| 1. |
- Axelsson, Annika, et al.
(författare)
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Sox5 regulates beta-cell phenotype and is reduced in type 2 diabetes
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Type 2 diabetes (T2D) is characterized by insulin resistance and impaired insulin secretion, but the mechanisms underlying insulin secretion failure are not completely understood. Here, we show that a set of co-expressed genes, which is enriched for genes with islet-selective open chromatin, is associated with T2D. These genes are perturbed in T2D and have a similar expression pattern to that of dedifferentiated islets. We identify Sox5 as a regulator of the module. Sox5 knockdown induces gene expression changes similar to those observed in T2D and diabetic animals and has profound effects on insulin secretion, including reduced depolarization-evoked Ca 2+-influx and β-cell exocytosis. SOX5 overexpression reverses the expression perturbations observed in a mouse model of T2D, increases the expression of key β-cell genes and improves glucose-stimulated insulin secretion in human islets from donors with T2D. We suggest that human islets in T2D display changes reminiscent of dedifferentiation and highlight SOX5 as a regulator of β-cell phenotype and function.
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| 2. |
- Bager, Johan-Emil, et al.
(författare)
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Long-term risk-factor control and secondary prevention are insufficient after first TIA: Results from QregPV.
- 2023
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Ingår i: European stroke journal. - 2396-9873 .- 2396-9881. ; 9:1, s. 154-161
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Tidskriftsartikel (refereegranskat)abstract
- Long-term risk-factor control and secondary prevention are not well characterized in patients with a first transient ischemic attack (TIA). With baseline levels as reference, we compared primary-care data on blood pressure (BP), low-density lipoprotein cholesterol (LDL-C), smoking, and use of antihypertensives, statins and antiplatelet treatment/oral anticoagulation (APT/OAC) during 5years after a first TIA.Patients in QregPV, a Swedish primary-care register for the Region of Västra Götaland, with a first TIA discharge diagnosis from wards proficient in stroke care 2010 to 2012 were identified and followed up to 5years. BP, LDL-C, smoking, use of antihypertensives, statins, APT/OAC, and achievement of target levels were calculated. We used logistic mixed-effect models to analyze the effect of follow-up over time on risk-factor control and secondary prevention treatment.We identified 942 patients without prior cerebrovascular disease who had a first TIA. Compared to baseline, the first year of follow-up was associated with improvements in concomitant attainment of BP <140/90mmHg, LDL-C<2.6mmol/L and non-smoking, which rose from 20% to 33% (OR 2.08, 95% CI 1.38-3.13), but then stagnated in years 2-5. In the first year of follow-up, 47% of patients had complete secondary prevention treatment (antihypertensives, APT/OAC and statin), but continued follow-up was associated with a yearly decrease in secondary prevention treatment (OR 0.94, 95% CI 0.94-0.98).Risk-factor control was inadequate, leaving considerable potential for improved secondary prevention treatment after a first TIA in Swedish patients followed up to 5years.
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| 3. |
- Bardel, Annika, 1952-, et al.
(författare)
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Age and sex related self-reported symptoms in a general population across 30 years: Patterns of reporting and secular trend
- 2019
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 14:2
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Tidskriftsartikel (refereegranskat)abstract
- Objective :To study age and sex specific prevalence of 30 symptoms in random samples from the general population and to analyze possible secular trends across time. Study population: The study was based on data from eight on-going Swedish cohort studies, with baseline investigations performed between 1973 and 2003. Samples were drawn from the general population of the cities of Gothenburg and Eskilstuna, and of Uppsala County. Overall, 20,160 subjects were sampled, 14,470 (71.8%) responded, of whom 12.000 were unique subjects, and 2548 were part of more than one sample. Methods: The Complaint score sub-scale of the Gothenburg Quality of Life instrument, listing 30 general symptoms was used. Responders were asked to indicate which symptoms they had experienced during the last three months. Results: Women reported on average 7.8 symptoms, and men 5.3 (p<0.0001). Women reported higher prevalence than men for 24 of the 30 symptoms. In multivariate analyses four patterns of prevalence across age were identified in both men and women; increasing prevalence, decreasing, stable and biphasic prevalence. The symptoms in the various pattern groups differed somewhat between men and women. However, symptoms related to strain were prominent among symptoms decreasing with age. Moreover, there were secular trends. Across all symptoms reporting prevalence increased over time in men (p<0.001) as well as in women (p<0.0001). Conclusions: Women reported higher total symptom prevalence than men. Symptoms related to health generally increased with age, while symptoms related to stress decreased markedly. Significant secular trends across time regarding symptom prevalence were found. © 2019 Bardel et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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| 4. |
- Danesh, John, et al.
