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- Venskutonyte, L, et al.
(author)
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Satisfaction with glucose-lowering treatment and well-being in patients with type 2 diabetes and myocardial infarction: a DIGAMI2 QoL sub-study
- 2013
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In: Diabetes & vascular disease research. - : SAGE Publications. - 1752-8984 .- 1479-1641. ; 10:3, s. 263-269
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Journal article (peer-reviewed)abstract
- The second Diabetes Glucose and Myocardial Infarction (DIGAMI 2) study randomised patients with diabetes and myocardial infarction to insulin or oral-based treatment. To determine the effects of insulin-based treatment, the Diabetes Treatment Satisfaction Questionnaire (DTSQ) and the Psychological General Well-Being (PGWB) Index were administered at baseline and 12 months. Insulin-treated patients ( n = 197) had a worse risk profile and more co-morbidity at baseline than patients on oral glucose-lowering agents ( n = 127). The treatment satisfaction and psychological well-being was similar between insulin and oral groups at baseline [DTSQ: median (first–third quartile) 30 (24–34) vs 31 (27–34), NS; PGWB: 77 (73–82) vs 79 (76–82), NS] and at 12 months [DTSQ: 32 (28–35) vs 34 (30–36), NS; PGWB: 81 (78–84) vs 82 (78–84), NS]. Improvement was significant in both groups. Insulin-based therapy was well accepted and did not decrease treatment satisfaction or psychological well-being compared to oral glucose-lowering treatment in patients with type 2 diabetes and myocardial infarction.
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- Chew, Michelle, et al.
(author)
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Extravascular lung water index: Diagnostic accuracy and relation to lung injury and mortality in patients with shock
- 2011
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In: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 37:1 Suppl, s. 98-98
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Conference paper (peer-reviewed)abstract
- INTRODUCTION. The diagnosis of acute lung injury may be more robust if more accurate physiological markers can be identified. Extravascular lung water index (EVLWI) may be useful and has been shown to correlate with respiratory function and mortality in patients with sepsis and ARDS. Whether this applies to a wider population, and which index performs best, are unclear. OBJECTIVES. We hypothesized that EVLWI correlates with respiratory function and mortality in patients with documented systemic inflammation and shock. We investigated EVLW indexed to actual and predicted body weight, and pulmonary blood volume. We investigated the diagnostic accuracy of EVLWI for lung injury. METHODS. In 51 patients with shock and SIRS, EVLWI was measured within 6 h of ICU admission and indexed to actual weight (EVLWI/ABW), predicted body weight (EVLWI/ PBW) and pulmonary blood volume (EVLWI/PBV). Relationships to lung injury and ICUmortality were investigated. Positive and negative likelihood ratios, pre- and post-test odds and ROC curves were calculated. RESULTS. EVLWI was higher among patients with lung injury and was significantly correlated with respiratory parameters. EVLWI/ABW was higher among non-survivors and gave the best positive likelihood ratios for diagnosing ALI/ARDS. In contrast, EVLWI/PBV gave better diagnostic value for severe lung injury according to Murray's LIS criteria. The post-test odds for ALI and ARDS increased threefold when using EVLWI/ABW as a bedside test. The post-test odds of severe lung injury increased eightfold using EVLWI/PBV. EVLWI/ABW and EVLWI/PBV generated the best ROC curves for mortality prediction with a sensitivity of 68% and specificity of 63-72%. CONCLUSIONS. EVLWI was associated with degree of lung injury, regardless of the index used, supporting its usefulness as a bedside indicator for disease severity. EVLWI/PBV and EVLW/ABW gave the best diagnostic accuracies for the diagnosis of lung injury, and generated the bestROCcurves for mortality prediction.EVLWI/ABWwas significantly increased in non-survivors. Further studies are needed to confirm the additional value of EVLWI for the early identification of lung injury.
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- Hage, C, et al.
