| 21. |
- Eriksson, Jan W, et al.
(författare)
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Tissue-specific glucose partitioning and fat content in prediabetes and type 2 diabetes: whole-body PET/MRI during hyperinsulinemia
- 2021
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Ingår i: European journal of endocrinology. - : Bioscientifica. - 0804-4643 .- 1479-683X. ; 184:6, s. 879-899
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To obtain direct quantifications of glucose turnover, volumes an d fat content of several tissues in the development of type 2 diabetes (T2D) using a novel integrated a pproach for whole-body imaging. Design and methods: Hyperinsulinemic-euglycemic clamps and simultaneous whole-body integrated [18F]FDG-PET/MRI with automated analyses were performed in control (n = 12), prediabetes (n = 16) and T2D (n = 13) subjects matched for age, sex and BMI. Results: Whole-body glucose uptake (Rd) was reduced by approximately 25% in T2D vs control subjects, and partitioning to brain was increased from 3.8% of total Rd in co ntrols to 7.1% in T2D. In liver, subcutaneous AT, thigh muscle, total tissue glucose metabolic rates (MRglu) and their % of total Rd were reduced in T2D compared to contr ol subjects. The prediabetes group had intermediate findings. Total MRglu in heart, visceral AT, gluteus and calf muscle was similar across groups. Whole-body insulin sensitivity asses sed as glucose infusion rate correlated with liver MR glu but inversely with brain MRglu. Liver fat content correlated with MRglu in brain but inversely with MRglu in other tissues. Calf muscle fat was inversely associated with MR glu only in the same muscle group. Conclusions: This integrated imaging approach provides detailed quantification of tissue-specific glucose metabolism. During T2D development, insulin-stimulated glucose disposal is impaired and increasingly shifted away from muscle, liver and fat toward the brain. Altered glucose handling in the brain and liver fat accumulation may aggravate insulin resistance in several organs. © 2021 BioScientifica Ltd.. All rights reserved.
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| 22. |
- Guglielmo, Priscilla, et al.
(författare)
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Validation of automated whole-body analysis of metabolic and morphological parameters from an integrated FDG-PET/MRI acquisition
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Automated quantification of tissue morphology and tracer uptake in PET/MR images could streamline the analysis compared to traditional manual methods. To validate a single atlas image segmentation approach for automated assessment of tissue volume, fat content (FF) and glucose uptake (GU) from whole-body [18F]FDG-PET/MR images. Twelve subjects underwent whole-body [18F]FDG-PET/MRI during hyperinsulinemic-euglycemic clamp. Automated analysis of tissue volumes, FF and GU were achieved using image registration to a single atlas image with reference segmentations of 18 volume of interests (VOIs). Manual segmentations by an experienced radiologist were used as reference. Quantification accuracy was assessed with Dice scores, group comparisons and correlations. VOI Dice scores ranged from 0.93 to 0.32. Muscles, brain, VAT and liver showed the highest scores. Pancreas, large and small intestines demonstrated lower segmentation accuracy and poor correlations. Estimated tissue volumes differed significantly in 8 cases. Tissue FFs were often slightly but significantly overestimated. Satisfactory agreements were observed in most tissue GUs. Automated tissue identification and characterization using a single atlas segmentation performs well compared to manual segmentation in most tissues and will be valuable in future studies. In certain tissues, alternative quantification methods or improvements to the current approach is needed.
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| 23. |
- Kamble, Prasad G., et al.
(författare)
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Proof-of-concept for CRISPR/Cas9 gene editing in human preadipocytes : Deletion of FKBP5 and PPARG and effects on adipocyte differentiation and metabolism
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- CRISPR/Cas9 has revolutionized the genome-editing field. So far, successful application in human adipose tissue has not been convincingly shown. We present a method for gene knockout using electroporation in preadipocytes from human adipose tissue that achieved at least 90% efficiency without any need for selection of edited cells or clonal isolation. We knocked out the FKBP5 and PPARG genes in preadipocytes and studied the resulting phenotypes. PPARG knockout prevented differentiation into adipocytes. Conversely, deletion of FKBP51, the protein coded by the FKBP5 gene, did not affect adipogenesis. Instead, it markedly modulated glucocorticoid effects on adipocyte glucose metabolism and, furthermore, we show some evidence of altered transcriptional activity of glucocorticoid receptors. This has potential implications for the development of insulin resistance and type 2 diabetes. The reported method is simple, easy to adapt, and enables the use of human primary preadipocytes instead of animal adipose cell models to assess the role of key genes and their products in adipose tissue development, metabolism and pathobiology.
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| 24. |
- Katsogiannos, Petros, 1979-, et al.
