| 1. |
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| 2. |
- Charalampopoulos, Dimitrios, et al.
(author)
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Exploring Variation in Glycemic Control Across and Within Eight High-Income Countries: A Cross-sectional Analysis of 64,666 Children and Adolescents With Type 1 Diabetes
- 2018
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In: Diabetes Care. - : AMER DIABETES ASSOC. - 0149-5992 .- 1935-5548. ; 41:6, s. 1180-1187
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Journal article (peer-reviewed)abstract
- OBJECTIVE International studies on childhood type 1 diabetes (T1D) have focused on whole-country mean HbA(1c) levels, thereby concealing potential variations within countries. We aimed to explore the variations in HbA(1c) across and within eight high-income countries to best inform international benchmarking and policy recommendations. RESEARCH DESIGN AND METHODS Data were collected between 2013 and 2014 from 64,666 children with T1D who were amp;lt; 18 years of age across 528 centers in Germany, Austria, England, Wales, U.S., Sweden, Denmark, and Norway. We used fixed-and random-effects models adjusted for age, sex, diabetes duration, and minority status to describe differences between center means and to calculate the proportion of total variation in HbA(1c) levels that is attributable to between-center differences (intraclass correlation [ICC]). We also explored the association between within-center variation and childrens glycemic control. RESULTS Sweden had the lowest mean HbA(1c) (59mmol/mol [7.6%]) and together with Norway and Denmark showed the lowest between-center variations (ICC amp;lt;= 4%). Germany and Austria had the next lowest mean HbA(1c) (61-62 mmol/mol [7.7-7.8%]) but showed the largest center variations (ICC similar to 15%). Centers in England, Wales, and the U.S. showed low-to-moderate variation around high mean values. In pooled analysis, differences between counties remained significant after adjustment for children characteristics and center effects (P value amp;lt; 0.001). Across all countries, children attending centers with more variable glycemic results had higher HbA(1c) levels (5.6mmol/mol [0.5%] per 5mmol/mol [0.5%] increase in center SD of HbA(1c) values of all children attending a specific center). CONCLUSIONS A tsimilar average levels of HbA(1c), countries display different levels of center variation. The distribution of glycemic achievement within countries should be considered in developing informed policies that drive quality improvement.
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| 3. |
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| 4. |
- Andersen, Marie Louise M., et al.
(author)
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Association between autoantibodies to the Arginine variant of the Zinc transporter 8 (ZnT8) and stimulated C-peptide levels in Danish children and adolescents with newly diagnosed type 1 diabetes
- 2012
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In: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 13:6, s. 454-462
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Journal article (peer-reviewed)abstract
- Background The zinc transporter 8 (ZnT8) was recently identified as a common autoantigen in type 1 diabetes (T1D) and inclusion of ZnT8 autoantibodies (ZnT8Ab) was found to increase the diagnostic specificity of T1D. Objectives The main aims were to determine whether ZnT8Ab vary during follow-up 1 year after diagnosis, and to relate the reactivity of three types of ZnT8Ab to the residual stimulated C-peptide levels during the first year after diagnosis. Subjects A total of 129 newly diagnosed T1D patients <15 years was followed prospectively 1, 3, 6, and 12 months after diagnosis. Methods Hemoglobin A1c, meal-stimulated C-peptide, ZnT8Ab, and other pancreatic autoantibodies were measured at each visit. Patients were genotyped for the rs13266634 variant at the SLC30A8 gene and HLA-DQ alleles. Results The levels of all ZnT8Ab [ZnT8Arg (arginine), ZnT8Trp (tryptophan), ZnT8Gln (glutamine)] tended to decrease during disease progression. A twofold higher level of ZnT8Arg and ZnT8Gln was associated with 4.6%/5.2% (p = 0.02), 5.3%/8.2% (p = 0.02) and 8.9%/9.7% (p = 0.004) higher concentrations of stimulated C-peptide 3, 6, and 12 months after diagnosis. The TT genotype carriers of the SLC30A8 gene had 45.8% (p = 0.01) and 60.1% (p = 0.002) lower stimulated C-peptide 6 and 12 months after diagnosis compared to the CC and the CT genotype carriers in a recessive model. Conclusions The levels of the Arg variant of the ZnT8 autoantibodies are associated with higher levels of stimulated C-peptide after diagnosis of T1D and during follow-up. Carriers of the TT genotype of the SLC30A8 gene predict lower stimulated C-peptide levels 12 months after diagnosis.
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| 5. |
- Birkebaek, Niels H., et al.