(author)
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The DPP-4 inhibitor sitagliptin and endothelial function in patients with acute coronary syndromes and newly detected glucose perturbations: A report from the BEGAMI study
- 2014
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In: Diabetes & vascular disease research. - : SAGE Publications. - 1752-8984 .- 1479-1641. ; 11:4, s. 290-293
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Journal article (peer-reviewed)abstract
- Compromised endothelial function contributes to poor prognosis in patients with coronary artery disease and type 2 diabetes. Incretin-based therapy may exert beneficial cardiovascular effects beyond glucose lowering. We tested whether sitagliptin improves endothelial function. Research design and methods: In the double-blind BEta-cell function in patients with Glucose Abnormalities and Acute Myocardial Infarction (BEGAMI) trial, acute coronary syndrome (ACS)-patients with newly detected impaired glucose tolerance (IGT) or type 2 diabetes mellitus (T2DM) were randomised to sitagliptin 100 mg (n = 31) or placebo (n = 33) during 12 weeks. Endothelial function was studied as reactive hyperaemia index (RHI). Results: At baseline, the RHI was slightly compromised in both groups (sitagliptin 1.67; Q1;Q3: 1.46;2.17 vs placebo 1.61; 1.44;1.96; ns). The RHI did not change during the study period and was 1.57 (1.40;2.36) in the sitagliptin and 1.60 (1.46;1.81; ns) in the placebo group after treatment. Conclusion: Sitagliptin did not improve endothelial function in patients with ACS and newly detected glucose perturbations.
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| 14. |
- Katz, P, et al.
(author)
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The clinical burden of type 2 diabetes in patients with acute coronary syndromes: prognosis and implications for short- and long-term management
- 2014
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In: Diabetes & vascular disease research. - : SAGE Publications. - 1752-8984 .- 1479-1641. ; 11:6, s. 395-409
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Journal article (peer-reviewed)abstract
- Type 2 diabetes mellitus (T2DM) is associated with increased morbidity and mortality in patients with acute coronary syndromes (ACS). Cardiometabolic risk factors, including hyperglycaemia, insulin resistance, atherogenic dyslipidaemia, increased visceral fat and inflammation, are associated with increased risk in this population and represent potential targets for treatment. In this review, management strategies for patients with T2DM post-ACS, both in the acute-care setting and in the long-term, are discussed. Although the benefits of long-term, aggressive, multifactorial risk factor modification are well established, a significant burden of recurrent events remains and the search for novel strategies continues. Several studies are assessing the potential cardiovascular (CV) benefits and safety of various classes of newer agents. Of these, AleCardio (aleglitazar), Examination of Cardiovascular Outcomes With Alogliptin versus Standard of Care in Patients With Type 2 Diabetes Mellitus and Acute Coronary Syndrome (EXAMINE; alogliptin) and Evaluation of LIXisenatide in Acute Coronary Syndrome (ELIXA; lixisenatide) specifically address patients with type 2 diabetes post-ACS. The mechanisms of action of these new therapies and aims of the CV outcome studies are briefly reviewed. The prevalence of type 2 diabetes continues to increase worldwide highlighting the need for new strategies that address the complex underlying processes that drive atherosclerosis and CV events in this high-risk patient population.
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- Mellbin, L. G., et al.
(author)
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The relationship between glycaemic variability and cardiovascular complications in patients with acute myocardial infarction and type 2 diabetes: a report from the DIGAMI 2 trial
- 2013
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In: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 34:5, s. 374-379
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Journal article (peer-reviewed)abstract
- AimsHyperglycaemia during hospitalization for acute myocardial infarction (AMI) is a risk predictor, but attempts to improve the prognosis by insulin-based glucose control have not been consistently successful. Increased glycaemic variability, a potential effect of insulin treatment, has been linked to a worse prognosis in critically ill patients. The present aim was to study the possibility of such a relation in patients with type 2 diabetes (T2DM) and AMI.Method and resultsWe studied 578 T2DM patients who had glucose levels measured hourly while receiving an insulin-glucose infusion during the first 48 h of hospitalization for AMI. Three measures of glycaemic variability: root mean square error (RMSE), range, and slope were studied in relation to a composite endpoint of mortality, stroke, and reinfarction and to mortality.In unadjusted analyses, the mean level of glycaemic variability did not differ between patients who died during 12 months of follow-up compared with those who survived. In a Cox regression model adjusting for age and previous congestive heart failure, there was no increased risk for the composite endpoint associated with increased glycaemic variability; RMSE: hazard ratio (HR) 1.09 [95% confidence interval (CI) 0.93-1.27; P = 0.28], range: HR 1.01 (95% CI: 0.98-1.05; P = 0.47), and slope: HR 1.01 (95% CI: 0.99-1.04; P = 0.40). There was furthermore no increased risk in mortality; RMSE HR 1.14 (95% CI: 0.93-1.38; P = 0.21), range HR 1.03 (95% CI: 0.98-1.08; P = 0.28), and slope HR 1.01 (95% CI: 0.98-1.04; P = 0.55).ConclusionThe 1-year risk for death, reinfarction, or stroke did not relate to glycaemic variability in T2DM patients with AMI treated with insulin infusion.
