| 1. |
- Antoniewicz, Lukasz, et al.
(författare)
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Electronic cigarettes increase endothelial progenitor cells in the blood of healthy volunteers
- 2016
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Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 255, s. 179-185
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: The use of electronic cigarettes is increasing dramatically on a global scale and its effects on human health remain uncertain. In the present study, we measured endothelial progenitor cells (EPCs) and microvesicles (MVs) in healthy young volunteers following short-term exposure to inhalation of e-cigarette vapor (ECV) to determine vascular changes.Methods: Sixteen healthy seldom smokers were randomized into two groups either exposed or not exposed to 10 puffs of ECV for 10 min, in a crossover design. Blood samples were obtained at baseline and 1, 4 and 24 h following exposure. EPCs (CD34 + CD309) and MVs were analyzed by flow cytometry. MVs were phenotyped according to origin (platelet (CD41), endothelial (CD144), leukocytes (CD45), monocytes (CD14)) and nuclear content (SYTO 13 dye). In addition, expression of inflammation markers such P-selectin (CD62P), E-selectin (CD62E), CD40-ligand (CD154) and HMGB1 was investigated. Fractional exhaled nitric oxide (FeNO) was also measured at baseline and after 24 h.Results: EPC levels in blood were significantly increased 1 h following exposure to ECV and returned to baseline values after 24 h. Only E-selectin positive MVs (endothelial origin) were slightly elevated (p < 0.038). FeNO was unaffected by exposure to ECV. Conclusions: In healthy volunteers, ten puffs of e-cigarette vapor inhalation caused an increase in EPCs. This increase was of the same magnitude as following smoking of one traditional cigarette, as we previously demonstrated. Taken together, these results may represent signs of possible vascular changes after short e-cigarette inhalation. Further studies analyzing potential cardiovascular health effects are critical as the e-cigarette market continues to burgeon.
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| 2. |
- Botvinik-Nezer, Rotem, et al.
(författare)
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Variability in the analysis of a single neuroimaging dataset by many teams
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 582, s. 84-88
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Tidskriftsartikel (refereegranskat)abstract
- Data analysis workflows in many scientific domains have become increasingly complex and flexible. Here we assess the effect of this flexibility on the results of functional magnetic resonance imaging by asking 70 independent teams to analyse the same dataset, testing the same 9 ex-ante hypotheses(1). The flexibility of analytical approaches is exemplified by the fact that no two teams chose identical workflows to analyse the data. This flexibility resulted in sizeable variation in the results of hypothesis tests, even for teams whose statistical maps were highly correlated at intermediate stages of the analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Notably, a meta-analytical approach that aggregated information across teams yielded a significant consensus in activated regions. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset(2-5). Our findings show that analytical flexibility can have substantial effects on scientific conclusions, and identify factors that may be related to variability in the analysis of functional magnetic resonance imaging. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for performing and reporting multiple analyses of the same data. Potential approaches that could be used to mitigate issues related to analytical variability are discussed. The results obtained by seventy different teams analysing the same functional magnetic resonance imaging dataset show substantial variation, highlighting the influence of analytical choices and the importance of sharing workflows publicly and performing multiple analyses.
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| 3. |
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| 4. |
- Kuhl, Jeanette, et al.
(författare)
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Metabolomics as a tool to evaluate exercise-induced improvements in insulin sensitivity
- 2008
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Ingår i: Metabolomics. - : Springer Boston. - 1573-3882 .- 1573-3890. ; 4:3, s. 273-82
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Tidskriftsartikel (refereegranskat)abstract
- Exercise affects substrate utilisation and insulin sensitivity, which in turn improve blood glucose and lipid levels in subjects with type 2 diabetes (T2D). However, making long-lasting lifestyle-changes might be more realistic if the results were easier to record. Screening for biomarkers reflecting metabolic fitness could thus serve as a tool for maintained motivation. The aim of this study was to test the possibility that metabolomics can be used to identify individuals with improved insulin sensitivity as a result of increased physical activity. Healthy and diabetic subjects were investigated before and after 3 months of exercise to determine various metabolic parameters. Insulin sensitivity was determined by hyperinsulinemic euglycemic clamps and found to be improved in the diabetic men. Plasma was collected during the clamp and analyzed through GC/TOFMS. Healthy subjects could be distinguished from diabetics by means of low molecular-weight compounds (LMC) in plasma independently of gender or exercise, and exercise induced differences in LMC patterns both for healthy and T2D subjects. Forty-four significant metabolites were found to explain differences between LMC patterns obtained from trained and non-trained diabetics. Among these compounds, 17 could be annotated and 5 classified. Inositol-1-phosphate showed the highest correlation to insulin sensitivity in diabetic men, whereas an as yet unknown fatty acid correlated best with insulin sensitivity in women. Both metabolites were better correlated to insulin sensitivity than glucose. Finally, the finding that inostitol-1-phosphate negatively correlates with insulin sensitivity in diabetic men, was validated using samples obtained from a similar training study on diabetic men.
