 387(10035), 2340-2348.
Open this publication in new window or tab >>Environmental risk factors for type 1 diabetes
2016 (English)In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 387, no 10035, 2340-2348 p.Article, review/survey (Refereed) Published
Abstract [en]

The incidence of type 1 diabetes has risen considerably in the past 30 years due to changes in the environment that have been only partially identified. In this Series paper, we critically discuss candidate triggers of islet autoimmunity and factors thought to promote progression from autoimmunity to overt type 1 diabetes. We revisit previously proposed hypotheses to explain the growth in the incidence of type 1 diabetes in light of current data. Finally, we suggest a unified model in which immune tolerance to beta cells can be broken by several environmental exposures that induce generation of hybrid peptides acting as neoautoantigens.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE INC, 2016
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:liu:diva-129471 (URN)10.1016/S0140-6736(16)30507-4 (DOI)000376969100037 ()
Note

Funding Agencies|National Institutes of Health [DK32493]; Juvenile Diabetes Research Foundation [17-2013-535]; Swedish Child Diabetes Foundation (Barndiabetesfonden); JDF-Wallenberg [K98-99JD-12813-01A]; Swedish Medical Research Council (MFR) [K99-72X-11242-05A]; Research Council of Southeast Sweden

Available from: 2016-06-21 Created: 2016-06-20 Last updated: 2017-06-09
Carlsson, E., Ludvigsson, J., Huus, K. & Faresjö, M. (2016). High physical activity in young children suggests positive effects by altering autoantigen-induced immune activity. Scandinavian Journal of Medicine and Science in Sports, 26(4), 441-450.
Open this publication in new window or tab >>High physical activity in young children suggests positive effects by altering autoantigen-induced immune activity
2016 (English)In: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, E-ISSN 1600-0838, Vol. 26, no 4, 441-450 p.Article in journal (Refereed) Published
Abstract [en]

Physical activity in children is associated with several positive health outcomes such as decreased cardiovascular risk factors, improved lung function, enhanced motor skill development, healthier body composition, and also improved defense against inflammatory diseases. We examined how high physical activity vs a sedentary lifestyle in young children influences the immune response with focus on autoimmunity. Peripheral blood mononuclear cells, collected from 55 5-year-old children with either high physical activity (n = 14), average physical activity (n = 27), or low physical activity (n = 14), from the All Babies In Southeast Sweden (ABIS) cohort, were stimulated with antigens (tetanus toxoid and beta-lactoglobulin) and autoantigens (GAD65 , insulin, HSP60, and IA-2). Immune markers (cytokines and chemokines), C-peptide and proinsulin were analyzed. Children with high physical activity showed decreased immune activity toward the autoantigens GAD65 (IL-5, P < 0.05), HSP60 and IA-2 (IL-10, P < 0.05) and also low spontaneous pro-inflammatory immune activity (IL-6, IL-13, IFN-γ, TNF-α, and CCL2 (P < 0.05)) compared with children with an average or low physical activity. High physical activity in young children seems to have positive effects on the immune system by altering autoantigen-induced immune activity.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2016
Keyword
Physical activity, Autoimmunity, Cytokines. Immune response, Young children
National Category
Physiotherapy Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:liu:diva-126414 (URN)10.1111/sms.12450 (DOI)000373356600009 ()25892449 (PubMedID)
Note

Funding agencies:  Swedish Council for Working Life and Social Research [2008-0284]; Swedish Research Council [K2009-70X-21086-01-3]; Medical Research Council of Southeast Sweden; Swedish Child Diabetes Foundation; Academy for Health and Care Jonkoping County Council

