| 1. |
- Eriksson, Jan W, et al.
(författare)
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Hydrochlorothiazide, but not Candesartan, aggravates insulin resistance and causes visceral and hepatic fat accumulation : the mechanisms for the diabetes preventing effect of Candesartan (MEDICA) Study
- 2008
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Ingår i: Hypertension. - 0194-911X. ; 52:6, s. 1030-1037
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Tidskriftsartikel (refereegranskat)abstract
- Treatment with angiotensin II receptor blockers is associated with lower risk for the development of type 2 diabetes mellitus compared with thiazide diuretics. The Mechanisms for the Diabetes Preventing Effect of Candesartan Study addressed insulin action and secretion and body fat distribution after treatment with candesartan, hydrochlorothiazide, and placebo. Twenty-six nondiabetic, abdominally obese, hypertensive patients were included in a multicenter 3-way crossover trial, and 22 completers (by predefined criteria; 10 men and 12 women) were included in the analyses. They underwent 12-week treatment periods with candesartan (C; 16 to 32 mg), hydrochlorothiazide (H; 25 to 50 mg), and placebo (P), respectively, and the treatment order was randomly assigned and double blinded. Intravenous glucose tolerance tests and euglycemic hyperinsulinemic (56 mU/m(2) per minute) clamps were performed. Intrahepatic and intramyocellular and extramyocellular lipid content and subcutaneous and visceral abdominal adipose tissue were measured using proton magnetic resonance spectroscopy and MRI. Insulin sensitivity (M-value) was reduced following H versus C and P (6.07+/-2.05, 6.63+/-2.04, and 6.90+/-2.10 mg/kg of body weight per minute, mean+/-SD; P<or=0.01). Liver fat content was higher (P<0.05) following H than both P and C. The subcutaneous to visceral abdominal adipose tissue ratio was reduced following H versus C and P (P<0.01). Glycosylated hemoglobin, alanine aminotransferase, aspartate aminotransferase, and high-sensitivity C-reactive protein levels were higher (P<0.05) after H, but not C, versus P. There were no changes in body fat, intramyocellular lipid, extramyocellular lipid, or first-phase insulin secretion. Blood pressure was reduced similarly by C and H versus P. In conclusion, visceral fat redistribution, liver fat accumulation, low-grade inflammation, and aggravated insulin resistance were demonstrated after hydrochlorothiazide but not candesartan treatment. These findings can partly explain the diabetogenic potential of thiazides.
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| 2. |
- Farrohknia, Nasim, et al.
(författare)
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Emergency department triage scales and their components : a systematic review of the scientific evidence.
- 2011
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Ingår i: Scandinavian journal of trauma, resuscitation and emergency medicine. - 1757-7241. ; 19, s. 42
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Tidskriftsartikel (refereegranskat)abstract
- Emergency department (ED) triage is used to identify patients' level of urgency and treat them based on their triage level. The global advancement of triage scales in the past two decades has generated considerable research on the validity and reliability of these scales. This systematic review aims to investigate the scientific evidence for published ED triage scales. The following questions are addressed: 1. Does assessment of individual vital signs or chief complaints affect mortality during the hospital stay or within 30 days after arrival at the ED?2. What is the level of agreement between clinicians' triage decisions compared to each other or to a gold standard for each scale (reliability)? 3. How valid is each triage scale in predicting hospitalization and hospital mortality? A systematic search of the international literature published from 1966 through March 31, 2009 explored the British Nursing Index, Business Source Premier, CINAHL, Cochrane Library, EMBASE, and PubMed. Inclusion was limited to controlled studies of adult patients (≥ 15 years) visiting EDs for somatic reasons. Outcome variables were death in ED or hospital and need for hospitalization (validity). Methodological quality and clinical relevance of each study were rated as high, medium, or low. The results from the studies that met the inclusion criteria and quality standards were synthesized applying the internationally developed GRADE system. Each conclusion was then assessed as having strong, moderately strong, limited, or insufficient scientific evidence. If studies were not available, this was also noted.We found ED triage scales to be supported, at best, by limited and often insufficient evidence.The ability of the individual vital signs included in the different scales to predict outcome is seldom, if at all, studied in the ED setting. The scientific evidence to assess interrater agreement (reliability) was limited for one triage scale and insufficient or lacking for all other scales. Two of the scales yielded limited scientific evidence, and one scale yielded insufficient evidence, on which to assess the risk of early death or hospitalization in patients assigned to the two lowest triage levels on a 5-level scale (validity).
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| 3. |
- Holmlund, Anders, et al.