(author)
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Impact of the COVID-19 pandemic on long-term trends in the prevalence of diabetic ketoacidosis at diagnosis of paediatric type 1 diabetes: an international multicentre study based on data from 13 national diabetes registries
- 2022
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In: The Lancet Diabetes and Endocrinology. - : ELSEVIER SCIENCE INC. - 2213-8587 .- 2213-8595. ; 10:11, s. 786-794
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Journal article (peer-reviewed)abstract
- Background An increased prevalence of diabetic ketoacidosis at diagnosis of type 1 diabetes in children was observed in various diabetes centres worldwide during the COVID-19 pandemic. We aimed to evaluate trends in the prevalence of diabetic ketoacidosis at diagnosis of paediatric type 1 diabetes before and during the COVID-19 pandemic, and to identify potential predictors of changes in diabetic ketoacidosis prevalence during the pandemic.Methods For this international multicentre study, we used data from 13 national diabetes registries (Australia, Austria, Czechia, Denmark, Germany, Italy, Luxembourg, New Zealand, Norway, Slovenia, Sweden, USA [Colorado], and Wales). The study population comprised 104 290 children and adolescents aged 6 months to younger than 18 years, who were diagnosed with type 1 diabetes between Jan 1, 2006, and Dec 31, 2021. The observed diabetic ketoacidosis prevalence in 2020 and 2021 was compared to predictions based on trends over the pre-pandemic years 2006-19. Associations between changes in diabetic ketoacidosis prevalence and the severity of the COVID-19 pandemic and containment measures were examined with excess all-cause mortality in the whole population and the Stringency Index from the Oxford COVID-19 Government Response Tracker.Findings 87 228 children and adolescents were diagnosed with type 1 diabetes between 2006 and 2019, 8209 were diagnosed in 2020, and 8853 were diagnosed in 2021. From 2006 to 2019, diabetic ketoacidosis at diagnosis of type 1 diabetes was present in 23 775 (27middot3%) of 87 228 individuals and the mean annual increase in the prevalence of diabetic ketoacidosis in the total cohort from 2006 to 2019 was 1middot6% (95% CI 1middot3 to 1middot9). The adjusted observed prevalence of diabetic ketoacidosis at diagnosis of type 1 diabetes was 39middot4% (95% CI 34middot0 to 45middot6) in 2020 and 38middot9% (33middot6 to 45middot0) in 2021, significantly higher than the predicted prevalence of 32middot5% (27middot8 to 37middot9) for 2020 and 33middot0% (28middot3 to 38middot5) for 2021 (p<0middot0001 for both years). The prevalence of diabetic ketoacidosis was associated with the pandemic containment measures, with an estimated risk ratio of 1middot037 (95% CI 1middot024 to 1middot051; p<0middot0001) per ten-unit increase in the Stringency Index for 2020 and 1middot028 (1middot009 to 1middot047; p=0middot0033) for 2021, but was not significantly associated with excess all-cause mortality.Interpretation During the COVID-19 pandemic, there was a marked exacerbation of the pre-existing increase in diabetic ketoacidosis prevalence at diagnosis of type 1 diabetes in children. This finding highlights the need for early and timely diagnosis of type 1 diabetes in children and adolescents.Funding German Federal Ministry for Education and Research, German Robert Koch Institute, German Diabetes Association, German Diabetes Foundation, Slovenian Research Agency, Welsh Government, Central Denmark Region, and Swedish Association of Local Authorities and Regions.Copyright (c) 2022 Elsevier Ltd. All rights reserved.
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| 6. |
- Brorsson, Caroline, et al.
(author)
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Correlations between islet autoantibody specificity and the SLC30A8 genotype with HLA-DQB1 and metabolic control in new onset type 1 diabetes
- 2011
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In: Autoimmunity. - : Taylor & Francis. - 0891-6934 .- 1607-842X. ; 44:2, s. 107-114
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Journal article (peer-reviewed)abstract
- We hypothesised that the correlation between autoantibody specificity for the ZnT8 Arg325Trp isoforms and the type 2 diabetes-associated rs13266634 may affect beta-cell function at type 1 diabetes (T ID) onset. To study this, we tested 482 newly diagnosed diabetic probands and 478 healthy siblings from the Danish population-based T1D registry for autoantibodies to ZnT8 (ZnT8A) in addition to GAD65 and IA-2. The prevalence and titres of autoantibodies were correlated with genotypes for rs13266634 and HLA-DQB1, age at diagnosis (AAD) and insulin dose-adjusted HbA1c (IDAA1c), as a proxy for residual beta-cell function. We replicated the correlation between rs13266634 genotypes and specificity for the ZnT8-Argenine (ZnT8R) and ZnT8-Tryptophan (ZnT8W) isoforms previously reported. ZnT8A overlapped substantially with autoantibodies to glutamate decarboxylase 65 (GADA) and IA-2 (IA-2A) and correlated significantly with IA-2A prevalence (p < 2e-16). No effect on IDAA1c was demonstrated for ZnT8A or rs13266634. We found a correlation between ZnT8R positivity and HLA-DQB1*0302 genotypes (p = 0.016), which has not been shown previously. Furthermore, significantly lower ZnT8R and GADA prevalence and titres was found among probands with AAD < 5 years (prevalence: p = 0.004 and p = 0.0001; titres: p = 0.002 and p = 0.001, respectively). The same trend was observed for IA-2A and ZnT8W; however, the difference was non-significant. Our study confirms ZnT8 as a major target for autoantibodies at disease onset in our Danish T1D cohort of children and adolescents, and we have further characterised the relationship between autoantibody specificity for the ZnT8 Arg325Trp epitopes and rs13266634 in relation to established autoantibodies, AAD, measures of beta-cell function and HLA-DQB1 genotypes in T1D.
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| 7. |
- Brorsson, Caroline, et al.