(författare)
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Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis
- 2005
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Ingår i: JAMA: The Journal of the American Medical Association. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 294:14, s. 1799-1809
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Forskningsöversikt (refereegranskat)abstract
- CONTEXT: Plasma fibrinogen levels may be associated with the risk of coronary heart disease (CHD) and stroke. OBJECTIVE: To assess the relationships of fibrinogen levels with risk of major vascular and with risk of nonvascular outcomes based on individual participant data. DATA SOURCES: Relevant studies were identified by computer-assisted searches, hand searches of reference lists, and personal communication with relevant investigators. STUDY SELECTION: All identified prospective studies were included with information available on baseline fibrinogen levels and details of subsequent major vascular morbidity and/or cause-specific mortality during at least 1 year of follow-up. Studies were excluded if they recruited participants on the basis of having had a previous history of cardiovascular disease; participants with known preexisting CHD or stroke were excluded. DATA EXTRACTION: Individual records were provided on each of 154,211 participants in 31 prospective studies. During 1.38 million person-years of follow-up, there were 6944 first nonfatal myocardial infarctions or stroke events and 13,210 deaths. Cause-specific mortality was generally available. Analyses involved proportional hazards modeling with adjustment for confounding by known cardiovascular risk factors and for regression dilution bias. DATA SYNTHESIS: Within each age group considered (40-59, 60-69, and > or =70 years), there was an approximately log-linear association with usual fibrinogen level for the risk of any CHD, any stroke, other vascular (eg, non-CHD, nonstroke) mortality, and nonvascular mortality. There was no evidence of a threshold within the range of usual fibrinogen level studied at any age. The age- and sex- adjusted hazard ratio per 1-g/L increase in usual fibrinogen level for CHD was 2.42 (95% confidence interval [CI], 2.24-2.60); stroke, 2.06 (95% CI, 1.83-2.33); other vascular mortality, 2.76 (95% CI, 2.28-3.35); and nonvascular mortality, 2.03 (95% CI, 1.90-2.18). The hazard ratios for CHD and stroke were reduced to about 1.8 after further adjustment for measured values of several established vascular risk factors. In a subset of 7011 participants with available C-reactive protein values, the findings for CHD were essentially unchanged following additional adjustment for C-reactive protein. The associations of fibrinogen level with CHD or stroke did not differ substantially according to sex, smoking, blood pressure, blood lipid levels, or several features of study design. CONCLUSIONS: In this large individual participant meta-analysis, moderately strong associations were found between usual plasma fibrinogen level and the risks of CHD, stroke, other vascular mortality, and nonvascular mortality in a wide range of circumstances in healthy middle-aged adults. Assessment of any causal relevance of elevated fibrinogen levels to disease requires additional research.
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| 5. |
- Dotevall, Annika, 1957, et al.