(författare)
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Changes in Circulating Cytokines and Adipokines After RYGB in Patients with and without Type 2 Diabetes
- 2021
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Ingår i: Obesity. - : Wiley. - 1930-7381 .- 1930-739X. ; 29:3, s. 535-542
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveThis study aimed to compare cytokine and adipokine levels in patients with obesity with and without type 2 diabetes (T2D) at baseline and 6 months after Roux‐en‐Y gastric bypass (RYGB) with healthy controls.MethodsA total of 34 patients (21 with T2D) with BMI of 30 to 45 kg/m2 were compared with 25 healthy controls without obesity. Cytokines, adipokines, and peptides of relevance for inflammation and metabolism were analyzed in plasma.ResultsSignificant decreases in weight and glycated hemoglobin A1c were observed. At baseline, interleukin‐6 (IL‐6), IFN‐β, IL‐18, leptin, and hepatocyte growth factor were higher in all patients with obesity compared with healthy controls. In patients without T2D, TNF‐α, IL‐1α, IL‐2, IL‐15, and visfatin were also increased, whereas bone morphogenic protein‐4 was decreased. Following RYGB, IL‐6 and hepatocyte growth factor were still increased in both groups compared with controls. In T2D patients, IFN‐β, IL‐27, IL‐1α, IL‐2, regenerating islet‐derived protein 3A, visfatin, and osteopontin were found to be increased. In patients without T2D, TNF‐α, IL‐1α, IL‐2, IL‐15, leptin, and visfatin remained increased.ConclusionsThe altered cytokine profile of patients with obesity persisted after RYGB despite large weight loss and improved metabolic status, thus reflecting an inherent inflammatory state.
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| 25. |
- Katsogiannos, Petros, et al.
(författare)
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Rapid changes in neuroendocrine regulation may contribute to reversal of type 2 diabetes after gastric bypass surgery
- 2020
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Ingår i: Endocrine. - : SPRINGER. - 1355-008X .- 1559-0100. ; 67:2, s. 344-353
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To explore the role of hormones and the autonomic nervous system in the rapid remission of diabetes after Roux-en-Y Gastric Bypass (RYGB).Research design and methods: Nineteen obese patients with type 2 diabetes, 7 M/12 F, were randomized (2:1) to RYGB or standard-of-care medical treatment (control). At baseline and 4 and 24 weeks post surgery, fasting blood sampling, OGTT, intravenous arginine challenge, and heart-rate variability (HRV) assessments were performed.Results: At both 4 and 24 weeks post-RYGB the following effects were found: arginine-stimulated insulin secretion was reduced. GLP-1, GIP, and glucagon rise during OGTT was enhanced. IGF-1 and GH levels increased. In addition, total HRV and spectral components P-LF (power of low frequency) and P-HF (power of high frequency) increased. At 4 weeks, morning cortisol was lower than baseline and 24 weeks. At 24 weeks, NEFA levels during OGTT, and the P-LF/P-HF ratio decreased. None of these changes were seen in the control group.Conclusions: There were rapid changes within 4 weeks after RYGB: signs of enhanced parasympathetic nerve activity, reduced morning cortisol, and enhanced incretin and glucagon responses to glucose. The findings suggest that neurohormonal mechanisms can contribute to the rapid improvement of insulin resistance and glycemia following RYGB in type 2 diabetes.
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| 26. |
- Lundqvist, Martin H., et al.
(författare)
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Altered hormonal and autonomic nerve responses to hypo- and hyperglycaemia are found in overweight and insulin-resistant individuals and may contribute to the development of type 2 diabetes
- 2021
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Ingår i: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 64:3, s. 641-655
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis: Results from animal models and some clinical work suggest a role for the central nervous system (CNS) in glucose regulation and type 2 diabetes pathogenesis by modulation of glucoregulatory hormones and the autonomic nervous system (ANS). The aim of this study was to characterise the neuroendocrine response to various glucose concentrations in overweight and insulin-resistant individuals compared with lean individuals.Methods: Overweight/obese (HI, n = 15, BMI ≥27.0 kg/m2) and lean (LO, n = 15, BMI <27.0 kg/m2) individuals without diabetes underwent hyperinsulinaemic euglycaemic–hypoglycaemic clamps and hyperglycaemic clamps on two separate occasions with measurements of hormones, Edinburgh Hypoglycaemic Symptom Scale (ESS) score and heart rate variability (HRV). Statistical methods included groupwise comparisons with Mann–Whitney U tests, multilinear regressions and linear mixed models between neuroendocrine responses and continuous metabolic variables.Results: During hypoglycaemic clamps, there was an elevated cortisol response in HI vs LO (median ΔAUC 12,383 vs 4793 nmol/l × min; p = 0.050) and a significantly elevated adrenocorticotropic hormone (ACTH) response in HI vs LO (median ΔAUC 437.3 vs 162.0 nmol/l × min; p = 0.021). When adjusting for clamp glucose levels, obesity (p = 0.033) and insulin resistance (p = 0.009) were associated with elevated glucagon levels. By contrast, parasympathetic activity was less suppressed in overweight individuals at the last stage of hypoglycaemia compared with euglycaemia (high-frequency power of HRV, p = 0.024). M value was the strongest predictor for the ACTH and PHF responses, independent of BMI and other variables. There was a BMI-independent association between the cortisol response and ESS score response (p = 0.024). During hyperglycaemic clamps, overweight individuals displayed less suppression of glucagon levels (median ΔAUC −63.4% vs −73.0%; p = 0.010) and more suppression of sympathetic relative to parasympathetic activity (low-frequency/high-frequency power, p = 0.011).Conclusions/interpretation: This study supports the hypothesis that altered responses of insulin-antagonistic hormones and the ANS to glucose fluctuations occur in overweight and insulin-resistant individuals, and that these responses are probably partly mediated by the CNS. Their potential role in development of type 2 diabetes needs to be addressed in future research.