(author)
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Correlations between islet autoantibody specificity and the SLC30A8 genotype with HLA-DQB1 and metabolic control in new onset type 1 diabetes
- 2011
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In: Autoimmunity. - : Informa UK Limited. - 0891-6934 .- 1607-842X. ; 44:2, s. 107-114
-
Journal article (peer-reviewed)abstract
- We hypothesised that the correlation between autoantibody specificity for the ZnT8 Arg325Trp isoforms and the type 2 diabetes-associated rs13266634 may affect beta-cell function at type 1 diabetes (T ID) onset. To study this, we tested 482 newly diagnosed diabetic probands and 478 healthy siblings from the Danish population-based T1D registry for autoantibodies to ZnT8 (ZnT8A) in addition to GAD65 and IA-2. The prevalence and titres of autoantibodies were correlated with genotypes for rs13266634 and HLA-DQB1, age at diagnosis (AAD) and insulin dose-adjusted HbA1c (IDAA1c), as a proxy for residual beta-cell function. We replicated the correlation between rs13266634 genotypes and specificity for the ZnT8-Argenine (ZnT8R) and ZnT8-Tryptophan (ZnT8W) isoforms previously reported. ZnT8A overlapped substantially with autoantibodies to glutamate decarboxylase 65 (GADA) and IA-2 (IA-2A) and correlated significantly with IA-2A prevalence (p < 2e-16). No effect on IDAA1c was demonstrated for ZnT8A or rs13266634. We found a correlation between ZnT8R positivity and HLA-DQB1*0302 genotypes (p = 0.016), which has not been shown previously. Furthermore, significantly lower ZnT8R and GADA prevalence and titres was found among probands with AAD < 5 years (prevalence: p = 0.004 and p = 0.0001; titres: p = 0.002 and p = 0.001, respectively). The same trend was observed for IA-2A and ZnT8W; however, the difference was non-significant. Our study confirms ZnT8 as a major target for autoantibodies at disease onset in our Danish T1D cohort of children and adolescents, and we have further characterised the relationship between autoantibody specificity for the ZnT8 Arg325Trp epitopes and rs13266634 in relation to established autoantibodies, AAD, measures of beta-cell function and HLA-DQB1 genotypes in T1D.
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| 8. |
- Cardwell, Chris R, et al.
(author)
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Birth order and childhood type 1 diabetes risk: a pooled analysis of 31 observational studies
- 2011
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In: INTERNATIONAL JOURNAL OF EPIDEMIOLOGY. - : OXFORD UNIV PRESS, GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND. - 0300-5771 .- 1464-3685. ; 40:2, s. 363-374
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Journal article (peer-reviewed)abstract
- Background The incidence rates of childhood onset type 1 diabetes are almost universally increasing across the globe but the aetiology of the disease remains largely unknown. We investigated whether birth order is associated with the risk of childhood diabetes by performing a pooled analysis of previous studies. Methods Relevant studies published before January 2010 were identified from MEDLINE, Web of Science and EMBASE. Authors of studies provided individual patient data or conducted pre-specified analyses. Meta-analysis techniques were used to derive combined odds ratios (ORs), before and after adjustment for confounders, and investigate heterogeneity. Results Data were available for 6 cohort and 25 case-control studies, including 11 955 cases of type 1 diabetes. Overall, there was no evidence of an association prior to adjustment for confounders. After adjustment for maternal age at birth and other confounders, a reduction in the risk of diabetes in second- or later born children became apparent [fully adjusted OR = 0.90 95% confidence interval (CI) 0.83-0.98; P = 0.02] but this association varied markedly between studies (I-2 = 67%). An a priori subgroup analysis showed that the association was stronger and more consistent in children andlt; 5 years of age (n = 25 studies, maternal age adjusted OR = 0.84 95% CI 0.75, 0.93; I-2 = 23%). Conclusion Although the association varied between studies, there was some evidence of a lower risk of childhood onset type 1 diabetes with increasing birth order, particularly in children aged andlt; 5 years. This finding could reflect increased exposure to infections in early life in later born children.
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| 9. |
- Cardwell, Chris R, et al.
(author)
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Breast-Feeding and Childhood-Onset Type 1 Diabetes A pooled analysis of individual participant data from 43 observational studies
- 2012
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In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 35:11, s. 2215-2225
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Journal article (peer-reviewed)abstract
- OBJECTIVE-To investigate if there is a reduced risk of type 1 diabetes in children breastfed or exclusively breastfed by performing a pooled analysis with adjustment for recognized confounders. less thanbrgreater than less thanbrgreater thanRESEARCH DESIGN AND METHODS-Relevant studies were identified from literature searches using MEDLINE, Web of Science, and EMBASE. Authors of relevant studies were asked to provide individual participant data or conduct prespecified analyses. Meta-analysis techniques were used to combine odds ratios (ORs) and investigate heterogeneity between studies. less thanbrgreater than less thanbrgreater thanRESULTS-Data were available from 43 studies including 9,874 patients with type 1 diabetes. Overall, there was a reduction in the risk of diabetes after exclusive breast-feeding for andgt;2 weeks (20 studies; OR = 0.75, 95% CI 0.64-0.88), the association after exclusive breast-feeding for andgt;3 months was weaker (30 studies; OR = 0.87, 95% CI 0.75-1.00), and no association was observed after (nonexclusive) breast-feeding for andgt;2 weeks (28 studies; OR = 0.93, 95% CI 0.81-1.07) or andgt;3 months (29 studies; OR = 0.88, 95% CI 0.78-1.00). These associations were all subject to marked heterogeneity (I-2 = 58, 76, 54, and 68%, respectively). In studies with lower risk of bias, the reduced risk after exclusive breast-feeding for andgt;2 weeks remained (12 studies; OR = 0.86, 95% CI 0.75-0.99), and heterogeneity was reduced (I-2 = 0%). Adjustments for potential confounders altered these estimates very little. less thanbrgreater than less thanbrgreater thanCONCLUSIONS-The pooled analysis suggests weak protective associations between exclusive breast-feeding and type 1 diabetes risk. However, these findings are difficult to interpret because of the marked variation in effect and possible biases (particularly recall bias) inherent in the included studies.