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| 26. |
- Ryden, L, et al.
(author)
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Glucose perturbations and cardiovascular risk: challenges and opportunities
- 2012
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In: Diabetes & vascular disease research. - : SAGE Publications. - 1752-8984 .- 1479-1641. ; 9:3, s. 170-176
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Journal article (peer-reviewed)abstract
- People with disturbed glucose metabolism are at an increased risk for cardiovascular disease. This risk starts before diabetes, according to present definitions, is established. Early detection of impaired glucose tolerance and target-driven multifactorial management incorporating all risk factors in a broad sense may effectively improve the prognosis for these persons. Management includes early detection of glucose perturbations and preventing or delaying future diabetes among people with impaired glucose tolerance. In people with established diabetes, hypertension, hyperlipidaemia and hyperglycaemia are all important factors to monitor and, if these are above the recommended levels, to treat, first hand with lifestyle-oriented recommendations, although usually supported by pharmacological interventions. Since impaired glucose tolerance and type 2 diabetes mellitus are rapidly increasing in the population, glucose perturbations as the cause of cardiovascular disease manifestations will become more common. Development of macrovascular complications substantially impacts care costs, and proper management of these individuals will therefore not only decrease personal suffering but also clearly impact health care expenditures.
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| 34. |
- Venskutonyte, L, et al.
(author)
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Self-rated health predicts outcome in patients with type 2 diabetes and myocardial infarction: a DIGAMI 2 quality of life sub-study
- 2013
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In: Diabetes & vascular disease research. - : SAGE Publications. - 1752-8984 .- 1479-1641. ; 10:4, s. 361-367
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Journal article (peer-reviewed)abstract
- The Diabetes mellitus Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) 2 Quality of Life (QoL) sub-study included 465 patients with type 2 diabetes and acute myocardial infarction (AMI) followed for 2 years. Self-rated health was reported by the rating scale (RS), graded 0 = death to 100 = perfect health. Prospective associations between RS and all-cause mortality, cardiovascular (CV) death and cardiovascular events (CVEs = CV death, non-fatal AMI, stroke) were assessed. Median age was 68 years (range 59–74), 68% male. Patients experiencing CVE ( n = 132) or death ( n = 71) had lower RS compared with patients free from events: 60 (50–79) versus 70 (55–81) ( p < 0.001) and 60 (50–75) versus 70 (51–80) ( p = 0.008). The RS score predicted CVE [hazard ratio (HR); 95% confidence interval (CI): 0.87; 0.80–0.95] and all-cause mortality (0.86; 0.76–0.97), and corresponding HRs after adjustment were 0.90; 0.83–0.99 and 0.90; 0.79–1.02, respectively. A low self-rated health is of prognostic importance in patients with type 2 diabetes and AMI and may serve as an easily obtainable indicator of high risk for CVEs supplementing traditional risk factors.
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| 38. |
- Arner, Erik, et al.
(author)
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Adipocyte Turnover : Relevance to Human Adipose Tissue Morphology
- 2010
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In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 59:1, s. 105-109
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Journal article (peer-reviewed)abstract
- OBJECTIVE-Adipose tissue may contain few large adipocytes (hypertrophy) or many small adipocytes (hyperplasia). We investigated factors of putative importance for adipose tissue morphology. RESEARCH DESIGN AND METHODS-Subcutaneous adipocyte size and total fat mass were compared in 764 subjects with BMI 18-60 kg/m(2). A morphology value was defined as tire difference between the measured adipocyte volume and the expected volume given by a curved-line fit for a given body fat mass and was related to insulin values. In 35 subjects, in vivo adipocyte turnover was measured by exploiting incorporation of atmospheric C-14 into DNA. RESULTS-Occurrence of hyperplasia (negative morphology value) or hypertrophy (positive morphology value) was independent of sex and body weight but con-elated with fasting plasma insulin levels and insulin sensitivity, independent of adipocyte volume (beta-coefficient = 0.3, P < 0.0001). Total adipocyte number and morphology were negatively related (r = -0.66); i.e., the total adipocyte number was greatest in pronounced hyperplasia and smallest in pronounced hypertrophy. The absolute number of new adipocytes generated each year was 70% lower (P < 0.001) in hypertrophy than in hyperplasia, and individual values for adipocyte generation and morphology were strongly related (r = 0.7, P < 0.001). The relative death rate (similar to 10% per year) or mean age of adipocytes (similar to 10 years) was not correlated with morphology. CONCLUSIONS-Adipose tissue morphology correlates with insulin measures and is linked to the total adipocyte number independently of sex and body fat level. Low generation rates of adipocytes associate with adipose tissue hypertrophy, whereas high generation rates associate with adipose hyperplasia. Diabetes 59:105-109, 2010
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| 39. |
- Arner, Peter, et al.
