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- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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- Nilsen, M. S., et al.
(författare)
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3-Hydroxyisobutyrate, A Strong Marker of Insulin Resistance in Type 2 Diabetes and Obesity That Modulates White and Brown Adipocyte Metabolism
- 2020
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 69:9, s. 1903-1916
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Tidskriftsartikel (refereegranskat)abstract
- Circulating branched-chain amino acids (BCAAs) associate with insulin resistance and type 2 diabetes. 3-Hydroxyisobutyrate (3-HIB) is a catabolic intermediate of the BCAA valine. In this study, we show that in a cohort of 4,942 men and women, circulating 3-HIB is elevated according to levels of hyperglycemia and established type 2 diabetes. In complementary cohorts with measures of insulin resistance, we found positive correlates for circulating 3-HIB concentrations with HOMA2 of insulin resistance, as well as a transient increase in 3-HIB followed by a marked decrease after bariatric surgery and weight loss. During differentiation, both white and brown adipocytes upregulate BCAA utilization and release increasing amounts of 3-HIB. Knockdown of the 3-HIB-forming enzyme 3-hydroxyisobutyryl-CoA hydrolase decreases release of 3-HIB and lipid accumulation in both cell types. Conversely, addition of 3-HIB to white and brown adipocyte cultures increases fatty acid uptake and modulated insulin-stimulated glucose uptake in a time-dependent manner. Finally, 3-HIB treatment decreases mitochondrial oxygen consumption and generation of reactive oxygen species in white adipocytes, while increasing these measures in brown adipocytes. Our data establish 3-HIB as a novel adipocyte-derived regulator of adipocyte subtype-specific functions strongly linked to obesity, insulin resistance, and type 2 diabetes.
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| 7. |
- Jersin, R. A., et al.
(författare)
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Role of the Neutral Amino Acid Transporter SLC7A10 in Adipocyte Lipid Storage, Obesity, and Insulin Resistance
- 2021
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 70:3, s. 680-695
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Tidskriftsartikel (refereegranskat)abstract
- Elucidation of mechanisms that govern lipid storage, oxidative stress, and insulin resistance may lead to improved therapeutic options for type 2 diabetes and other obesity-related diseases. Here, we find that adipose expression of the small neutral amino acid transporter SLC7A10, also known as alanine-serine-cysteine transporter-1 (ASC-1), shows strong inverse correlates with visceral adiposity, insulin resistance, and adipocyte hypertrophy across multiple cohorts. Concordantly, loss of Slc7a10 function in zebrafish in vivo accelerates diet-induced body weight gain and adipocyte enlargement. Mechanistically, SLC7A10 inhibition in human and murine adipocytes decreases adipocyte serine uptake and total glutathione levels and promotes reactive oxygen species (ROS) generation. Conversely, SLC7A10 overexpression decreases ROS generation and increases mitochondrial respiratory capacity. RNA sequencing revealed consistent changes in gene expression between human adipocytes and zebrafish visceral adipose tissue following loss of SLC7A10, e.g., upregulation of SCD (lipid storage) and downregulation of CPT1A (lipid oxidation). Interestingly, ROS scavenger reduced lipid accumulation and attenuated the lipid-storing effect of SLC7A10 inhibition. These data uncover adipocyte SLC7A10 as a novel important regulator of adipocyte resilience to nutrient and oxidative stress, in part by enhancing glutathione levels and mitochondrial respiration, conducive to decreased ROS generation, lipid accumulation, adipocyte hypertrophy, insulin resistance, and type 2 diabetes.
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| 8. |
- Brasky, Theodore M., et al.
(författare)
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Dietary omega-3 fatty acids and endometrial cancer risk in the Epidemiology of Endometrial Cancer Consortium : An individual-participant meta-analysis
- 2023
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Ingår i: Gynecologic Oncology. - : Elsevier. - 0090-8258 .- 1095-6859. ; 169, s. 137-146
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Tidskriftsartikel (refereegranskat)abstract
- Background. Limited data from prospective studies suggest that higher dietary intake of long-chain omega-3 polyunsaturated fatty acids (LCn3PUFA), which hold anti-inflammatory properties, may reduce endometrial can-cer risk; particularly among certain subgroups characterized by body mass and tumor pathology.Materials and methods. Data from 12 prospective cohort studies participating in the Epidemiology of Endome-trial Cancer Consortium were harmonized as nested case-control studies, including 7268 endometrial cancer cases and 26,133 controls. Habitual diet was assessed by food frequency questionnaire, from which fatty acid in-takes were estimated. Two-stage individual-participant data mixed effects meta-analysis estimated adjusted odds ratios (OR) and 95% confidence intervals (CI) through logistic regression for associations between study -specific energy-adjusted quartiles of LCn3PUFA and endometrial cancer risk.Results. Women with the highest versus lowest estimated dietary intakes of docosahexaenoic acid, the most abundant LCn3PUFA in diet, had a 9% increased endometrial cancer risk (Quartile 4 vs. Quartile 1: OR 1.09, 95% CI: 1.01-1.19; P trend = 0.04). Similar elevated risks were observed for the summary measure of total LCn3PUFA (OR 1.07, 95% CI: 0.99-1.16; P trend = 0.06). Stratified by body mass index, higher intakes of LCn3PUFA were as-sociated with 12-19% increased endometrial cancer risk among overweight/obese women and no increased risk among normal-weight women. Higher associations appeared restricted to White women. The results did not dif-fer by cancer grade.Conclusion. Higher dietary intakes of LCn3PUFA are unlikely to reduce endometrial cancer incidence; rather, they may be associated with small to moderate increases in risk in some subgroups of women, particularly over-weight/obese women.(c) 2022 Elsevier Inc. All rights reserved.