(författare)
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Considerable disturbances of cardiovascular risk factors in women with diabetes and myocardial infarction
- 2005
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Ingår i: J Diabetes Complications. - : Elsevier BV. - 1056-8727. ; 19:1, s. 26-34
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate to which extent differences in cardiovascular risk factors explain the increased risk of myocardial infarction (MI) and complication rate in women with diabetes mellitus (DM). DESIGN: Case-control study. SUBJECTS: We compared women with diabetes and previous MI (n=29), diabetes but no MI (n=46), prior MI but no diabetes (n=64), and healthy controls (n=125). MEASUREMENTS: Smoking habits, physical activity, blood pressure (BP), body mass index (BMI), waist/hip ratio (WHR), serum lipids, plasma fibrinogen, and serum sex hormones. RESULTS: Despite the fact that diabetic women had similar BMI, those with a past MI, compared to diabetic women without MI, had significantly higher WHR (mean, 95% CI) [0.89 (0.87, 0.92) vs. 0.84 (0.81, 0.86) mmol/l, P=.001] and very high S-triglycerides [3.03 (2.23, 3.83) vs. 1.69, (1.39, 1.99) mmol/l, P=.001] and low HDL-cholesterol [1.09 (0.94, 1.24) vs. 1.56 (1.41, 1.71) mmol/l, P<.001], indicating pronounced metabolic disturbances. Women with MI but no diabetes had intermediate values for WHR, triglycerides, and HDL-cholesterol. Furthermore, women with diabetes and MI had significantly higher p-fibrinogen, were smokers, and lived a more sedentary life than the other women. Over half of all women with prior MI were on lipid-lowering therapy and tended to have nonsignificantly lower S-cholesterol than women without MI. CONCLUSIONS: Women with diabetes who have manifested an MI carry a very substantial cardiovascular risk factor burden, which probably explain their increased morbidity and mortality. In order to improve prognosis, studies targeted at investigating treatment modalities for these abnormalities are needed.
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| 6. |
- Dotevall, Annika, 1957, et al.
(författare)
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Diabetes mellitus: clinical presentation and outcome in men and women with acute coronary syndromes. Data from the Euro Heart Survey ACS
- 2005
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Ingår i: Diabet Med. - 0742-3071 .- 1464-5491. ; 22:11, s. 1542-50
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To study clinical presentation, in-hospital course and short-term prognosis in men and women with diabetes mellitus and acute coronary syndromes (ACS). METHODS: Men (n = 6488, 21.2% with diabetes) and 2809 women (28.7% with diabetes) < or = 80 years old, with a discharge diagnosis of ACS were prospectively enrolled in the Euro Heart Survey of ACS. RESULTS: Women with diabetes were more likely to present with ST elevation than non-diabetic women, a difference that became more marked after adjustment for differences in smoking, hypertension, obesity, medication and prior disease [adjusted odds ratio (OR) 1.46 (1.20, 1.78)], whereas there was little difference between diabetic and non-diabetic men [adjusted OR 0.99 (0.86, 1.14)]. In addition, women with diabetes were more likely to develop Q-wave myocardial infarction (MI) than non-diabetic women [adjusted OR 1.61 (1.30, 1.99)], while there was no difference between men with and without diabetes [adjusted OR 0.99 (0.85, 1.15)]. There were significant interactions between sex, diabetes and presenting with ST-elevation ACS (P < 0.001), and Q-wave MI (P < 0.001), respectively. Of the women with diabetes, 7.4% died in hospital, compared with 3.6% of non-diabetic women [adjusted OR 2.13 (1.39, 3.26)], whereas corresponding mortality rates in men with and without diabetes were 4.1% and 3.3%, respectively [OR 1.13 (0.76, 1.67)] (P for diabetes-sex interaction 0.021). CONCLUSION: In women with ACS, diabetes is associated with higher risk of presenting with ST-elevation ACS, developing Q-wave MI, and of in-hospital mortality, whereas in men with ACS diabetes is not significantly associated with increased risk of either. These findings suggest a differential effect of diabetes on the pathophysiology of ACS based on the patient's sex.
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| 7. |
- Dotevall, Annika, 1957, et al.
