| 1. |
- Neiman, Daniel, et al.
(författare)
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Multiplexing DNA methylation markers to detect circulating cell-free DNA derived from human pancreatic β cells
- 2020
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Ingår i: JCI Insight. - : American Society for Clinical Investigation. - 2379-3708. ; 5:14
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Tidskriftsartikel (refereegranskat)abstract
- It has been proposed that unmethylated insulin promoter fragments in plasma derive exclusively from β cells, reflect their recent demise, and can be used to assess β cell damage in type 1 diabetes. Herein we describe an ultrasensitive assay for detection of a β cell–specific DNA methylation signature, by simultaneous assessment of 6 DNA methylation markers, that identifies β cell DNA in mixtures containing as little as 0.03% β cell DNA (less than 1 β cell genome equivalent). Based on this assay, plasma from nondiabetic individuals (N = 218, aged 4–78 years) contained on average only 1 β cell genome equivalent/mL. As expected, cell-free DNA (cfDNA) from β cells was significantly elevated in islet transplant recipients shortly after transplantation. We also detected β cell cfDNA in a patient with KATP congenital hyperinsulinism, in which substantial β cell turnover is thought to occur. Strikingly, in contrast to previous reports, we observed no elevation of β cell–derived cfDNA in autoantibody-positive subjects at risk for type 1 diabetes (N = 32), individuals with recent-onset type 1 diabetes (<4 months, N = 92), or those with long-standing disease (>4 months, N = 38). We discuss the utility of sensitive β cell cfDNA analysis and potential explanations for the lack of a β cell cfDNA signal in type 1 diabetes.
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| 2. |
- Sundberg, Frida, et al.
(författare)
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A decade of improved glycemic control in young children with type 1 diabetes: A population-based cohort study
- 2021
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Ingår i: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 22:5, s. 742-748
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Tidskriftsartikel (refereegranskat)abstract
- Background: Early-onset type 1 diabetes (T1D) is associated with high risk of early cardiovascular complications and premature death. The strongest modifiable risk factor is HbA1c. Other modifiable factors, such as overweight, also increase the risk of complications. During the last decade, the introduction of continuous glucose monitoring (CGM) has offered new options in the treatment of T1D. Objective: To compare treatment outcomes in children younger than 7 years with T1D in Sweden in two separate cohorts: one in 2008 and one in 2018. Methods: All children in the national pediatric diabetes registry (SWEDIABKIDS) younger than 7 years with T1D were included. Data from 2008 and 2018 were analyzed. Results: Data were available on 666 children (45% girls) in 2008 and 779 children (45% girls) in 2018. Mean age was 5.6 (1.4) versus 5.5 (1.4) years and mean diabetes duration 2.3 (1.4) versus 2.2 (1.4) years. The use of CGM increased from 0% to 98% and the use of an insulin pump from 40% in 2008 to 82% (p < 0.01)in 2018.Mean HbA1c was 58 mmol/mol (7.4%) in 2008 and 50 mmol/mol (6.7%) in 2018 (p < 0.01). The frequency of overweight and obesity was the same in 2008 and 2018(26% vs. 29%). Conclusion: During this decade, usage of CGM and insulin pump increased and HbA1c decreased. However, HbA1c remained higher than the physiological level and thus continued to represent a cardiovascular risk, especially in combination with overweight or obesity. The frequency of overweight and obesity remained unchanged. © 2021 The Authors. Pediatric Diabetes published by John Wiley & Sons Ltd.
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| 4. |
- Teixeira, Pedro F., et al.
(författare)
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Assisting the implementation of screening for type 1 diabetes by using artificial intelligence on publicly available data
- 2024
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Ingår i: DIABETOLOGIA. - : SPRINGER. - 0012-186X .- 1432-0428.
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Tidskriftsartikel (refereegranskat)abstract
- The type 1 diabetes community is coalescing around the benefits and advantages of early screening for disease risk. To be accepted by healthcare providers, regulatory authorities and payers, screening programmes need to show that the testing variables allow accurate risk prediction and that individualised risk-informed monitoring plans are established, as well as operational feasibility, cost-effectiveness and acceptance at population level. Artificial intelligence (AI) has the potential to contribute to solving these issues, starting with the identification and stratification of at-risk individuals. ASSET (AI for Sustainable Prevention of Autoimmunity in the Society; www.asset.healthcare) is a public/private consortium that was established to contribute to research around screening for type 1 diabetes and particularly to how AI can drive the implementation of a precision medicine approach to disease prevention. ASSET will additionally focus on issues pertaining to operational implementation of screening. The authors of this article, researchers and clinicians active in the field of type 1 diabetes, met in an open forum to independently debate key issues around screening for type 1 diabetes and to advise ASSET. The potential use of AI in the analysis of longitudinal data from observational cohort studies to inform the design of improved, more individualised screening programmes was also discussed. A key issue was whether AI would allow the research community and industry to capitalise on large publicly available data repositories to design screening programmes that allow the early detection of individuals at high risk and enable clinical evaluation of preventive therapies. Overall, AI has the potential to revolutionise type 1 diabetes screening, in particular to help identify individuals who are at increased risk of disease and aid in the design of appropriate follow-up plans. We hope that this initiative will stimulate further research on this very timely topic.
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| 5. |
- Temple, Alastair, et al.
(författare)
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Development of Experimental Method for Assessing Risk of Lithium Fires Related with Fusion Reactor Lithium Cooling Loops
- 2021
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this project is to provide the basis for risk assessments relating to the risk of lithium leaks in the DONES project. This report firstly summarizes the current knowledge of risks and reaction features at different scales with liquid lithium. Note that the review is limited to fire behaviour of lithium in its liquid state and does not consider additional risks connected with breeding tritium or corrosive effects of impurities. Some of the questions important for this project are to limit the lithium reaction with water, limit the spread of fire started by a reaction with lithium and extinguish flame of lithium induced fires. The second part of the report consists discussion of some initial small-scale experiments, undertaken to provide a basis for limiting the extent for further larger tests, and a proposal for an experimental device where lithium reactions can be studied in a controlled environment, i.e. with controlled amount of oxygen, nitrogen or humidity in the experiment. This will then be the basis for risk assessment for liquid lithium loop in the DONES facility.
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