(author)
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Dynamics of human adipose lipid turnover in health and metabolic disease
- 2011
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 478:7367, s. 110-113
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Journal article (peer-reviewed)abstract
- Adipose tissue mass is determined by the storage and removal of triglycerides in adipocytes(1). Little is known, however, about adipose lipid turnover in humans in health and pathology. To study this in vivo, here we determined lipid age by measuring (14)C derived from above ground nuclear bomb tests in adipocyte lipids. We report that during the average ten-year lifespan of human adipocytes, triglycerides are renewed six times. Lipid age is independent of adipocyte size, is very stable across a wide range of adult ages and does not differ between genders. Adipocyte lipid turnover, however, is strongly related to conditions with disturbed lipid metabolism. In obesity, triglyceride removal rate (lipolysis followed by oxidation) is decreased and the amount of triglycerides stored each year is increased. In contrast, both lipid removal and storage rates are decreased in non-obese patients diagnosed with the most common hereditary form of dyslipidaemia, familial combined hyperlipidaemia. Lipid removal rate is positively correlated with the capacity of adipocytes to break down triglycerides, as assessed through lipolysis, and is inversely related to insulin resistance. Our data support a mechanism in which adipocyte lipid storage and removal have different roles in health and pathology. High storage but low triglyceride removal promotes fat tissue accumulation and obesity. Reduction of both triglyceride storage and removal decreases lipid shunting through adipose tissue and thus promotes dyslipidaemia. We identify adipocyte lipid turnover as a novel target for prevention and treatment of metabolic disease.
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| 43. |
- De Pascalis, Roberto, et al.
(author)
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Models Derived from In Vitro Analyses of Spleen, Liver, and Lung Leukocyte Functions Predict Vaccine Efficacy against the Francisella tularensis Live Vaccine Strain (LVS)
- 2014
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In: mBio. - 2161-2129 .- 2150-7511. ; 5:2
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Journal article (peer-reviewed)abstract
- Currently, there are no licensed vaccines and no correlates of protection against Francisella tularensis, which causes tularemia. We recently demonstrated that measuring in vitro control of intramacrophage bacterial growth by murine F. tularensis-immune splenocytes, as well as transcriptional analyses, discriminated Francisella vaccines of different efficacies. Further, we identified potential correlates of protection against systemic challenge. Here, we extended this approach by studying leukocytes derived from lungs and livers of mice immunized by parenteral and respiratory routes with F. tularensis vaccines. Liver and lung leukocytes derived from intradermally and intranasally vaccinated mice controlled in vitro Francisella Live Vaccine Strain (LVS) intramacrophage replication in patterns similar to those of splenocytes. Gene expression analyses of potential correlates also revealed similar patterns in liver cells and splenocytes. In some cases (e. g., tumor necrosis factor alpha [TNF-alpha], interleukin 22 [IL-22], and granulocyte-macrophage colony-stimulating factor [GM-CSF]), liver cells exhibited even higher relative gene expression, whereas fewer genes exhibited differential expression in lung cells. In contrast with their strong ability to control LVS replication, splenocytes from intranasally vaccinated mice expressed few genes with a hierarchy of expression similar to that of splenocytes from intradermally vaccinated mice. Thus, the relative levels of gene expression vary between cell types from different organs and by vaccination route. Most importantly, because studies comparing cell sources and routes of vaccination supported the predictive validity of this coculture and gene quantification approach, we combined in vitro LVS replication with gene expression data to develop analytical models that discriminated between vaccine groups and successfully predicted the degree of vaccine efficacy. Thus, this strategy remains a promising means of identifying and quantifying correlative T cell responses.IMPORTANCEIdentifying and quantifying correlates of protection is especially challenging for intracellular bacteria, including Francisella tularensis. F. tularensis is classified as a category A bioterrorism agent, and no vaccines have been licensed in the United States, but tularemia is a rare disease. Therefore, clinical trials to test promising vaccines are impractical. In this report, we further evaluated a novel approach to developing correlates by assessing T cell immune responses in lungs and livers of differentially vaccinated mice; these nonprofessional immune tissues are colonized by Francisella. The relative degree of vaccine efficacy against systemic challenge was reflected by the ability of immune T cells, particularly liver T cells, to control the intramacrophage replication of bacteria in vitro and by relative gene expression of several immunological mediators. We therefore developed analytical models that combined bacterial replication data and gene expression data. Several resulting models provided excellent discrimination between vaccines of different efficacies.