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| 10. |
- Cardwell, Chris R, et al.
(author)
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Interbirth Interval Is Associated With Childhood Type 1 Diabetes Risk
- 2012
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In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 61:3, s. 702-707
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Journal article (peer-reviewed)abstract
- Short interbirth interval has been associated with maternal complications and childhood autism and leukemia, possibly due to deficiencies in maternal micronutrients at conception or increased exposure to sibling infections. A possible association between interbirth interval and subsequent risk of childhood type 1 diabetes has not been investigated. A secondary analysis of 14 published observational studies of perinatal risk factors for type 1 diabetes was conducted. Risk estimates of diabetes by category of interbirth interval were calculated for each study. Random effects models were used to calculate pooled odds ratios (ORs) and investigate heterogeneity between studies. Overall, 2,787 children with type 1 diabetes were included. There was a reduction in the risk of childhood type 1 diabetes in children born to mothers after interbirth intervals andlt;3 years compared with longer interbirth intervals (OR 0.82 [95% CI 0.72-0.93]). Adjustments for various potential confounders little altered this estimate. In conclusion, there was evidence of a 20% reduction in the risk of childhood diabetes in children born to mothers after interbirth intervals andlt;3 years.
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| 11. |
- Cardwell, Chris R, et al.
(author)
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Maternal Age at Birth and Childhood Type 1 Diabetes: A Pooled Analysis of 30 Observational Studies
- 2010
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In: DIABETES. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 59:2, s. 486-494
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Journal article (peer-reviewed)abstract
- OBJECTIVE-The aim if the study was to investigate whether children born to older mothers have an increased risk of type 1 diabetes by performing a pooled analysis of previous studies using individual patient data to adjust for recognized confounders. RESEARCH DESIGN AND METHODS-Relevant studies published before June 2009 were identified from MEDLINE, Web of Science, and EMBASE. Authors of studies were contacted and asked to provide individual patient data or conduct prespecified analyses. Risk estimates of type 1 diabetes by maternal age were calculated for each study, before and after adjustment for potential confounders. Meta-analysis techniques were used to derive combined odds ratios and to investigate heterogeneity among studies. RESULTS-Data were available for 5 cohort and 25 case-control studies, including 14,724 cases of type 1 diabetes. Overall, there was, on average, a 5% (95% CI 2-9) increase in childhood type 1 diabetes odds per 5-year increase in maternal age (P = 0.006), but there was heterogeneity among studies (heterogeneity I-2 = 70%). In studies with a low risk of bias, there was a more marked increase in diabetes odds of 10% per 5-year increase in maternal age. Adjustments for potential confounders little altered these estimates. CONCLUSIONS-There was evidence of a weak but significant linear increase in the risk of childhood type 1 diabetes across the range of maternal ages, but the magnitude of association varied between studies. A very small percentage of the increase in the incidence of childhood type 1 diabetes in recent years could be explained by increases in maternal age.
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| 12. |
- Eising, Stefanie, et al.
(author)
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Type 1 diabetes risk analysis on dried blood spot samples from population-based newborns: design and feasibility of an unselected case-control study
- 2007
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In: Paediatric and Perinatal Epidemiology. - : Wiley. - 0269-5022 .- 1365-3016. ; 21:6, s. 507-517
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Journal article (peer-reviewed)abstract
- Development of type 1 diabetes mellitus (T1D) may be triggered pre- or perinatally by multiple factors. Identifying new predisposing T1D markers or combinations of markers in a large, well-characterised case-control collection may be important for future T1D prevention. The present work describes the design and feasibility of a large and unselected case-control study, which will define and evaluate prediction criteria for T1D at the time of birth. Danish registries (Biological Specimen Bank for Neonatal Screening, and the National Discharge Registry) made it possible to identify and collect dried blood spots (DBS) from newborns who later developed T1D (cases) born 1981-2002. DBS samples from 2086 cases and two matching control subjects per case were analysed for genetic and immune factors that are associated with T1D: (a) candidate genes (HLA, INS and CTLA4), (b) cytokines and inflammatory markers, (c) islet auto-antibodies (GAD65A, IA-2A). The objective of the study was to define reliable prediction tools for T1D using samples available at the time of birth. In a unique approach, the study linked a large unselected and population-based sample resource to well-ascertained clinical databases and advanced technology. It combined genetic, immunological and demographic data to develop prediction algorithms. It also provided a resource for future studies in which new genetic markers can be included as they are identified.
