| 1. |
- Al-Majdoub, Mahmoud, et al.
(författare)
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Population-level analysis to determine parameters that drive variation in the plasma metabolite profiles
- 2018
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Ingår i: Metabolites. - : MDPI AG. - 2218-1989. ; 8:4
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Tidskriftsartikel (refereegranskat)abstract
- The plasma metabolome is associated with multiple phenotypes and diseases. However, a systematic study investigating clinical determinants that control the metabolome has not yet been conducted. In the present study, therefore, we aimed to identify the major determinants of the plasma metabolite profile. We used ultra-high performance liquid chromatography (UHPLC) coupled to quadrupole time of flight mass spectrometry (QTOF-MS) to determine 106 metabolites in plasma samples from 2503 subjects in a cross-sectional study. We investigated the correlation structure of the metabolite profiles and generated uncorrelated metabolite factors using principal component analysis (PCA) and varimax rotation. Finally, we investigated associations between these factors and 34 clinical covariates. Our results suggest that liver function, followed by kidney function and insulin resistance show the strongest associations with the plasma metabolite profile. The association of specific phenotypes with several components may suggest multiple independent metabolic mechanisms, which is further supported by the composition of the associated factors. © 2018 by the authors. Licensee MDPI, Basel, Switzerland.
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| 2. |
- Andersson, Susanne, 1957, et al.
(författare)
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The association between self-rated health and impaired glucose tolerance in Swedish adults: A cross-sectional study
- 2013
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Ingår i: Scandinavian Journal of Primary Health Care. - : Informa UK Limited. - 0281-3432 .- 1502-7724. ; 31:2, s. 111-118
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To investigate gender differences in the association between self-rated health (SRH) and impaired glucose tolerance (IGT) in subjects unaware of their glucose tolerance. Design. A cross-sectional population-based study. Setting. The two municipalities of Vara and Skövde in south-western Sweden. Subjects. A total of 2502 participants (1301 women and 1201 men), aged 30–75, were randomly selected from the population. Main outcome measures. IGT was regarded as the outcome measure and SRH as the main risk factor. Results. The prevalence of IGT was significantly higher in women (11.9%) than in men (10.1%), (p = 0.029), as was the prevalence of low SRH (women: 35.4%; men: 22.1%, p = 0.006). Both men and women with low SRH had a poorer risk factor profile than those with high SRH, and a statistically significant crude association between SRH and IGT was found in both men (OR = 2.8, 95% CI 1.8–4.4) and women (OR = 1.5, 95% CI 1.0–2.2, p = 0.033). However, after controlling for several lifestyle factors and biomedical variables, the association was attenuated and remained statistically significant solely in men (OR = 2.3, 95% CI 1.2–4.3). Conclusion. The gender-specific associations found between SRH and IGT suggest that SRH may be a better indicator of IGT in men than in women. Future studies should evaluate the utility of SRH in comparison with objective health measures as a potential aid to health practitioners when deciding whether to screen for IGT and T2DM.
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| 3. |
- Bollano, Entela, 1970, et al.
(författare)
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Early post-transplant elevated pulmonary artery pressure predicts adverse outcome in cardiac recipients.
- 2020
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Ingår i: International Journal of Cardiology. Heart & vasculature. - : Elsevier BV. - 2352-9067. ; 26
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the prognostic value of early post-transplant hemodynamic measurements on 5-year mortality in cardiac recipients (HTx).A right heart catheterization was performed in 290 heart transplantation (HTx) recipients at a one-year post-HTx evaluation. To study the effect of post-HTx hemodynamic variables on 5-year outcome, the cohort was stratified into several subgroups. For right atrial pressure (RAP), mean pulmonary artery pressure (MPAP), pulmonary artery wedge pressure (PAWP), and pulmonary vascular resistance (PVR), patients with values from the upper 10th percentile (high), were compared with those with values from the remaining lower 90th percentile (normal). For cardiac index (CI), patients with values from the lower 10th percentile (low) were compared with those with values from the remaining upper 90th percentile (normal).Death or re-transplantation within 5 years after the one-year control occurred in 44 patients (13%). Of those, death or re-HTx was related to graft failure in 20 of cases (45%) and non-cardiac causes in 24 of cases (55%). The risk of death or re-HTx was higher in the subgroup with MPAP above 23 mmHg than those equal to or below this value [hazard ratio 3.22, 95% confidence interval (CI) 1.49-6.97; P = 0.003]. The association remained significant despite adjustment for several comorbidities. There were no differences in outcome between subgroups stratified with respect to high versus low RAP, PAWP, CI or PVR.Elevated pulmonary artery pressure at a first annual evaluation after HTx was the only hemodynamic variable that predicted impaired outcome in cardiac recipients.
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| 4. |
- Buschard, Karsten, et al.
(författare)
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Sulfatide and Longevity
- 2022
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Ingår i: The journals of gerontology. Series A, Biological sciences and medical sciences. - : Oxford University Press (OUP). - 1758-535X. ; 77:9, s. 1715-1716
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Tidskriftsartikel (refereegranskat)
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| 5. |
- Daka, Bledar, et al.