Available from: 2016-03-23 Created: 2016-03-23 Last updated: 2017-11-30Bibliographically approved
Ruiz, M., Goldblatt, P., Morrison, J., Porta, D., Forastiere, F., Hryhorczuk, D., . . . Pikhart, H. (2016). Impact of Low Maternal Education on Early Childhood Overweight and Obesity in Europe. Paediatric and Perinatal Epidemiology, 30(3), 274-284.
Open this publication in new window or tab >>Impact of Low Maternal Education on Early Childhood Overweight and Obesity in Europe
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2016 (English)In: Paediatric and Perinatal Epidemiology, ISSN 0269-5022, E-ISSN 1365-3016, Vol. 30, no 3, 274-284 p.Article in journal (Refereed) Published
Abstract [en]

BackgroundComparable evidence on adiposity inequalities in early life is lacking across a range of European countries. This study investigates whether low maternal education is associated with overweight and obesity risk in children from distinct European settings during early childhood. MethodsProspective data of 45 413 children from 11 European cohorts were used. Childrens height and weight obtained at ages 4-7 years were used to assess prevalent overweight and obesity according to the International Obesity Task Force definition. The Relative/Slope Indices of Inequality (RII/SII) were estimated within each cohort and by gender to investigate adiposity risk among children born to mothers with low education as compared to counterparts born to mothers with high education. Individual-data meta-analyses were conducted to obtain aggregate estimates and to assess heterogeneity between cohorts. ResultsLow maternal education yielded a substantial risk of early childhood adiposity across 11 European countries. Low maternal education yielded a mean risk ratio of 1.58 (95% confidence interval (CI) 1.34, 1.85) and a mean risk difference of 7.78% (5.34, 10.22) in early childhood overweight, respectively, measured by the RII and SII. Early childhood obesity risk by low maternal education was as substantial for all cohorts combined (RII = 2.61 (2.10, 3.23)) and (SII = 4.01% (3.14, 4.88)). Inequalities in early childhood adiposity were consistent among boys, but varied among girls in a few cohorts. ConclusionsConsiderable inequalities in overweight and obesity are evident among European children in early life. Tackling early childhood adiposity is necessary to promote childrens immediate health and well-being and throughout the life course.

Place, publisher, year, edition, pages
WILEY-BLACKWELL, 2016
Keyword
child; preschool; child development; cohort studies; comparative study; Czech Republic; epidemiology; Europe; Finland; France; Greece; health inequalities; Italy; maternal educational status; meta-analysis; Netherlands; obesity; overweight; Portugal; Spain; Sweden; United Kingdom; Ukraine
National Category
Clinical Medicine Basic Medicine
Identifiers
urn:nbn:se:liu:diva-127547 (URN)10.1111/ppe.12285 (DOI)000373623800008 ()26945670 (PubMedID)
Note

Funding Agencies|European Union [278350]; Ministry of Education of the Czech Republic [LM2011028, LO1214]; Grant Agency of the Masaryk University [MUNI/M/1075/2013]; Academy of Finland; Biocenter, University of Oulu, Finland; European Commission (EUROBLCS) [QLG1-CT-2000-01643]; EU [EurHEALTHAgeing-277849]; Medical Research Council, UK (PrevMetSyn/SALVE); MRC; Netherlands Organization for Health Research and Development (ZonMw) [40-00812-98-11010]; Juvenile Diabetes Research Foundation; Swedish Child Diabetes Foundation; Research Council of Southeast Sweden

Available from: 2016-05-04 Created: 2016-05-03 Last updated: 2018-01-10
Ludvigsson, J. (2016). Letter: Authors Reply to Dayal: "Therapies to Preserve beta-Cell Function in Type 1 Diabetes in DRUGS, vol 76, issue 5, pp 627-627 [Letter to the editor]. Drugs, 76(5), 627-627.
Open this publication in new window or tab >>Letter: Authors Reply to Dayal: "Therapies to Preserve beta-Cell Function in Type 1 Diabetes in DRUGS, vol 76, issue 5, pp 627-627
2016 (English)In: Drugs, ISSN 0012-6667, E-ISSN 1179-1950, Vol. 76, no 5, 627-627 p.Article in journal, Letter (Other academic) Published
Abstract [en]