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| 13. |
- Fredheim, Siri, et al.
(author)
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Equal access to health care may diminish the differences in outcome between native and immigrant patients with type 1 diabetes
- 2014
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In: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 15:7, s. 519-527
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Journal article (peer-reviewed)abstract
- Background/Objective: Previous studies have found that ethnicity influences glycemic control. We hypothesized that differences between Nordic and non-Nordic patients are less pronounced for children with type 1 diabetes in high incidence countries in Northern Europe. Research design and methods: We investigated patients aged 0-15 yr in national pediatric registers in Denmark (D), Iceland (I), Norway (N), and Sweden (S) (2006-2009). Ethnic origin was defined by maternal country of birth as being Nordic or non-Nordic (other countries). Results: The cohort (n= 11,908, 53.0% boys, onset age 7.7 (3.9) yr, diabetes duration 6.1 (3.6) yr, [mean, (SD)]) comprised 921 (7.7%) non-Nordic patients. The frequencies of non-Nordic patients according to country of residence were: 5.7% (D), 2.7% (I), 5.5% (N), and 9.4% (S). Sex distribution and BMI z-score did not differ between Nordic and non-Nordic patients, but non-Nordic patients were 0.5 yr younger at onset than Nordic patients (p< 0.0006). Non-Nordic patients had a lower number of daily insulin bolus injections and higher daily insulin doses compared to their Nordic peers. Patients of non-Nordic origin had slightly higher HbA1c levels (0.6-2.9 mmol/mol, p< 0.001) and, with the exception of Norway, were less frequently treated with CSII (p= 0.002) after adjusting for confounders. Conclusions: The reported differences in glycemic regulation between Nordic and non-Nordic type 1 diabetes children and adolescents in four Nordic countries are diminutive, but persist after accounting for treatment intensity.
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| 14. |
- Kyhl, Frederik, et al.
(author)
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The risk of Type 1 diabetes in children born after ART: a Nordic cohort study from the CoNARTaS group
- 2024
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In: HUMAN REPRODUCTION OPEN. - 2399-3529. ; 2024:2
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Journal article (peer-reviewed)abstract
- STUDY QUESTION Do children born after ART have a higher risk of developing Type 1 diabetes (DM1) than children conceived without ART?SUMMARY ANSWER The risk of DM1 was similar for children conceived with and without ART, and there were no clear differences in risk according to method of fertility treatment.WHAT IS KNOWN ALREADY ART is associated with a higher risk of adverse perinatal outcomes, and the risk depends on the method of ART. The Developmental Origins of Health and Disease theory proposes that prenatal stress can provoke changes in endocrine processes which impact health later in life.STUDY DESIGN, SIZE, DURATION A Nordic register-based cohort study was carried out, including all children born in Denmark (birth years 1994-2014), Finland (1990-2014), and Norway (1984-2015). The study included 76 184 liveborn singletons born after ART and 4 403 419 born without ART. Median follow-up was 8.3 and 13.7 years in the ART and non-ART group, respectively.PARTICIPANTS/MATERIALS, SETTING, METHODS The cohort, initiated by the Committee of Nordic Assisted Reproductive Technology and Safety (CoNARTaS), was established by linking national registry data from the medical birth registries and national patient registries available in the Nordic countries. We performed multivariable logistic regression analyses for the birth year intervals 1984-1990, 1991-1995, 1996-2000, 2001-2005, 2006-2010, and 2011-2015, while adjusting for year of birth within each interval, sex of the child, parity, maternal age, maternal diabetes, and maternal smoking during pregnancy as potential confounders.MAIN RESULTS AND THE ROLE OF CHANCE During follow-up, 259 (3.4 parts per thousand) children born after ART were diagnosed with DM1, while this was the case for 22 209 (5.0 parts per thousand) born without ART, corresponding to an adjusted odds ratio of 0.98 (95% CI: 0.861.11). Within the different birth year intervals, no significant difference in risk of DM1 between the two groups was found, except for the youngest cohort of children born 2011-2015 where ART was associated with a higher risk of DM1. We found no significant differences in risk of DM1 when comparing children born after IVF versus ICSI or fresh versus frozen embryo transfer, but with only few cases in each group.LIMITATIONS, REASONS FOR CAUTION The main limitation of the study is the relatively short follow-up time. The incidence rate of DM1 peaks during ages 10-14 years, hence a longer follow-up would benefit all analyses and, in particular, the subgroup analyses.WIDER IMPLICATIONS OF THE FINDINGS Overall, our findings are reassuring especially considering the concomitantly increasing number of children born from ART and the increasing incidence of DM1 globally.STUDY FUNDING/COMPETING INTEREST(S) This Nordic registry study has been supported by the Nordic Trial Alliance/NORDFORSK and Rigshospitalets Research Foundation. The funding sources had no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. None of the authors has any conflicts of interest to declare regarding this study.TRIAL REGISTRATION NUMBER ISRCTN11780826.