(författare)
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Porphyromonas gingivalis (Pg) a possible link between impaired oral health and acute myocardial infarction
- 2011
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Ingår i: International Journal of Cardiology. - 0167-5273. ; 148:2, s. 148-153
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate if oral health parameters were impaired in patients with myocardial infarction (MI) and if there was an association with serum antibody levels against the periodontal pathogens Porphyromonas gingivalis (Pg) and Aggregatibacter actinomycetemcomitans (Aa). Methods: A case-control study consisting of 100 patients with MI and 100 age- and sex-matched controls from the same geographic area was investigated regarding oral health. Results: The MI group had significantly more periodontal bone loss (PBL), number of deepened pockets (NDP), and bleeding on probing (BOP), and lower number of teeth (NT) than the controls. After adjustment for known cardiovascular risk factors NT, BOP, and NDP still remained significantly related to MI (p = 0.014, p = 0.02, and p = 0.0069, respectively). IgG antibody levels against Pg were higher in subjects with MI (p = 0.043), as well as in those with > 4 deepened pockets (p = 0.05), BOP > 20% (p = 0.001) and PBL (p = 0.0003). However, indicating a causal pathway, the relationship between MI and Pg IgG disappeared when the oral parameters were included in the logistic regression model (p = 0.69). No correlation was seen between MI and Aa in the present study. Conclusion: Patients with MI had an impaired oral health compared to controls. Furthermore, IgG levels against Pg were related to both MI and oral health, suggesting this pathogen as a possible link between oral health and CVD.
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| 4. |
- Deloukas, Panos, et al.
(författare)
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Large-scale association analysis identifies new risk loci for coronary artery disease
- 2013
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Ingår i: Nature Genetics. - 1061-4036. ; 45:1, s. 25-33
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Tidskriftsartikel (refereegranskat)abstract
- Coronary artery disease (CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CAD cases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants (r2 < 0.2) strongly associated with CAD at a 5% false discovery rate (FDR). Together, these variants explain approximately 10.6% of CAD heritability. Of the 46 genome-wide significant lead SNPs, 12 show a significant association with a lipid trait, and 5 show a significant association with blood pressure, but none is significantly associated with diabetes. Network analysis with 233 candidate genes (loci at 10% FDR) generated 5 interaction networks comprising 85% of these putative genes involved in CAD. The four most significant pathways mapping to these networks are linked to lipid metabolism and inflammation, underscoring the causal role of these activities in the genetic etiology of CAD. Our study provides insights into the genetic basis of CAD and identifies key biological pathways.
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| 5. |
- Dupuis, Josee, et al.
(författare)
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New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk
- 2010
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Ingår i: Nature Genetics. - 1061-4036. ; 42:2, s. 105-116
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Tidskriftsartikel (refereegranskat)abstract
- Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.
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| 6. |
- Manning, Alisa K., et al.
(författare)
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A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance
- 2012
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Ingår i: Nature Genetics. - New York : Nature Publishing Group. - 1061-4036. ; 44:6, s. 659-669
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Tidskriftsartikel (refereegranskat)abstract
- Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and beta-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci associated with fasting insulin at P < 5 x 10(-8) in combined discovery and follow-up analyses of 52 studies comprising up to 96,496 non-diabetic individuals. Risk variants were associated with higher triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci in insulin resistance pathways. The discovery of these loci will aid further characterization of the role of insulin resistance in T2D pathophysiology.
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| 7. |
- Mirza, Majd, et al.
(författare)
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Circulating fibroblast growth factor-23 is associated with fat mass and dyslipidemia in two independent cohorts of elderly individuals
- 2011
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - 1079-5642. ; 31:1, s. 219-227
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Tidskriftsartikel (refereegranskat)abstract
- Background:Disturbances in mineral metabolism define an increased cardiovascular risk in patients with chronic kidney disease. Fibroblast growth factor-23 (FGF23) is a circulating regulator of phosphate and vitamin D metabolism, and has recently been implied as a putative pathogenic factor in cardiovascular disease. Since other members of the fibroblast growth factor (FGF) family play a role in lipid and glucose metabolism, we hypothesized that FGF23 would associate with metabolic factors that predispose to an increased cardiovascular risk.Aim: To investigate the relation between FGF23 and metabolic cardiovascular risk factors in the community.Methods and Results: Relations between serum FGF23 and body mass index (BMI), waist circumference, waist-to-hip ratio, serum lipids and fat mass were examined in two community-based, cross-sectional cohorts of elderly Caucasians (MrOS: 964 men aged 75 ± 3.2 and PIVUS: 946 men and women aged 70). In both cohorts, FGF23 associated negatively with high-density lipoprotein and apolipoprotein A1 (7-21% decrease per 1-SD increase in log FGF23; p<0.01) and positively with triglycerides (11-14% per 1-SD increase in log FGF23; p<0.01). 1-SD increase in log FGF23 was associated with a 7-20% increase in BMI, waist circumference and waist-to-hip ratio and a 7-18% increase in trunk and total body fat mass (p<0.01) as determined by whole-body dual x-ray absorptiometry. FGF23 levels were higher in subjects with the metabolic syndrome compared to those without (46.4 versus 41.2 pg/mL; p<0.05) and associated with an increased risk of having the metabolic syndrome (OR per 1-SD increase in log FGF23, 1.21; 95% CI, 1.04 to 1.40, p<0.05).Conclusions: We for the first time report on associations between circulating FGF23, fat mass and adverse lipid metabolism resembling the metabolic syndrome, potentially representing novel pathway(s) linking high FGF23 to an increased cardiovascular risk.