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| 5. |
- Kuhl, Jeanette
(författare)
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Pathogenesis of type 2 diabetes with emphasis on the mechanism of insulin resistance
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Type 2 diabetes is characterized by chronic hyperglycemia and develops slowly through stages of early impairments of glucose metabolism. The disease is often associated with obesity, physical inactivity, decreased insulin sensitivity and impaired insulin responsiveness. An increase in the muscle concentration of malonyl CoA, an inhibitor of fatty-acid oxidation, has been observed in association with insulin resistance and type 2 diabetes. The thesis aimed to evaluate the influence of sex and diabetes heredity on the prevalence and pathogenesis of early abnormalities of glucose metabolism, as well as the impact of exercise training on phenotype characteristics and insulin sensitivity in people with or without mild type 2 diabetes. The impact of exercise training on cellular and molecular mechanisms regulating insulin sensitivity in muscle was also investigated. The subject-material comprised of approximately 8,000 men and women, with or without family history of type 2 diabetes (FHD). They participated in the Stockholm Diabetes Prevention Program (SDPP). The participants were categorized according to an oral glucose tolerance test (OGTT) and the homeostasis model assessment (HOMA) was used to determine insulin sensitivity and beta cell function. Thirteen men with type 2 diabetes and 17 sex, age-, and body mass index-matched control subjects were evaluated to compare phenotype characteristics, insulin sensitivity and malonyl CoA levels in biopsies from the vastus lateralis muscle. Furthermore, eleven healthy middle-aged controls and twelve patients with type 2 diabetes were investigated before and after a 12-week training program to explore molecular mechanisms mediating training improved insulin sensitivity. Prevalence of early abnormalities of glucose metabolism was two to three times higher in subjects with FHD and two to three times higher in men compared to women. In these subjects both waist circumference and systolic blood pressure were increased and insulin sensitivity and beta cell function were decreased. Subjects with impaired fasting glucose (IFG) had more pronounced impairment of beta cell function and insulin sensitivity than subjects with impaired glucose tolerance (IGT). Patients with type 2 diabetes had significantly lower physical fitness (V02max) and higher truncal fat mass compared to healthy controls. The plasma concentration of free fatty acids and the rate of fatty acid oxidation during the hyperinsulinemic euglycemic clamp, were higher in the diabetic subjects than in the controls. During the high-dose insulin clamp, the increase in cytosolic citrate and malate in muscle, which parallels and regulates malonyl CoA levels, was significantly less in patients. Despite this, a similar increase in the concentration of malonyl CoA was observed in the two groups, suggesting an abnormality in malonyl CoA regulation in the patients with type 2 diabetes. Long-term exercise training decreased intra-abdominal fat mass and improved V02max in both controls and patients. Subjects with type 2 diabetes improved insulin sensitivity by 77%, when measured by hyperinsulinemic euglycemic clamp, whereas no significant change was seen in the controls. Furthermore, after training the basal concentration of malonyl CoA in muscle was significantly decreased in both groups. This was accompanied by increased activity of malonyl CoA decarboxylase (MCD). In patients, the basal diacylglycerol (DAG) levels decreased after training whereas MCD mRNA and abundance of peroxisomal-proliferator-activated receptor (PPAR) γ co-activator 1 α (PGC-1α) increased in controls. No changes in the phosphorylation of AMP-activated protein kinase (AMPK) or acetyl CoA carboxylase (ACC) were seen. In conclusion, type 2 diabetes heredity and male sex increased the prevalence of early abnormalities of glucose homeostasis. Insulin sensitivity is decreased in mild type 2 diabetes which closely correlates with an increase in truncal fat mass, decrease in physical fitness and unexpectedly high levels of malonyl CoA in muscle. We propose that high levels of muscle malonyl CoA, in combination with decreased suppression of plasma FFA, constitute a crucial mechanism behind insulin resistance in type 2 diabetes. Physical training markedly improved insulin sensitivity and decreased intra-abdominal fat area in patients with type 2 diabetes. This study demonstrates for the first time in man that physical training increased activity of MCD in muscle. We believe that the latter mechanism significantly accounts for the decrease of muscle malonyl CoA and DAG, resulting in improved insulin sensitivity.