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| 44. |
- Ersson, B, et al.
(author)
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Introduction to protein purification
- 2011. - 3
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In: Protein Purification, Principles, High Resolution Methods and Applications. - : John Wiley & Sons Inc.. - 9780471746614 ; , s. 3-22
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Book chapter (other academic/artistic)
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| 45. |
- Ferrandis, Maria-José, et al.
(author)
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Ruling out cardiac failure : Cost-benefit analysis of a sequential testing strategy with NT-proBNP before echocardiography
- 2013
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In: Upsala Journal of Medical Sciences. - : Informa Healthcare. - 0300-9734 .- 2000-1967. ; 118:2, s. 75-79
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Journal article (peer-reviewed)abstract
- Objectives. To estimate the possible economic benefit of a sequential testing strategy with NT-proBNP to reduce the number of echocardiographies.Methods. Retrospective study in a third-party payer perspective. The costs were calculated from three Swedish counties: Blekinge, Östergötland, and Uppland. Two cut-off levels of NT-proBNP were used: 400 and 300 pg/mL. The cost-effectiveness of the testing strategy was estimated through the short-term cost avoidance and reduction in demand for echocardiographies.Results. The estimated costs for NT-proBNP tests and echocardiographies per county were reduced by 33%–36% with the 400 pg/mL cut-off and by 28%–29% with the 300 pg/mL cut-off. This corresponded to a yearly cost reduction of approximately €2–5 million per million inhabitants in these counties.Conclusion. The use of NT-proBNP as a screening test could substantially reduce the number of echocardiographies in the diagnostic work-up of patients with suspected cardiac failure, as well as the associated costs.
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| 46. |
- Griffin, Robert M., et al.
(author)
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The Shared Genome Is a Pervasive Constraint on the Evolution of Sex-Biased Gene Expression
- 2013
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In: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 30:9, s. 2168-2176
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Journal article (peer-reviewed)abstract
- Males and females share most of their genomes, and differences between the sexes can therefore not evolve through sequence divergence in protein coding genes. Sexual dimorphism is instead restricted to occur through sex-specific expression and splicing of gene products. Evolution of sexual dimorphism through these mechanisms should, however, also be constrained when the sexes share the genetic architecture for regulation of gene expression. Despite these obstacles, sexual dimorphism is prevalent in the animal kingdom and commonly evolves rapidly. Here, we ask whether the genetic architecture of gene expression is plastic and easily molded by sex-specific selection, or if sexual dimorphism evolves rapidly despite pervasive genetic constraint. To address this question, we explore the relationship between the intersexual genetic correlation for gene expression (r(MF)), which captures how independently genes are regulated in the sexes, and the evolution of sex-biased gene expression. Using transcriptome data from Drosophila melanogaster, we find that most genes have a high r(MF) and that genes currently exposed to sexually antagonistic selection have a higher average r(MF) than other genes. We further show that genes with a high r(MF) have less pronounced sex-biased gene expression than genes with a low r(MF) within D. melanogaster and that the strength of the r(MF) in D. melanogaster predicts the degree to which the sex bias of a gene's expression has changed between D. melanogaster and six other species in the Drosophila genus. In sum, our results show that a shared genome constrains both short- and long-term evolution of sexual dimorphism.
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| 47. |
- Gyberg, V, et al.
(author)
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Policymakers' perceptions of cardiovascular health in Europe
- 2011
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In: European journal of cardiovascular prevention and rehabilitation : official journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology. - : Oxford University Press (OUP). - 1741-8275. ; 18:5, s. 745-753
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Journal article (peer-reviewed)
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