(författare)
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Association between self-reported alcohol consumption and diastolic dysfunction: a cross-sectional study
- 2023
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Ingår i: Bmj Open. - 2044-6055. ; 13:10
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Tidskriftsartikel (refereegranskat)abstract
- Background and objectives While alcohol consumption is associated with common risk factors for diastolic dysfunction the independent impact of low levels of alcohol consumption on this condition in a community setting is still unclear. Thus, the aim of this study was to explore this association in a representative population sample employing optimal echocardiographic techniques.Background and objectives While alcohol consumption is associated with common risk factors for diastolic dysfunction the independent impact of low levels of alcohol consumption on this condition in a community setting is still unclear. Thus, the aim of this study was to explore this association in a representative population sample employing optimal echocardiographic techniques.Design Cross-sectional observational study in community-based population.Settings, participants and methods Participants between 30 and 75 years of age were consecutively invited to a physical examination, interview, conventional echocardiography, including Tissue Velocity Imaging. Diastolic dysfunction was defined according to the European Society of Cardiology criteria, excluding subjects with ejection fraction <45%, self-reported history of heart failure or atrial fibrillation on ECG. Self-reported alcohol intake using a validated questionnaire was categorised as no intake, low and medium-high intake.Results In total, 500 men and 538 women (mean age 55.4 +/- 13) were successfully examined. Diastolic dysfunction was identified in 16% (79/500) of the men and 13% (58/538) of the women. The multivariable adjusted model revealed a strong and independent association between alcohol intake and diastolic dysfunction. In fact, using no alcohol intake as reference, diastolic dysfunction was independently associated with alcohol consumption in a dose-dependent fashion; low consumption, OR 2.3 (95% CI 1.3 to 4.0) and medium-high consumption OR 3.1 (95% CI 1.6 to 6.2), respectively.Conclusion There was a significant association between alcohol consumption and diastolic dysfunction starting already at low levels that was supported by a dose-dependent pattern. These results need confirmatory studies and are important in public health policies.
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| 6. |
- Daka, Bledar, et al.
(författare)
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Circulating concentrations of endothelin-1 predict coronary heart disease in women but not in men: A longitudinal observational study in the Vara-Skövde Cohort
- 2015
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Ingår i: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- © 2015 Daka et al.Background: The vasoconstricting peptide endothelin-1 has been proposed to be a marker of cardiovascular disease. Our aim was to investigate whether circulating endothelin-1 levels predict coronary heart disease (CHD) in Sweden. Methods: In 2002-2005, 2816 adult participants (30-74 years) were randomly selected from two municipalities in south-western Sweden. Cardiovascular risk factors and endothelin-1 levels were assessed at baseline, and incident CHD was followed-up in all participants through 2011. After exclusion of 50 participants due to known CHD at baseline and 21 participants because of unsuccessful analysis of endothelin-1, 2745 participants were included in the study. In total, 72 CHD events (52 in men and 20 in women) were registered during the follow-up time. Results: We showed that baseline circulating endothelin-1 levels were higher in women with incident CHD than in women without CHD (3.2 pg/ml, SE: 0.36 vs 2.4 pg/ml, SE: 0.03, p = 0.003) whereas this difference was not observed in men (2.3 pg/ml, SE: 0.16 vs 2.3 pg/ml, SE: 0.04, p = 0.828). An age-adjusted Cox proportional regression analysis showed an enhanced risk of CHD with increasing baseline endothelin-1 levels in women (hazard ratio (HR) = 1.51, 95 % CI = 1.1-2.1, p = 0.015) but not in men (HR = 0.98, 95 % CI = 0.8-1.2, p = 0.854). Furthermore, the predictive value of endothelin-1 for incident CHD in women was still significant after adjustments for age, HOMA-IR, apolipoprotein (apo)B/apoA1 and smoking (HR = 1.53, CI = 1.1-1.2, p = 0.024). Conclusion: Circulating endothelin-1 levels may predict CHD in women.
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| 7. |
- Daka, Bledar, et al.
(författare)
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Inverse association between serum insulin and sex hormone-binding globulin in a population survey in Sweden
- 2013
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Ingår i: Endocrine Connections. - 2049-3614. ; 2:1, s. 18-22
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Obesity is associated with low levels of sex hormone-binding globulin (SHBG). While the reason is not fully understood, we aimed to study the association between serum insulin and levels of SHBG in a random population. DESIGN AND METHODS: Between 2001 and 2005, a random sample of 2816 participants aged 30-74 years were enrolled in a cross-sectional survey in the South-west of Sweden. Fasting blood samples were collected and an oral glucose tolerance test (OGTT) was conducted in all subjects without known diabetes. Diabetes mellitus was defined according to criteria from WHO, and clinical characteristics were used to discriminate between type 1 (T1D) and type 2 diabetes (T2D). Analyses of SHBG were successful in 2782 participants (98%), who thus constituted the current study population. RESULTS: WE FOUND SIGNIFICANT INVERSE ASSOCIATION BETWEEN LEVELS OF SHBG AND FASTING SERUM INSULIN IN BOTH GENDERS (MEN: β=-0.090, P=0.001; women: β=-0.197, P<0.001), which was independent of differences in age and BMI. The associations remained when also differences in fasting plasma glucose were accounted for (men: β=-0.062, P=0.022; women: β=-0.176, P≤0.001). Subjects with T1D exhibited higher levels of SHBG than both T2D (men: δ=15.9 nmol/l, P<0.001; women: δ=71.1 nmol/l, P<0.001) and non-diabetic subjects (men: δ=15.1 nmol/l, P<0.001; women: δ=72.9 nmol/l, P<0.001) independent of age, BMI and fasting glucose levels. CONCLUSION: These findings are consistent with high levels of SHBG in T1D, and correspondingly low levels in T2D subjects, suggesting an inhibitory effect of insulin on the SHBG production in the liver.