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| 6. |
- Mobarrez, Fariborz, et al.
(författare)
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The Effects of Smoking on Levels of Endothelial Progenitor Cells and Microparticles in the Blood of Healthy Volunteers
- 2014
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Ingår i: PLOS ONE. - San Francisco : Public Library of Science. - 1932-6203. ; 9:2, s. e90314-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cigarette smoking, both active and passive, is one of the leading causes of morbidity and mortality in cardiovascular disease. To assess the impact of brief smoking on the vasculature, we determined levels of circulating endothelial progenitor cells (EPCs) and circulating microparticles (MPs) following the smoking of one cigarette by young, healthy intermittent smokers. Materials and Methods: 12 healthy volunteers were randomized to either smoking or not smoking in a crossover fashion. Blood sampling was performed at baseline, 1, 4 and 24 hours following smoking/not smoking. The numbers of EPCs and MPs were determined by flow cytometry. MPs were measured from platelets, leukocytes and endothelial cells. Moreover, MPs were also labelled with anti-HMGB1 and SYTO 13 to assess the content of nuclear molecules. Results: Active smoking of one cigarette caused an immediate and significant increase in the numbers of circulating EPCs and MPs of platelet-, endothelial-and leukocyte origin. Levels of MPs containing nuclear molecules were increased, of which the majority were positive for CD41 and CD45 (platelet-and leukocyte origin). CD144 (VE-cadherin) or HMGB1 release did not significantly change during active smoking. Conclusion: Brief active smoking of one cigarette generated an acute release of EPC and MPs, of which the latter contained nuclear matter. Together, these results demonstrate acute effects of cigarette smoke on endothelial, platelet and leukocyte function as well as injury to the vascular wall.
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| 7. |
- Nyström, Thomas, et al.
(författare)
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Estimated glucose disposal rate and long-term survival in type 2 diabetes after coronary artery bypass grafting.
- 2017
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Ingår i: Heart and vessels. - : Springer Science and Business Media LLC. - 1615-2573 .- 0910-8327. ; 32:3, s. 269-278
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Tidskriftsartikel (refereegranskat)abstract
- We performed a nationwide population-based cohort study to investigate the association between estimated glucose disposal rate (eGDR) and long-term survival after coronary artery bypass grafting (CABG) in patients with type 2 diabetes. All patients who underwent primary CABG in Sweden from 2006 to 2013 were identified from the SWEDEHEART register and by record linkage to the National Diabetes Register; all patients with type 2 diabetes were included and formed the study population. Patients were followed until 2013 through national registers for major adverse cardiovascular events and death from any cause. eGDR was calculated using waist circumference, hemoglobin A1c, and presence or the absence of hypertension. The association between eGDR and death was estimated using multivariable Cox regression. A total of 3256 patients were included. During a mean follow-up of 3.1years (10,227 person-years), in total, 14% patients died: 17% (n=186) in the 1st tertile (lowest eGDR), 14% (n=145) in the 2nd tertile, and 13% (n=133) in the 3rd tertile (highest eGDR). There was a significant association between eGDR and increased risk of death: adjusted hazard ratio (95% confidence interval): 1.46 (1.12-1.90) for the 1st eGDR tertile compared to the 3rd and highest eGDR tertile. In conclusion, patients with type 2 diabetes who underwent CABG, a low eGDR, were associated with an increased risk of long-term all-cause mortality that was independent of other cardiovascular and metabolic risk factors. Insulin resistance measured by eGDR could be a useful risk marker in patients with type 2 diabetes and ischemic heart disease.
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