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| 15. |
- Maffeis, Claudio, et al.
(author)
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Prevalence of underweight, overweight, and obesity in children and adolescents with type 1 diabetes: Data from the international SWEET registry.
- 2018
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In: Pediatric diabetes. - : Hindawi Limited. - 1399-5448 .- 1399-543X. ; 19:7, s. 1211-1220
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Journal article (peer-reviewed)abstract
- To assess the prevalence of underweight (UW), overweight (OW), and obesity in children and adolescents with type 1 diabetes (T1D).An international cross-sectional study including 23026 T1D children (2-18 years, duration of diabetes ≥1year) participating in the SWEET prospective, multicenter diabetes registry. Body mass index SD score (BMI-SDS) was calculated using the World Health Organization BMI charts. Children were categorized as UW (BMI-SDS<-2SD), OW (+1SD+2SD). Hierarchic regression models were applied with adjustment for sex, age, and duration of diabetes.The prevalence of UW, OW, and obesity was: 1.4%, 22.3%, and 7.3% in males and 0.6%, 27.2%, and 6.8% in females. Adjusted BMI-SDS was significantly higher in females than in males (mean±SEM: 0.54±0.05 vs 0.40±0.05, P<0.0001). In males, BMI-SDS significantly decreased by age (P<0.0001) in the first three age categories 0.61±0.06 (2 to <10years), 0.47±0.06 (10 to <13 years), 0.34±0.05 (13 to <16 years). In females, BMI-SDS showed a U-shaped distribution by age (P<0.0001): 0.54±0.04 (2 to <10years), 0.39±0.04 (10 to <13 years), 0.55±0.04 (13 to <16 years). BMI-SDS increased by diabetes duration (<2years: 0.38±0.05, 2 to <5years: 0.44±0.05, and ≥5years: 0.50±0.05, P<0.0001). Treatment modality did not affect BMI-SDS. Adjusted HbA1c was significantly higher in females than in males (8.20%±0.10% vs 8.06%±0.10%, P<0.0001). In both genders, the association between HbA1c and BMI-SDS was U-shaped with the highest HbA1c in the UW and obesity groups.The high rate of OW and obesity (31.8%) emphasize the need for developing further strategies to prevent and treat excess fat accumulation in T1D.
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| 16. |
- Nielsen, Lotte B., et al.
(author)
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Relationship between ZnT8Ab, the SLC30A8 gene and disease progression in children with newly diagnosed type 1 diabetes
- 2011
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In: Autoimmunity. - : Informa UK Limited. - 0891-6934 .- 1607-842X. ; 44:8, s. 616-623
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Journal article (peer-reviewed)abstract
- Autoantibodies against the newly established autoantigen in type 1 diabetes, zinc transporter 8, ZnT8, are presented as two types, ZnT8RAb and ZnT8WAb. The rs13266634 variant of the SLC30A8 gene has recently been found to determine the type of ZnT8Ab. The aim of this study was to explore the impact of this genetic variant and the ZnT8Ab on the residual beta-cell function during disease progression the first year after disease diagnosis in children with newly diagnosed type 1 diabetes. This cohort consists of 257 children aged < 16 years, all patients were newly diagnosed with type 1 diabetes. A Boost-test was carried out at 1, 6, and 12 months to characterize the residual beta-cell function. Carriers of the CC and CT genotype groups of the rs13266634 SNP of the SLC30A8 gene had higher stimulated C-peptide levels the first year after onset compared with those of the TT genotype group (29%, p = 0.034). CC genotype carriers were highly associated with the presence of ZnT8RAb subtype during disease progression (compared with TT, p < 0.0001). On the other hand, the TT genotype was associated with the presence of ZnT8WAb subtype during disease progression (compared with CC, p < 0.0001). The C allele of the SLC30A8 gene is associated with preserved beta-cell function in type 1 diabetes patients. The genetic determination of the rs13266634 variant on the ZnT8Ab specificity is sustained the first 12 months after the diagnosis of type 1 diabetes in a pediatric cohort.
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| 17. |
- Patterson, Christopher C., et al.
(author)
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Trends and cyclical variation in the incidence of childhood type 1 diabetes in 26 European centres in the 25year period 1989-2013 : a multicentre prospective registration study
- 2019
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In: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 62:3, s. 408-417
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Journal article (peer-reviewed)abstract
- Aims/hypothesis: Against a background of a near-universally increasing incidence of childhood type 1 diabetes, recent reports from some countries suggest a slowing in this increase. Occasional reports also describe cyclical variations in incidence, with periodicities of between 4 and 6years.Methods: Age/sex-standardised incidence rates for the 0- to 14-year-old age group are reported for 26 European centres (representing 22 countries) that have registered newly diagnosed individuals in geographically defined regions for up to 25years during the period 1989-2013. Poisson regression was used to estimate rates of increase and test for cyclical patterns. Joinpoint regression software was used to fit segmented log-linear relationships to incidence trends.Results: Significant increases in incidence were noted in all but two small centres, with a maximum rate of increase of 6.6% per annum in a Polish centre. Several centres in high-incidence countries showed reducing rates of increase in more recent years. Despite this, a pooled analysis across all centres revealed a 3.4% (95% CI 2.8%, 3.9%) per annum increase in incidence rate, although there was some suggestion of a reduced rate of increase in the 2004-2008 period. Rates of increase were similar in boys and girls in the 0- to 4-year-old age group (3.7% and 3.7% per annum, respectively) and in the 5- to 9-year-old age group (3.4% and 3.7% per annum, respectively), but were higher in boys than girls in the 10- to 14-year-old age group (3.3% and 2.6% per annum, respectively). Significant 4year periodicity was detected in four centres, with three centres showing that the most recent peak in fitted rates occurred in 2012.Conclusions/interpretation: Despite reductions in the rate of increase in some high-risk countries, the pooled estimate across centres continues to show a 3.4% increase per annum in incidence rate, suggesting a doubling in incidence rate within approximately 20years in Europe. Although four centres showed support for a cyclical pattern of incidence with a 4year periodicity, no plausible explanation for this can be given.
