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- Anand, Vibha, et al.
(författare)
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Islet Autoimmunity and HLA Markers of Presymptomatic and Clinical Type 1 Diabetes : Joint Analyses of Prospective Cohort Studies in Finland, Germany, Sweden, and the U.S
- 2021
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 44, s. 2269-2276
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To combine prospective cohort studies, by including HLA harmonization, and estimate risk of islet autoimmunity and progression to clinical diabetes.RESEARCH DESIGN AND METHODS: For prospective cohorts in Finland, Germany, Sweden, and the U.S., 24,662 children at increased genetic risk for development of islet autoantibodies and type 1 diabetes have been followed. Following harmonization, the outcomes were analyzed in 16,709 infants-toddlers enrolled by age 2.5 years.RESULTS: In the infant-toddler cohort, 1,413 (8.5%) developed at least one autoantibody confirmed at two or more consecutive visits (seroconversion), 865 (5%) developed multiple autoantibodies, and 655 (4%) progressed to diabetes. The 15-year cumulative incidence of diabetes varied in children with one, two, or three autoantibodies at seroconversion: 45% (95% CI 40-52), 85% (78-90), and 92% (85-97), respectively. Among those with a single autoantibody, status 2 years after seroconversion predicted diabetes risk: 12% (10-25) if reverting to autoantibody negative, 30% (20-40) if retaining a single autoantibody, and 82% (80-95) if developing multiple autoantibodies. HLA-DR-DQ affected the risk of confirmed seroconversion and progression to diabetes in children with stable single-autoantibody status. Their 15-year diabetes incidence for higher- versus lower-risk genotypes was 40% (28-50) vs. 12% (5-38). The rate of progression to diabetes was inversely related to age at development of multiple autoantibodies, ranging from 20% per year to 6% per year in children developing multipositivity in ≤2 years or >7.4 years, respectively.CONCLUSIONS: The number of islet autoantibodies at seroconversion reliably predicts 15-year type 1 diabetes risk. In children retaining a single autoantibody, HLA-DR-DQ genotypes can further refine risk of progression.
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| 2. |
- Frohnert, Brigitte I., et al.
(författare)
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Refining the Definition of Stage 1 Type 1 Diabetes : An Ontology-Driven Analysis of the Heterogeneity of Multiple Islet Autoimmunity
- 2023
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 46:10, s. 1753-1761
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To estimate the risk of progression to stage 3 type 1 diabetes based on varying definitions of multiple islet autoantibody positivity (mIA). RESEARCH DESIGN AND METHODS Type 1 Diabetes Intelligence (T1DI) is a combined prospective data set of children from Finland, Germany, Sweden, and the U.S. who have an increased genetic risk for type 1 diabetes. Analysis included 16,709 infants-toddlers enrolled by age 2.5 years and comparison between groups using Kaplan-Meier survival analysis. RESULTS Of 865 (5%) children with mIA, 537 (62%) progressed to type 1 diabetes. The 15-year cumulative incidence of diabetes varied from the most stringent definition (mIA/ Persistent/2: two or more islet autoantibodies positive at the same visit with two or more antibodies persistent at next visit; 88% [95% CI 85–92%]) to the least stringent (mIA/Any: positivity for two islet autoantibodies without co-occurring positivity or persistence; 18% [5–40%]). Progression in mIA/Persistent/2 was significantly higher than all other groups (P < 0.0001). Intermediate stringency definitions showed intermediate risk and were significantly different than mIA/Any (P < 0.05); however, differences waned over the 2-year follow-up among those who did not subsequently reach higher stringency. Among mIA/Persistent/2 individuals with three autoantibodies, loss of one autoantibody by the 2-year follow-up was associated with accelerated progression. Age was significantly associated with time from seroconversion to mIA/ Persistent/2 status and mIA to stage 3 type 1 diabetes. CONCLUSIONS The 15-year risk of progression to type 1 diabetes risk varies markedly from 18 to 88% based on the stringency of mIA definition. While initial categorization identifies highest-risk individuals, short-term follow-up over 2 years may help stratify evolving risk, especially for those with less stringent definitions of mIA.
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| 3. |
- Ghalwash, Mohamed, et al.