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| 8. |
- Schölin, Anna, et al.
(författare)
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CRP and IL-6 concentrations are associated with poor glycemic control despite preserved beta-cell function during the first year after diagnosis of type 1 diabetes.
- 2004
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Ingår i: Diabetes Metab Res Rev. - 1520-7552. ; 20:3, s. 205-10
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Tidskriftsartikel (refereegranskat)abstract
- Background The role of non-specific inflammation in beta-cell loss in type 1 diabetes is unclear. in the present study, inflammatory markers were determined in patients with newly diagnosed disease and related to beta-cell function, glycemic control and autoimmunity. Methods Ninety-seven adult patients with type 1 diabetes mellitus (80% islet antibody positives, ab(+)) were examined at diagnosis and 3, 6, 9 and 12 months after the start of insulin treatment. Plasma C-reactive protein (CRP), interleukin-6 (IL-6), C-peptide, islet autoantibodies, insulin requirement and HbA(1c) were assessed. Results The concentrations of CRP were high-normal at diagnosis and did not change during the study period. A positive correlation between CRP at diagnosis and BMI was observed in ab(+) as well as in ab(+) cases. Detectable concentrations of IL-6 were found in 32% (157/485) of the samples and did not change during the study. Ab(-) patients had higher values of CRP at diagnosis and throughout the study compared to the ab(+). Among the ab(+) patients, CRP concentrations during the study were positively correlated to C-peptide at 12 months and an increase in HbA(1c), levels between 6 and 12 months. No associations between the presence or levels of islet autoantibodies and CRP were noted. Conclusions In type 1 diabetes, the islet destructive process and the development of beta-cell remission are not associated with changes in CRP or IL-6. instead, elevated CRP concentrations are prevalent and seem to reflect insulin resistance, as positive associations to BMI, C-peptide and deterioration of glycemic control were observed. Copyright (C) 2004 John Wiley Sons, Ltd.
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| 9. |
- Scott, Robert A., et al.
(författare)
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Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways
- 2012
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Ingår i: Nature Genetics. - Nature Publishing Group. - 1061-4036. ; 44:9, s. 991-1005
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Tidskriftsartikel (refereegranskat)abstract
- Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control.
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| 10. |
- Arefalk, Gabriel, et al.
(författare)
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Smokeless tobacco (snus) and risk of heart failure : results from two Swedish cohorts
- 2012
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Ingår i: European Journal of Cardiovascular Prevention & Rehabilitation. - 1741-8267. ; 19:5, s. 1120-1127
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Tidskriftsartikel (refereegranskat)abstract
- Background:Oral moist snuff (snus) is discussed as a safer alternative to smoking, and its use is increasing. Based on its documented effect on blood pressure, we hypothesized that use of snus increases the risk of heart failure.Design:Two independent Swedish prospective cohorts; the Uppsala Longitudinal Study of Adult Men (ULSAM), a community-based sample of 1076 elderly men, and the Construction Workers Cohort (CWC), a sample of 118,425 never-smoking male construction workers.Methods:Cox proportional hazards models were used to investigate possible associations of snus use with risk of a first hospitalization for heart failure.Results: In ULSAM, 95 men were hospitalized for heart failure, during a median follow up of 8.9 years. In a model adjusted for established risk factors including past and present smoking exposure, current snus use was associated with a higher risk of heart failure [hazard ratio (HR) 2.08, 95% confidence interval (CI) 1.03-4.22] relative to non-use. Snus use was particularly associated with risk of non-ischaemic heart failure (HR 2.55, 95% CI 1.12-5.82). In CWC, 545 men were hospitalized for heart failure, during a median follow up of 18 years. In multivariable-adjusted models, current snus use was moderately associated with a higher risk of heart failure (HR 1.28, 95% CI 1.00-1.64) and non-ischaemic heart failure (HR 1.28, 95% CI 0.97-1.68) relative to never tobacco use.Conclusion:Data from two independent cohorts suggest that use of snus may be associated with a higher risk of heart failure.
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