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| 18. |
- Samuelsson, Ulf, et al.
(author)
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Geographical variation in the incidence of type 1 diabetes in the Nordic countries : A study within NordicDiabKids
- 2020
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In: Pediatric Diabetes. - : Blackwell Publishing. - 1399-543X .- 1399-5448. ; 21:2, s. 259-265
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Journal article (peer-reviewed)abstract
- Background: The incidence of type 1 diabetes (T1D) is high in the Nordic countries with geographic differences between as well as within countries. Objective: To describe the geographical distribution of the incidence of T1D among children in four Nordic countries, an area where the population is considered genetically similar.Methods: Data on children 0 to 14 years of age and diagnosed with T1D 2006 to 2011 was collected from four Nordic national pediatric quality diabetes registries. Data included year of diagnosis (2006-2011), sex, and age at diagnosis. Figures for number of children at risk during 2006 to 2011—as well as total population, proportion with foreign background and size of populated areas of geographic regions—were collected from official statistics.Results: The total incidence during the study period for all four countries was 35.7/100 000 person years but differed between the countries (range 18.2-44.1; P <.001). The incidence difference between the countries was most obvious in the highest age group, 10 to 14 years of age, whereas there was no difference in the youngest age group 0 to 5 years of age. Iceland had similar incidence in the entire country, whereas the other countries had areas with different incidence. Densely populated areas, such as major cities, had the lowest incidence.Conclusion: The incidence of T1D differed between the Nordic countries and also between the neighboring countries and generally decreased with population density. This indicates that environmental factors may contribute to the level of incidence of T1D.
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| 19. |
- Svensson, Jannet, et al.
(author)
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Few differences in cytokines between patients newly diagnosed with type 1 diabetes and their healthy siblings
- 2012
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In: Human Immunology. - : Elsevier BV. - 0198-8859. ; 73:11, s. 1116-1126
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Journal article (peer-reviewed)abstract
- The cause of the worldwide increase in type 1 diabetes (T1D) is largely unknown. T cells are thought to play a role in disease progression. In contemporary research over the last decade, age- and gender-specific serum levels as well as changes of Th1 and Th2-related cytokines are not well described. From a population-based register of children diagnosed from 1997 to 2005 this study explores eight different cytokines at time of diagnosis. Only TGF-beta and IL-18 showed higher levels in patients compared to siblings in an adjusted model (p < 0.01): whereas the other seven cytokines were not significantly different. IL-1 beta, IL-18, IL-12, IL-10 and IL-4 were significantly higher among the youngest children and males had significantly lower levels of IL-10 and IL-12 but higher levels of TNF-alpha. During the nine-year study all of the cytokines increased except TGF-beta, which showed a slight decrease over time. The cytokine levels tended to be highest during summer and were most pronounced for IL-1 beta and TNF-alpha. In conclusion, serum levels of known beta-cell cytotoxic cytokines were indifferent in patients and siblings, while gender, age and season appear to exert some influence on the serum level and need to be explored further. The influence of time on systemic levels cannot be ignored and may reflect decay or environmental impact on the immune system. (C) 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.
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| 20. |
- Svensson, Jannet, et al.
(author)
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High levels of immunoglobulin E and a continuous increase in immunoglobulin G and immunoglobulin M by age in children with newly diagnosed type 1 diabetes
- 2012
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In: Human Immunology. - : Elsevier BV. - 0198-8859. ; 73:1, s. 17-25
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Journal article (peer-reviewed)abstract
- The incidence of type 1 diabetes (T1D) is increasing, either because of environmental factors accelerating onset of the disease or because of inducement of autoimmune diabetes in children who previously were at lower risk. High levels of immunoglobulin (Ig), specifically, IgM and IgA, and a low level of IgG were reported in adult patients; however no studies have analyzed the increasing incidence in relation to Ig levels. Our aim was to describe Ig in children newly diagnosed with diabetes and in their healthy siblings. Children with T1D expressed significantly lower IgG (p < 0.01) and higher IgA levels (p = 0.045), whereas no differences in IgE or IgM (p > 0.5) levels were found. Age-specific levels were unchanged over a 9-year period. In patients and siblings IgG. IgA and IgE increased by age (p < 0.001); which was in contrast to IgM (p > 0.05). The continued increase in IgG levels by age indicates that adult levels are reached later than in previously studied cohorts, thereby indicating a slower maturation of the immune system. (C) 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.