(författare)
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Islet autoantibody screening in at-risk adolescents to predict type 1 diabetes until young adulthood : a prospective cohort study
- 2023
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Ingår i: The Lancet Child and Adolescent Health. - 2352-4642. ; 7:4, s. 261-268
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Tidskriftsartikel (refereegranskat)abstract
- Background: Screening for islet autoantibodies in children and adolescents identifies individuals who will later develop type 1 diabetes, allowing patient and family education to prevent diabetic ketoacidosis at onset and to enable consideration of preventive therapies. We aimed to assess whether islet autoantibody screening is effective for predicting type 1 diabetes in adolescents aged 10−18 years with an increased risk of developing type 1 diabetes. Methods: Data were harmonised from prospective studies from Finland (the Diabetes Prediction and Prevention study), Germany (the BABYDIAB study), and the USA (Diabetes Autoimmunity Study in the Young and the Diabetes Evaluation in Washington study). Autoantibodies against insulin, glutamic acid decarboxylase, and insulinoma-associated protein 2 were measured at each follow-up visit. Children who were lost to follow-up or diagnosed with type 1 diabetes before 10 years of age were excluded. Inverse probability censoring weighting was used to include data from remaining participants. Sensitivity and the positive predictive value of these autoantibodies, tested at one or two ages, to predict type 1 diabetes by the age of 18 years were the main outcomes. Findings: Of 20 303 children with an increased type 1 diabetes risk, 8682 were included for the analysis with inverse probability censoring weighting. 1890 were followed up to 18 years of age or developed type 1 diabetes between the ages of 10 years and 18 years, and their median follow-up was 18·3 years (IQR 14·5–20·3). 442 (23·4%) of 1890 adolescents were positive for at least one islet autoantibody, and 262 (13·9%) developed type 1 diabetes. Time from seroconversion to diabetes diagnosis increased by 0·64 years (95% CI 0·34–0·95) for each 1-year increment of diagnosis age (Pearson's correlation coefficient 0·88, 95% CI 0·50–0·97, p=0·0020). The median interval between the last prediagnostic sample and diagnosis was 0·3 years (IQR 0·1–1·3) in the 227 participants who were autoantibody positive and 6·8 years (1·6–9·9) for the 35 who were autoantibody negative. Single screening at the age of 10 years was 90% (95% CI 86–95) sensitive, with a positive predictive value of 66% (60–72) for clinical diabetes. Screening at two ages (10 years and 14 years) increased sensitivity to 93% (95% CI 89–97) but lowered the positive predictive value to 55% (49–60). Interpretation: Screening of adolescents at risk for type 1 diabetes only once at 10 years of age for islet autoantibodies was highly effective to detect type 1 diabetes by the age of 18 years, which in turn could enable prevention of diabetic ketoacidosis and participation in secondary prevention trials. Funding: JDRF International.
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| 4. |
- Ghalwash, Mohamed, et al.
(författare)
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Two-age islet-autoantibody screening for childhood type 1 diabetes : a prospective cohort study
- 2022
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Ingår i: The Lancet Diabetes and Endocrinology. - 2213-8587. ; 10:8, s. 589-596
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Tidskriftsartikel (refereegranskat)abstract
- Background: Early prediction of childhood type 1 diabetes reduces ketoacidosis at diagnosis and provides opportunities for disease prevention. However, only highly efficient approaches are likely to succeed in public health settings. We sought to identify efficient strategies for initial islet autoantibody screening in children younger than 15 years. Methods: We harmonised data from five prospective cohorts from Finland (DIPP), Germany (BABYDIAB), Sweden (DiPiS), and the USA (DAISY and DEW-IT) into the Type 1 Diabetes Intelligence (T1DI) cohort. 24 662 children at high risk of diabetes enrolled before age 2 years were included and followed up for islet autoantibodies and diabetes until age 15 years, or type 1 diabetes onset, whichever occurred first. Islet autoantibodies measured included those against glutamic acid decarboxylase, insulinoma antigen 2, and insulin. Main outcomes were sensitivity and positive predictive value (PPV) of detected islet autoantibodies, tested at one or two fixed ages, for diagnosis of clinical type 1 diabetes. Findings: Of the 24 662 participants enrolled in the Type 1 Diabetes Intelligence cohort, 6722 total were followed up to age 15 years or until onset of type 1 diabetes. Type 1 diabetes developed by age 15 years in 672 children, but did not develop in 6050 children. Optimal screening ages for two measurements were 2 years and 6 years, yielding sensitivity of 82% (95% CI 79–86) and PPV of 79% (95% CI 75–80) for diabetes by age 15 years. Autoantibody positivity at the beginning of each test age was highly predictive of diagnosis in the subsequent 2–5·99 year or 6–15-year age intervals. Autoantibodies usually appeared before age 6 years even in children diagnosed with diabetes much later in childhood. Interpretation: Our results show that initial screening for islet autoantibodies at two ages (2 years and 6 years) is sensitive and efficient for public health translation but might require adjustment by country on the basis of population-specific disease characteristics. Funding: Juvenile Diabetes Research Foundation.
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| 5. |
- Li, Ying, et al.
(författare)
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Predicting Type 1 Diabetes Onset using Novel Survival Analysis with Biomarker Ontology
- 2020
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Ingår i: AMIA ... Annual Symposium proceedings. AMIA Symposium. - 1942-597X. ; 2020, s. 727-736
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Tidskriftsartikel (refereegranskat)abstract
- Type 1 diabetes (T1D) is a chronic autoimmune disease that affects about 1 in 300 children and up to 1 in 100 adults during their life-time1. Improvements in early prediction of T1D onset may help prevent diagnosis for diabetic ketoacidosis, a serious complication often associated with a missed or delayed T1D diagnosis. In addition to genetic factors, progression to T1D is strongly associated with immunologic factors that can be measured during clinical visits. We developed a T1D-specific ontology that captures the dynamic patterns of these biomarkers and used it together with a survival model, RankSvx, proposed in our prior work2. We applied this approach to a T1D dataset harmonized from three birth cohort studies from the United States, Finland, and Sweden. Results show that the dynamic biomarker patterns captured in the proposed ontology are able to improve prediction performance (in concordance index) by 5.3%, 3.3%, 2.8%, and 1.0% over baseline for 3, 6, 9, and 12 month duration windows, respectively.
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