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| 9. |
- Brenner, M, et al.
(författare)
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Development of the key performance indicators for digital health interventions: A scoping review
- 2023
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Ingår i: Digital health. - : SAGE Publications. - 2055-2076. ; 9, s. 20552076231152160-
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Tidskriftsartikel (refereegranskat)abstract
- Digital health interventions offer new methods for delivering healthcare, with the potential to innovate healthcare services. Key performance indicators play a role in the evaluation, measurement, and improvement in healthcare quality and service performance. The aim of this scoping review was to identify current knowledge and evidence surrounding the development of key performance indicators for digital health interventions. Methods A literature search was conducted across ten key databases: AMED – The Allied and Complementary Medicine Database, CINAHL – Complete, Health Source: Nursing/Academic Edition, MEDLINE, APA PsycINFO, EMBASE, EBM Reviews – Cochrane Database of Systematic Reviews, EBM Reviews – Database of Abstracts of Reviews of Effects, EBM Reviews – Health Technology Assessment, and IEEE Xplore. Results Five references were eligible for the review. Two were articles on original research studies of a specific digital health intervention, and two were overviews of methods for developing digital health interventions (not specific to a single digital health intervention). All the included reports discussed the involvement of stakeholders in developing key performance indicators for digital health interventions. The step of identifying and defining the key performance indicators was completed using various methodologies, but all centred on a form of stakeholder involvement. Potential options for stakeholder involvement for key performance indicator identification include the use of an elicitation framework, a factorial survey approach, or a Delphi study. Conclusions Few articles were identified, highlighting a significant gap in evidence-based knowledge in this domain. All the included articles discussed the involvement of stakeholders in developing key performance indicators for digital health interventions, which were performed using various methodologies. The articles acknowledged a lack of literature related to key performance indicator development for digital health interventions. To allow comparability between key performance indicator initiatives and facilitate work in the field, further research would be beneficial to develop a common methodology for key performance indicators development for digital health interventions.
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| 10. |
- Brenner, M, et al.
(författare)
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Development of the key performance indicators for digital health interventions: A scoping review
- 2023
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Ingår i: Digital health. - : SAGE Publications. - 2055-2076. ; 9, s. 20552076231152160-
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Tidskriftsartikel (refereegranskat)abstract
- Digital health interventions offer new methods for delivering healthcare, with the potential to innovate healthcare services. Key performance indicators play a role in the evaluation, measurement, and improvement in healthcare quality and service performance. The aim of this scoping review was to identify current knowledge and evidence surrounding the development of key performance indicators for digital health interventions. Methods A literature search was conducted across ten key databases: AMED – The Allied and Complementary Medicine Database, CINAHL – Complete, Health Source: Nursing/Academic Edition, MEDLINE, APA PsycINFO, EMBASE, EBM Reviews – Cochrane Database of Systematic Reviews, EBM Reviews – Database of Abstracts of Reviews of Effects, EBM Reviews – Health Technology Assessment, and IEEE Xplore. Results Five references were eligible for the review. Two were articles on original research studies of a specific digital health intervention, and two were overviews of methods for developing digital health interventions (not specific to a single digital health intervention). All the included reports discussed the involvement of stakeholders in developing key performance indicators for digital health interventions. The step of identifying and defining the key performance indicators was completed using various methodologies, but all centred on a form of stakeholder involvement. Potential options for stakeholder involvement for key performance indicator identification include the use of an elicitation framework, a factorial survey approach, or a Delphi study. Conclusions Few articles were identified, highlighting a significant gap in evidence-based knowledge in this domain. All the included articles discussed the involvement of stakeholders in developing key performance indicators for digital health interventions, which were performed using various methodologies. The articles acknowledged a lack of literature related to key performance indicator development for digital health interventions. To allow comparability between key performance indicator initiatives and facilitate work in the field, further research would be beneficial to develop a common methodology for key performance indicators development for digital health interventions.
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