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- Ahlqvist, E., et al.
(författare)
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Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables
- 2018
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Ingår i: Lancet Diabetes & Endocrinology. - : Elsevier BV. - 2213-8587. ; 6:5, s. 361-369
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Tidskriftsartikel (refereegranskat)abstract
- Background Diabetes is presently classified into two main forms, type 1 and type 2 diabetes, but type 2 diabetes in particular is highly heterogeneous. A refined classification could provide a powerful tool to individualise treatment regimens and identify individuals with increased risk of complications at diagnosis. Methods We did data-driven cluster analysis (k-means and hierarchical clustering) in patients with newly diagnosed diabetes (n=8980) from the Swedish All New Diabetics in Scania cohort. Clusters were based on six variables (glutamate decarboxylase antibodies, age at diagnosis, BMI, HbA(1c), and homoeostatic model assessment 2 estimates of beta-cell function and insulin resistance), and were related to prospective data from patient records on development of complications and prescription of medication. Replication was done in three independent cohorts: the Scania Diabetes Registry (n=1466), All New Diabetics in Uppsala (n=844), and Diabetes Registry Vaasa (n=3485). Cox regression and logistic regression were used to compare time to medication, time to reaching the treatment goal, and risk of diabetic complications and genetic associations. Findings We identified five replicable clusters of patients with diabetes, which had significantly different patient characteristics and risk of diabetic complications. In particular, individuals in cluster 3 (most resistant to insulin) had significantly higher risk of diabetic kidney disease than individuals in clusters 4 and 5, but had been prescribed similar diabetes treatment. Cluster 2 (insulin deficient) had the highest risk of retinopathy. In support of the clustering, genetic associations in the clusters differed from those seen in traditional type 2 diabetes. Interpretation We stratified patients into five subgroups with differing disease progression and risk of diabetic complications. This new substratification might eventually help to tailor and target early treatment to patients who would benefit most, thereby representing a first step towards precision medicine in diabetes.
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- Luukkonen, Panu K., et al.
(författare)
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Impaired hepatic lipid synthesis from polyunsaturated fatty acids in TM6SF2 E167K variant carriers with NAFLD
- 2017
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Ingår i: Journal of Hepatology. - : Elsevier. - 0168-8278 .- 1600-0641. ; 67:1, s. 128-136
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Tidskriftsartikel (refereegranskat)abstract
- Background: Carriers of the transmembrane 6 superfamily member 2 E167K gene variant (TM6SF2(EK/KK)) have decreased expression of the TM6SF2 gene and increased risk of NAFLD and NASH. Unlike common 'obese/metabolic' NAFLD, these subjects lack hypertriglyceridemia and have lower risk of cardiovascular disease. In animals, phosphatidylcholine (PC) deficiency results in a similar phenotype. PCs surround the core of VLDL consisting of triglycerides (TGs) and cholesteryl-esters (CEs). We determined the effect of the TM6SF2 E167K on these lipids in the human liver and serum and on hepatic gene expression and studied the effect of TM6SF2 knockdown on hepatocyte handling of these lipids.Methods: Liver biopsies were taken from subjects characterized with respect to the TM6SF2 genotype, serum and liver lipidome, gene expression and histology. In vitro, after TM6SF2 knockdown in HuH-7 cells, we compared incorporation of different fatty acids into TGs, CEs, and PCs.Results: The TM6SF2(EK/KK) and TM6SF2EE groups had similar age, gender, BMI and HOMA-IR. Liver TGs and CEs were higher and liver PCs lower in the TM6SF2(EK/KK) than the TM6SF2EE group (p<0.05). Polyunsaturated fatty acids (PUFA) were deficient in liver and serum TGs and liver PCs but hepatic free fatty acids were relatively enriched in PUFA (p<0.05). Incorporation of PUFA into TGs and PCs in TM6SF2 knockdown hepatocytes was decreased (p< 0.05). Hepatic expression of TM6SF2 was decreased in variant carriers, and was co-expressed with genes regulated by PUFAs.Conclusions: Hepatic lipid synthesis from PUFAs is impaired and could contribute to deficiency in PCs and increased intrahepatic TG in TM6SF2 E167K variant carriers. (C) 2017 European Association for the Study of the Liver.
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| 14. |
- Fallara, G., et al.