n/a

Place, publisher, year, edition, pages
ADIS INT LTD, 2016
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-128752 (URN)10.1007/s40265-016-0561-8 (DOI)000375052300009 ()26979969 (PubMedID)
Available from: 2016-05-31 Created: 2016-05-30 Last updated: 2017-11-30
Ping Zhao, L., Alshiekh, S., Zhao, M., Carlsson, A., Elding Larsson, H., Forsander, G., . . . Lernmark, A. (2016). Next-Generation Sequencing Reveals That HLA-DRB3, -DRB4, and -DRB5 May Be Associated With Islet Autoantibodies and Risk for Childhood Type 1 Diabetes. Diabetes, 65(3), 710-718.
Open this publication in new window or tab >>Next-Generation Sequencing Reveals That HLA-DRB3, -DRB4, and -DRB5 May Be Associated With Islet Autoantibodies and Risk for Childhood Type 1 Diabetes
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2016 (English)In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 65, no 3, 710-718 p.Article in journal (Refereed) Published
Abstract [en]

The possible contribution of HLA-DRB3, -DRB4, and -DRB5 alleles to type 1 diabetes risk and to insulin autoantibody (IAA), GAD65 (GAD autoantibody [GADA]), IA-2 antigen (IA-2A), or ZnT8 against either of the three amino acid variants R, W, or Q at position 325 (ZnT8RA, ZnT8WA, and ZnT8QA, respectively) at clinical diagnosis is unclear. Next-generation sequencing (NGS) was used to determine all DRB alleles in consecutively diagnosed patients ages 1-18 years with islet autoantibody-positive type 1 diabetes (n = 970) and control subjects (n = 448). DRB3, DRB4, or DRB5 alleles were tested for an association with the risk of DRB1 for autoantibodies, type 1 diabetes, or both. The association between type 1 diabetes and DRB1*03:01:01 was affected by DRB3*01:01:02 and DRB3*02:02:01. These DRB3 alleles were associated positively with GADA but negatively with ZnT8WA, IA-2A, and IAA. The negative association between type 1 diabetes and DRB1*13:01:01 was affected by DRB3*01:01:02 to increase the risk and by DRB3*02:02:01 to maintain a negative association. DRB4*01:03:01 was strongly associated with type 1 diabetes (P = 10(-36)), yet its association was extensively affected by DRB1 alleles from protective (DRB1*04:03:01) to high (DRB1*04:01:01) risk, but its association with DRB1*04:05:01 decreased the risk. HLA-DRB3, -DRB4, and -DRB5 affect type 1 diabetes risk and islet autoantibodies. HLA typing with NGS should prove useful to select participants for prevention or intervention trials.

Place, publisher, year, edition, pages
AMER DIABETES ASSOC, 2016
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-126246 (URN)10.2337/db15-1115 (DOI)000370961000024 ()26740600 (PubMedID)
Note

Funding Agencies|European Foundation for the Study of Diabetes Clinical Research Grants Programme; Swedish Child Diabetes Foundation; National Institutes of Health [DK-63861, DK-26190]; Swedish Research Council; Linne grant; Skane County Council for Research and Development; Swedish Association of Local Authorities and Regions; Knut and Alice Wallenberg Foundation

Available from: 2016-03-21 Created: 2016-03-21 Last updated: 2017-11-30
Granfors, M., Augustin, H., Ludvigsson, J. & Brekke, H. K. (2016). No association between use of multivitamin supplement containing vitamin D during pregnancy and risk of Type 1 Diabetes in the child. Pediatric Diabetes, 17(7), 525-530.
Open this publication in new window or tab >>No association between use of multivitamin supplement containing vitamin D during pregnancy and risk of Type 1 Diabetes in the child
2016 (English)In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 17, no 7, 525-530 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND:

Sweden has the second highest incidence of type 1 diabetes in the world. Nutritional aspects in utero and in infancy affect the development. We conducted a survey to determine whether reported maternal use of vitamin D-containing micronutrient supplements during pregnancy was associated with the risk of developing type 1 diabetes in the child.