(författare)
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Increased levels of triglycerides, BMI and blood pressure and low physical activity increase the risk of diabetes in Swedish women. A prospective 18-year follow-up of the BEDA study
- 2004
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Ingår i: Diabet Med. - 0742-3071. ; 21:6, s. 615-22
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To investigate risk factors for the development of diabetes in middle-aged women. METHODS: A random population sample of 1351 women without prior diabetes or cardiovascular disease, aged 39-65 years, took part in a screening study in 1979-1981 with questionnaires, physical examination and blood sampling. Development of diabetes up to 1998 was identified at a second examination in 1997-1998. RESULTS: Seventy-three women (5.4%) were diagnosed with diabetes during follow-up. As expected, obesity resulted in a rising age-adjusted risk with hazards ratio 3.2 [95% confidence interval (CI) 1.3, 8.1] at body mass index (BMI) 24-27 kg/m(2), and 8.3 (3.5, 19.7), at BMI > or = 27, compared with BMI < 22 kg/m(2). S-triglycerides (TG) carried a steeply increasing age-adjusted risk with hazards ratio 4.0 (95% CI 2.1, 7.6) already at s-TG 1.0-1.4 mmol/l, 7.1 (3.6, 14.0) at s-TG 1.5-1.9 mmol/l and 9.3 (4.3, 20.2) at s-TG > or = 2.0 mmol/l compared with s-TG < 1.0 mmol/l. Increasing systolic blood pressure (SBP) to 130-144, 145-159 and > or = 160 mmHg escalated the hazards ratio of diabetes to 1.6 (0.8, 3.3), 3.6 (1.7, 7.4) and 5.6 (2.7, 11.4), respectively, compared with SBP < 130 mmHg. Also, low physical activity predicted diabetes, with hazards ratio 2.1 (1.3, 3.3) for sedentary compared with non-sedentary activity. Smoking was not associated with increased risk of diabetes. After adjustment for BMI, SBP and physical activity, increasing TG level remained a strong and significant risk factor for diabetes [hazards ratio 3.0 (1.6, 5.7), 3.7 (1.8, 7.7) and 4.5 (2.0, 10.0), P < 0.001]. CONCLUSIONS: Among middle-aged Swedish women even very slightly elevated s-TG resulted in a considerably enhanced risk of developing diabetes, which was independent of age, BMI, blood pressure and physical activity.
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| 8. |
- Dotevall, Annika, 1957, et al.
(författare)
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Sex-related aspects on abnormal glucose regulation in patients with coronary artery disease
- 2007
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 28:3, s. 310-315
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Tidskriftsartikel (refereegranskat)abstract
- Aim To investigate the prevalence of diabetes and impaired glucose regulation (IGR) in a large cohort of men and women with coronary artery disease (CAD), and to describe the effect of abnormal glucose regulation by sex on symptoms, clinical course, and diagnosis. Methods and results A total of 4855 patients with CAD (median age 66 years; 29% women) were analysed within the framework of the Euro Heart Survey on Diabetes and the Heart. In all, 967 (28.1%) men and 528 (37.5%) women had diabetes. Of 3185 patients with unknown glucose regulation, 1835 (57.6%; 1400 men and 435 women) underwent an oral glucose tolerance test revealing that 17% of the men and 18% of the women had diabetes and 35 and 39% impaired glucose tolerance or impaired fasting glucose, respectively. Thus, only 19% of the women and 27% of the men had a normal glucose regulation. Women were more likely to have diabetes than men with an odds ratio (OR) of 1.32 (1.13–1.54). The corresponding OR for abnormal glucose regulation was 1.34 (1.11–1.62). Gender did not influence differences in clinical presentation between patients with diabetes or IGR and those with a normal glucose metabolism. Conclusion Abnormal glucose regulation was more common in women than men with CAD. However, the influence of diabetes on presenting symptoms and clinical course was similar in men and women.
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| 9. |
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| 10. |
- Halford, Christina, et al.
(författare)
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A population-based study of nearly 15 000 observations among Swedish women and men during 1973-2003
- 2012
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 2:6
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Global self-rated health (SRH) has become extensively used as an outcome measure in population health surveillance. The aim of this study was to analyse the effects of age and secular trend (year of investigation) on SRH.Design Prospective cohort study, using population-based data from eight ongoing cohort studies, with sampling performed between 1973 and 2003.Setting Sweden.Participants 11 880 women and men, aged 25–99 years, providing 14 470 observations.Primary outcome measure Global SRH.Results In multiple ordinal logistic regression analyses, adjusted for the effects of covariates, there were independent effects of age (p<0.0001) and of year of investigation (p<0.0001) on SRH. In women the association was linear, showing lower levels of SRH with increased age, and more recent year of investigation. In men the association was curvilinear, and thus more complex. The final model explained 76.2% of the SRH variance in women and 74.5% of the variance in men.Conclusions SRH was strongly and inversely associated with age in both sexes, after adjustment for other outcome-affecting variables. There was a strongly significant effect of year of investigation indicating a change in SRH, in women towards lower levels over calendar time, in men with fluctuations across time.
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