(författare)
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Time on treatment with abiraterone and enzalutamide in the Patient-overview Prostate Cancer in The National Prostate Cancer Register of Sweden
- 2021
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 60:12, s. 1589-1596
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Tidskriftsartikel (refereegranskat)abstract
- Background There are little and inconsistent data from clinical practice on time on treatment with the androgen receptor-targeted drugs (ART) abiraterone and enzalutamide in men with metastatic castration-resistant prostate cancer (mCRPC). We assessed time on treatment with ART and investigated predictors of time on treatment. Material and methods Time on treatment with ART in men with mCRPC in the patient-overview prostate cancer (PPC), a subregister of the National Prostate Cancer Register (NPCR) of Sweden, was assessed by use of Kaplan-Meier plots and Cox regression. To assess the representativity of PPC for time on treatment, a comparison was made with all men in NPCR who had a filling for ART in the Prescribed Drug Registry. Results 2038 men in PPC received ART between 2015 and 2019. Median time on treatment in chemo-naive men was 10.8 (95% confidence interval 9.1-13.1) months for abiraterone and 14.1 (13.5-15.5) for enzalutamide. After the use of docetaxel, time on treatment was 8.2 (6.5-12.4) months for abiraterone and 11.1 (9.8-12.6) for enzalutamide. Predictors of a long time on treatment with ART were long duration of ADT prior to ART, low serum levels of PSA at start of ART, absence of visceral metastasis, good performance status, and no prior use of docetaxel. PPC captured 2522/6337 (40%) of all men in NPCR who had filled a prescription for ART. Based on fillings in the Prescribed Drug Registry, men in PPC had a slightly longer median time on treatment with ART compared to all men in NPCR, 9.6 (9.1-10.3) vs. 8.6 (6.3-9.1) months. Conclusions Time on treatment in clinical practice was similar or shorter than that in published RCTs, due to older age, poorer performance status and more comorbidities.
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- George, G., et al.
(författare)
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Risk of cardiovascular events in men on abiraterone or enzalutamide combined with GnRH agonists: nation-wide, population-based cohort study in Sweden
- 2021
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 60:4, s. 459-465
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Tidskriftsartikel (refereegranskat)abstract
- Background Men with prostate cancer (PCa) on gonadotropin-releasing hormone agonists (GnRH) have an increased risk of cardiovascular disease (CVD) compared to men with PCa not on GnRH as well as compared with PCa-free men. Whether the addition of androgen receptor targeted (ART) drugs to GnRH further increases CVD risk, remains to be fully elucidated. Material and methods We investigated risk of CVD for men with castration resistant PCa (CRPC) on GnRH plus ART; abiraterone or enzalutamide vs 5,127 and 12,079 respective matched comparator men on GnRH in Prostate Cancer data Base Sweden (PCBaSeTraject) 4.1 between 1 June 2015 and 31 December 2018. PCBaSeTraject links National Prostate Cancer Register of Sweden to other healthcare registries and demographic databases. We conducted multivariable Cox proportional hazard models adjusting for PCa risk category, Charlson comorbidity index (CCI), insulin or statin use, civil status, level of education, history of CVD events and number of CVD drugs, with any incident or fatal CVD as the outcome. Results and conclusion 1,310 men were treated with abiraterone and 3,579 with enzalutamide. In multivariable analysis, CVD risk was increased in men on abiraterone (hazard ratio (HR): 1.19; 95% confidence interval (CI): 1.03-1.38) and in men on enzalutamide (HR: 1.10; 95% CI: 1.01-1.20). Men with a recent CVD (<12 months) including both men on ART as well as comparators had a much higher probability of a new CVD vs men with no prior CVD. CVD risk was mildly increased in men with PCa on GnRH plus abiraterone or enzalutamide vs comparator men on GnRH. Residual confounding and detection bias may at least partly explain this association.
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| 16. |
- Mellin, P., et al.
(författare)
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Environmental and safety aspects of AM metal powder recycling
- 2019
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Ingår i: Euro PM 2019 Congress and Exhibition.
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Konferensbidrag (refereegranskat)abstract
- Repeated recirculation of powder in AM processes ultimately results in a powder with degraded properties. We firstly discuss this topic and describe an experiment designed to understand the mechanisms behind the degradation. Secondly, we perform yield analysis for build jobs on a SLM 125 at RISE IVF. Further on, we consider the required resources and estimate the emitted carbon dioxide equivalents (kgCO2eq) during production of the PBF-LB fraction of two gas atomized powders. The first powder is a tool steel alloy that emits 3.1 kgCO2eq/kg; the second powder is Hastelloy X (HX) that emits 24.2 kgCO2eq/kg. The HX powder, if degraded, is hence very desirable to recycle. Producing 1 kg of PBF-LB fraction from recycled HX material causes 5.7 kgCO2eq vs 24.2 from virgin sources. Finally, we review the health and safety aspects of recirculation and recycling of powder.
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