METHODS:

This report was based on data from the ABIS (All Babies In Southeast Sweden) study, with questionnaire data on 16 339 mother and infant pairs at birth and at 1-yr of age (n = 10 879), of whom 108 children were registered with type 1 diabetes before 14-16 yr of age. The questions 'during pregnancy, did you take any vitamin/mineral supplements?' and 'if yes, which? (open answer)' in addition to other lifestyle questions were answered. Logistic regression was performed with onset of type 1 diabetes as the dependent variable and vitamin D supplementation use as the independent variable, adjusted for relevant factors.

RESULTS:

Vitamin D supplementation during pregnancy was consumed by 9.3% of mothers whose children later got type1 diabetes and among 11.3% of those mothers whose children did not get type 1 diabetes (p = 0.532). No significant association was found between reported supplement intake of vitamin D during pregnancy and risk of type 1 diabetes, even when adjusting for factors which could influence the association.

CONCLUSION:

Maternal use of vitamin D-containing multivitamin supplements during pregnancy was not related to the risk of developing type 1 diabetes in children before 14-16 yr of age in Southeast of Sweden.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2016
Keyword
Child, Micronutrient, Pregnancy, Supplementation, Type 1 diabetes, Vitamin D
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:liu:diva-126408 (URN)10.1111/pedi.12334 (DOI)000388303400008 ()26552946 (PubMedID)
Note

Funding agencies: Juvenile Diabetes Research Foundation; International-Wallenberg Foundations [K 98-99D-12813-01A]; Swedish Medical Research Council [K99-72X- 11242-05A]; Swedish Child Diabetes Foundation (Barndiabetesfonden); Swedish Diabetes Association; Swedish Diary As

Available from: 2016-03-23 Created: 2016-03-23 Last updated: 2017-11-30Bibliographically approved
Jennersjö, P., Ludvigsson, J., Länne, T., Nyström, F. H. & Östgren, C. J. (2016). Pedometer-determined physical activity level and change in arterial stiffness in Type 2 diabetes over 4 years. Diabetic Medicine, 33(7), 992-997.
Open this publication in new window or tab >>Pedometer-determined physical activity level and change in arterial stiffness in Type 2 diabetes over 4 years
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2016 (English)In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 33, no 7, 992-997 p.Article in journal (Refereed) Published
Abstract [en]

Aim To explore prospectively the correlation between the level of pedometer-determined physical activity at the start of the study and the change in pulse wave velocity from baseline to 4 years later in people with Type 2 diabetes.

Methods We analysed data from 135 men and 53 women with Type 2 diabetes, aged 54–66 years. Physical activity was measured with waist-mounted pedometers on 3 consecutive days and the numbers of steps/day at baseline were classified into four groups: <5000 steps/day, 5000–7499 steps/day, 7500–9999 steps/day and ≥10 000 steps/day. Pulse wave velocity was measured using applanation tonometry over the carotid and femoral arteries at baseline and after 4 years.

Results The mean (±sd; range) number of steps/day was 8022 (±3765; 956–20 921). The participants with the lowest level of physical activity had a more pronounced increase in the change in pulse wave velocity compared with the participants with the highest. When change in pulse wave velocity was analysed as a continuous variable and adjusted for sex, age, diabetes duration, HbA1c, BMI, systolic blood pressure, pulse wave velocity at baseline, β-blocker use, statin use, unemployment, smoking and diabetes medication, the number of steps/day at baseline was significantly associated with a less steep increase in change in pulse wave velocity (P=0.005). Every 1000 extra steps at baseline corresponded to a lower increase in change in pulse wave velocity of 0.103 m/s.

Conclusions We found that a high level of pedometer-determined physical activity was associated with a slower progression of arterial stiffness over 4 years in middle-aged people with Type 2 diabetes.