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| 27. |
- Michelet, Mona, et al.
(författare)
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Associations between unmet needs for daytime activities and company and scores on the Neuropsychiatric Inventory-Questionnaire in people with dementia : a longitudinal study
- 2021
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Ingår i: Aging & Mental Health. - : Informa UK Limited. - 1360-7863 .- 1364-6915. ; 26:4, s. 725-734
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES To examine prospectively the association between unmet needs for daytime activities and company and behavioural and psychological symptoms of dementia.METHODS We included 451 people with mild or moderate dementia, from eight European countries, who were assessed three times over 12 months. Unmet needs were measured with the Camberwell Assessment of Need for the Elderly. Three sub-syndromes of the Neuropsychiatric Inventory-Questionnaire were regressed, one-by-one, against unmet needs for daytime activities and company, adjusting for demographic and clinical-functional covariates.RESULTS Unmet needs for daytime activities were associated with more affective symptoms at baseline, six and twelve months, mean 0.74 (p < 0.001), 0.76 (p < 0.001) and 0.78 (p = 0.001) points higher score respectively, and with more psychotic symptoms at baseline (mean 0.39 points, p = 0.007) and at six months follow-up (mean 0.31 points, p = 0.006). Unmet needs for company were associated with more affective symptoms at baseline, six and twelve months, mean 0.44 (p = 0.033), 0.67 (p < 0.001) and 0.91 (p < 0.001) points higher score respectively, and with more psychotic symptoms at baseline (mean 0.40 points, p = 0.005) and at six months (mean 0.35 points, p = 0.002) follow-up.CONCLUSION Interventions to reduce unmet needs for daytime activities and company could reduce affective and psychotic symptoms in people with dementia.
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| 28. |
- Morawska, Lidia, et al.
(författare)
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The state of science on severe air pollution episodes : Quantitative and qualitative analysis
- 2021
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Ingår i: Environment International. - : Elsevier BV. - 1873-6750 .- 0160-4120. ; 156, s. 106732-106732
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Tidskriftsartikel (refereegranskat)abstract
- Severe episodic air pollution blankets entire cities and regions and have a profound impact on humans and their activities. We compiled daily fine particle (PM2.5) data from 100 cities in five continents, investigated the trends of number, frequency, and duration of pollution episodes, and compared these with the baseline trend in air pollution. We showed that the factors contributing to these events are complex; however, long-term measures to abate emissions from all anthropogenic sources at all times is also the most efficient way to reduce the occurrence of severe air pollution events. In the short term, accurate forecasting systems of such events based on the meteorological conditions favouring their occurrence, together with effective emergency mitigation of anthropogenic sources, may lessen their magnitude and/or duration. However, there is no clear way of preventing events caused by natural sources affected by climate change, such as wildfires and desert dust outbreaks.
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| 29. |
- Nakanishi, Tomoko, et al.
(författare)
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Age-dependent impact of the major common genetic risk factor for COVID-19 on severity and mortality
- 2021
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Ingår i: Journal of Clinical Investigation. - : American Society For Clinical Investigation. - 0021-9738 .- 1558-8238. ; 131:23
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND. There is considerable variability in COVID-19 outcomes among younger adults, and some of this variation may be due to genetic predisposition. METHODS. We combined individual level data from 13,888 COVID-19 patients (n = 7185 hospitalized) from 17 cohorts in 9 countries to assess the association of the major common COVID-19 genetic risk factor (chromosome 3 locus tagged by rs10490770) with mortality, COVID-19-related complications, and laboratory values. We next performed metaanalyses using FinnGen and the Columbia University COVID-19 Biobank. RESULTS. We found that rs10490770 risk allele carriers experienced an increased risk of all-cause mortality (HR, 1.4; 95% CI, 1.2-1.7). Risk allele carriers had increased odds of several COVID-19 complications: severe respiratory failure (OR, 2.1; 95% CI, 1.6-2.6), venous thromboembolism (OR, 1.7; 95% CI, 1.2-2.4), and hepatic injury (OR, 1.5; 95% CI, 1.2-2.0). Risk allele carriers age 60 years and younger had higher odds of death or severe respiratory failure (OR, 2.7; 95% CI, 1.8-3.9) compared with those of more than 60 years (OR, 1.5; 95% CI, 1.2-1.8; interaction, P = 0.038). Among individuals 60 years and younger who died or experienced severe respiratory failure, 32.3% were risk-variant carriers compared with 13.9% of those not experiencing these outcomes. This risk variant improved the prediction of death or severe respiratory failure similarly to, or better than, most established clinical risk factors. CONCLUSIONS. The major common COVID-19 genetic risk factor is associated with increased risks of morbidity and mortality, which are more pronounced among individuals 60 years or younger. The effect was similar in magnitude and more common than most established clinical risk factors, suggesting potential implications for future clinical risk management.
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| 30. |
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