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| 21. |
- Szypowska, Agnieszka, et al.
(author)
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Insulin pump therapy in children with type 1 diabetes: analysis of data from the SWEET registry.
- 2016
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In: Pediatric diabetes. - : Hindawi Limited. - 1399-5448 .- 1399-543X. ; 17 Suppl 23, s. 38-45
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Journal article (peer-reviewed)abstract
- Intensified insulin delivery using multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII) is recommended in children with type 1 diabetes (T1D) to achieve good metabolic control.To examine the frequency of pump usage in T1D children treated in SWEET (Better control in Paediatric and Adolescent diabeteS: Working to crEate CEnTers of Reference) centers and to compare metabolic control between patients treated with CSII vs MDI.This study included 16 570 T1D children participating in the SWEET prospective, multicenter, standardized diabetes patient registry. Datasets were aggregated over the most recent year of treatment for each patient. Data were collected until March 2016. To assess the organization of pump therapy a survey was carried out.Overall, 44.4% of T1D children were treated with CSII. The proportion of patients with pump usage varied between centers and decreased with increasing age compared with children treated with MDI. In a logistic regression analysis adjusting for age, gender and diabetes duration, the use of pump was associated with both: center size [odd ratio 1.51 (1.47-1.55), P < .0001) and the diabetes-related expenditure per capita [odd ratio 1.55 (1.49-1.61), P < .0001]. Linear regression analysis, adjusted for age, gender, and diabetes duration showed that both HbA1c and daily insulin dose (U/kg/d) remained decreased in children treated with CSII compared to MDI (P < .0001).Insulin pump therapy is offered by most Sweet centers. The differences between centers affect the frequency of use of modern technology. Despite the heterogeneity of centers, T1D children achieve relatively good metabolic control, especially those treated with insulin pumps and those of younger age.
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| 22. |
- Söderström, Ulf, 1947-
(author)
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Type 1 diabetes in children with non-Swedish background : epidemiology and clinical outcome
- 2014
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Doctoral thesis (other academic/artistic)abstract
- Sweden holds third place of diabetes incidence in young people after Finland and Sardinia. One fifth of the population is nowadays of foreign descent. We have a substantial number of immigrants from countries where the risk for T1D is considerably lower. Migration as a natural experiment is a concept to assess the risk for diabetes in offspring of immigrant parents and assess the interaction between genetics (genotype) and the impact of environment (phenotype).Aims: To study the risk of incurring diabetes for children of immigrant parents living in Sweden (I) and further study the risk if the child is born in Sweden or not (II); to specifically study and evaluate if children from East Africa have increased risk to develop T1D (III). To investigate if clinical and sociodemographic status at T1D onset differs between immigrant children compared to their Swedish indigenous peers (IV). Finally to study the clinical outcome and the impact of socio-demographic factors at diabetes onset after three years of treatment (V).Methods: All five studies are observational, nationwide and population based, on prospectively collected data. Statistics mainly by logistic and linear regressions.Results: Parental country of origin is a strong determinant for diabetes in the offspring. Children born to immigrant parents seem to keep their low risk compared to their Swedish peers (I). When adding the factor of being born in Sweden, the pattern changed; there was a significantly (p < 0.001) increased risk for T1D if the child was born in Sweden (II). East Africans have a substantial risk for T1D and especially if the children are born in Sweden (III). Immigrant children and adolescents have worse metabolic start at T1D onset compared to their indigenous Swedish peers (IV). After 3 years of treatment, the immigrant children had a sustained higher median HbA1c, compared to their Swedish peers (V).Conclusions: Genotype and influences during fetal life or early infancy have an important impact for the risk of T1D pointing towards epigenetics playing a substantial role. Children with an origin in East Africa have a high risk of incurring T1D. Immigrant children have worse metabolic start at T1D onset, which sustains after three years of treatment
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| 23. |
- Thorsen, Steffen U, et al.
(author)
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Interaction Between Dietary Iron Intake and Genetically Determined Iron Overload : Risk of Islet Autoimmunity and Progression to Type 1 Diabetes in the TEDDY Study
- 2023
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In: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 46:5, s. 1014-1018
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To examine whether iron intake and genetically determined iron overload interact in predisposing to the development of childhood islet autoimmunity (IA) and type 1 diabetes (T1D).RESEARCH DESIGN AND METHODS: In The Environmental Determinants of Diabetes in the Young (TEDDY) study, 7,770 genetically high-risk children were followed from birth until the development of IA and progression to T1D. Exposures included energy-adjusted iron intake in the first 3 years of life and a genetic risk score (GRS) for increased circulating iron.RESULTS: We found a U-shaped association between iron intake and risk of GAD antibody as the first autoantibody. In children with GRS ≥2 iron risk alleles, high iron intake was associated with an increased risk of IA, with insulin as first autoantibody (adjusted hazard ratio 1.71 [95% CI 1.14; 2.58]) compared with moderate iron intake.CONCLUSIONS: Iron intake may alter the risk of IA in children with high-risk HLA haplogenotypes.
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