Place, publisher, year, edition, pages
John Wiley & Sons, 2016
National Category
Endocrinology and Diabetes General Practice Geriatrics Sport and Fitness Sciences Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:liu:diva-125910 (URN)10.1111/dme.12873 (DOI)000379930900018 ()26227869 (PubMedID)
Note

Funding agencies: Medical Research Council of Southeast Sweden; Centre for Medical Image Science and Visualization (CMIV), Linkoping University; GE Healthcare; Swedish Heart-Lung Foundation; Swedish Research Council [12661]; King Gustaf V and Queen Victoria Freemason Found

Available from: 2016-03-08 Created: 2016-03-08 Last updated: 2018-01-10Bibliographically approved
Huus, K., Åkerman, L., Raustorp, A. & Ludvigsson, J. (2016). Physical Activity, Blood Glucose and C-Peptide in Healthy School-Children, a Longitudinal Study. PLoS ONE, 11(6), e0156401.
Open this publication in new window or tab >>Physical Activity, Blood Glucose and C-Peptide in Healthy School-Children, a Longitudinal Study
2016 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 6, e0156401- p.Article in journal (Refereed) Published
Abstract [en]

Aim To further elucidate the relationship between physical activity and several risk factors for development of diabetes (glucose, C-peptide and obesity) over time. Methods A prospective longitudinal study where physical activity was measured on 199 children from Kalmar and Linkoping at age 8, and the same 107 children from Linkoping again at age 12. Anthropometric data was collected and blood was analyzed for C-peptide and f-glucose. The children in the study were representative for the general Swedish child population, and on an average lean. Results High physical activity was related to lower C-peptide at age 8 and 12. This correlation was especially pronounced in boys, who also were more physically active than girls at both time points. The association seen at 8 years of age was similar at age 12 in most children. Children with higher BMI Z-Score had a higher fasting C-peptide (age 12) but linear regression showed that children with more steps per day were less likely to have a higher fasting C-peptide irrespective of BMI. Longitudinal follow-up showed that a decrease in physical activity increased insulin resistance and beta-cell load. Conclusions Already in young children, physical activity improves insulin sensitivity and decreases the need of C-peptide over time. This seems to become even more pronounced with increasing age when children are followed longitudinally. Low physical activity increases the load on insulin producing beta-cells, might increase the risk for both type 1- and 2 diabetes.

Place, publisher, year, edition, pages
PUBLIC LIBRARY SCIENCE, 2016
National Category
Pediatrics
Identifiers
urn:nbn:se:liu:diva-130132 (URN)10.1371/journal.pone.0156401 (DOI)000377561000012 ()27270732 (PubMedID)
Note

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

Available from: 2016-07-12 Created: 2016-07-11 Last updated: 2017-11-28
Ljunggren, P., Maahs, D. M., Johansson, P., Ludvigsson, J., Pyle, L., Sippl, R., . . . Snell-Bergeon, J. (2016). Reduced brachial artery distensibility in patients with type 1 diabetes. Journal of diabetes and its complications, 30(5), 893-897.
Open this publication in new window or tab >>Reduced brachial artery distensibility in patients with type 1 diabetes
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2016 (English)In: Journal of diabetes and its complications, ISSN 1056-8727, E-ISSN 1873-460X, Vol. 30, no 5, 893-897 p.Article in journal (Refereed) Published
Abstract [en]

Background and aims: In patients with type 1 diabetes mellitus (T1D), cardiovascular disease (CVD) events are more common and occur earlier in life than in non-diabetics. Reduced brachial artery distensibility (BrachD) is an independent risk factor for development of CVD. Our aim was to determine if adults with T1D have lower BrachD compared to adults without diabetes and also to determine how age and gender affect the relationship of BrachD with T1D status. Materials and methods: BrachD was measured using the Dynapulse instrument in 829 participants (352 with T1D, 477 non-diabetics). An ANCOVA model was used to test the association of BrachD with age, sex, and T1D, and the significance of an age*sex*T1D interaction. Results: Mean BrachD was lower in T1D patients vs. controls (6.43 +/- 1.46 vs. 7.16 +/- 1.48 % change per mmHg, p amp;lt; 0.0001). In a model adjusted for age, T1D, and sex, the interaction of age*T1D*sex was significant (p = 0.0045). Younger women both with and without T1D had higher BrachD than men with and without T1D, but older women with and without T1D had lower BrachD compared to older men with and without T1D. Women with T1D had a steeper decline in BrachD with age than nondiabetic women. Conclusions: BrachD is lower in T1D patients than in non-diabetics, indicating increased vascular stiffness. Younger females have higher BrachD than males, but the decline with age in BrachD is steeper for women, particularly among those with T1D. BrachD may be an inexpensive, non-invasive method to ascertain increased CVD risk in this population. (C) 2016 Elsevier Inc. All rights reserved.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE INC, 2016
Keyword
Brachial artery distensibility; Arterial stiffness; Type 1 diabetes; Coronary artery calcium; Cardiovascular disease
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:liu:diva-130402 (URN)10.1016/j.jdiacomp.2016.03.004 (DOI)000378759700024 ()27056753 (PubMedID)
Note

Funding Agencies|NIH [M01 RR000051]; NIH National Heart, Lung and Blood Institute [R01 HL61753, R01 HL079611, HL113029]; JDRF grant [17-2013-313]; American Diabetes Association [1-10-JF-50, 7-13-CD-10]; Diabetes Endocrinology Research Center Clinical Investigation Core [P30 DK57516]; CTSI [UL1 TR000154]

Available from: 2016-08-15 Created: 2016-08-05 Last updated: 2017-11-28
Ludvigsson, J. (2016). Therapies to Preserve beta-Cell Function in Type 1 Diabetes. Drugs, 76(2), 169-185.
Open this publication in new window or tab >>Therapies to Preserve beta-Cell Function in Type 1 Diabetes
2016 (English)In: Drugs, ISSN 0012-6667, E-ISSN 1179-1950, Vol. 76, no 2, 169-185 p.Article, review/survey (Refereed) Published
Abstract [en]

In spite of modern techniques, the burden for patients with type 1 diabetes mellitus will not disappear, and type 1 diabetes will remain a life-threatening disease causing severe complications and increased mortality. We have to learn of ways to stop the destructive process, preserve residual insulin secretion or even improve the disease via beta-cell regeneration. This will give a milder disease, a more stable metabolism, simpler treatment and perhaps even cure. Therapies based on single drugs have not shown sufficient efficacy; however, there are several treatments with encouraging efficacy and no apparent, or rather mild, adverse events. As the disease process is heterogeneous, treatments have to be chosen to fit relevant subgroups of patients, and step by step efficacy can possibly be improved by the use of combination therapies. Thus immunosuppressive therapies like anti-CD3 and anti-CD20 monoclonal antibodies might be combined with fusion proteins such as etanercept [tumor necrosis factor (TNF)-alpha inhibitor] and/or abatacept (CTLA4-Ig) early after onset to stop the destructive process, supported by beta-cell protective agents. The effect may be prolonged by using autoantigen therapy [glutamate decarboxylase (GAD) proinsulin], and by adding agents facilitating beta-cell regeneration [e.g. glucagon-like peptide-1 (GLP-1)] there should be a good chance to make the disease milder, perhaps leading to cure in some patients.

Place, publisher, year, edition, pages
ADIS INT LTD, 2016
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-124627 (URN)10.1007/s40265-015-0511-x (DOI)000368159400002 ()26645223 (PubMedID)
Note

Funding Agencies|Diamyd Medical

Available from: 2016-02-09 Created: 2016-02-08 Last updated: 2017-06-09
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