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| 8. |
- Daka, Bledar, et al.
(författare)
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Low agreement between radio binding assays in analyzing glutamic acid decarboxylase (GAD65Ab) autoantibodies in patients classified with type 2 diabetes.
- 2009
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Ingår i: Autoimmunity. - : Informa UK Limited. - 1607-842X .- 0891-6934. ; 42:6, s. 507-14
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Tidskriftsartikel (refereegranskat)abstract
- Autoantibodies against glutamic acid decarboxylase (GAD65Ab) are used in the classification of diabetes in adults. We assessed the concordance in GAD65 autoantibody levels within subjects between three different GAD65Ab radio binding assays (RBA). Plasma samples from 112 diabetes patients (median age 50 years) initially classified with type 2 diabetes was randomly selected from a local diabetes registry. Coded samples were analyzed with two RBA employing (35)S-labeled GAD65. The first used the pEx9 plasmid (pEx9 RBA), the second employed the pThGAD65 plasmid (pThGAD65 RBA) to label GAD65 by in vitro transcription translation. We also used a commercial kit employing plasmid pGAD17 labelled with (125)I (pGAD17 RBA). Subsequent analyses followed standard procedures. Two different cut-offs for GAD65Ab positivity were used in all three assays. We calculated the correlation, concordance, and agreement between the assays. The proportion of GAD65Ab positivity differed between assays when low cut-offs were used (pEx9 RBA 25%, pThGAD65 RBA 17.9%, and pGAD17 RBA 12.5%, respectively). When high cut-offs were applied, the concordance between the pEx9 RBA and the pThGAD65 RBA was 97.3 while their concordance to the pGAD17 RBA was lower (88.4 and 87.4, respectively). There was a low agreement between both pEx9 RBA and pGAD17 RBA (0.45, 95% CI 0.20-0.70) and between pThGAD65 RBA and pGAD17 RBA (0.43, 95% CI 0.18-0.68). We found discrepancies in determining the GAD65Ab positivity, which constitutes a problem when GAD65Ab are used clinically. Further methodological GAD65Ab assays studies are warranted.
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| 9. |
- Daka, Bledar, et al.
(författare)
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Low concentrations of serum testosterone predict acute myocardial infarction in men with type 2 diabetes mellitus
- 2015
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Ingår i: Bmc Endocrine Disorders. - : Springer Science and Business Media LLC. - 1472-6823. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aim of the present study was to investigate the associations between endogenous testosterone concentrations and the incidence of acute myocardial infarction (AMI) in men and women with and without type 2 diabetes. Methods: The study comprised 1109 subjects >= 40 years of age (mean age 62 +/- 12 years) participating in a baseline survey in Sweden in 1993-94. Information about smoking habits and physical activity was obtained using validated questionnaires. Serum concentrations of testosterone and sex hormone-binding globulin (SHBG) were obtained using radioimmunoassay. Diagnosis of type 2 diabetes was based on WHO's 1985 criteria. Individual patient information on incident AMI was ascertained by record linkage with national inpatient and mortality registers from baseline through 2011. Results: The prevalence of type 2 diabetes at baseline was 10.0 % in men and 7.5 % in women. During a mean follow-up of 14.1 years (+/- 5.3), there were 74 events of AMI in men and 58 in women. In age-adjusted Cox models, a significant inverse association between concentrations of testosterone and AMI-morbidity was found in men with type 2 diabetes (HR = 0.86 CI (0.75-0.98)). In a final model also including waist-to-hip ratio, systolic blood pressure, total cholesterol and active smoking, the association still remained statistically significant (HR = 0.754 CI (0.61-0.92)). Conclusion: Low concentrations of testosterone predicted AMI in men with type 2 diabetes independent of other risk factors. Trials with testosterone investigating the effect regarding cardiovascular outcome are still lacking. Future trials in this field should take into account a modification effect of diabetes.
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| 10. |
- Daka, Bledar, et al.
(författare)
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Low sex hormone-binding globulin is associated with hypertension: a cross-sectional study in a Swedish population
- 2013
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Ingår i: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aim of this study was to investigate the association of sex hormone-binding globulin (SHBG) and hypertension in a Swedish population. Methods: The study is based on a random sample of a Swedish population of men and women aged 30-74 years (n=2,816). Total testosterone, oestradiol and SHBG were measured in 2,782 participants. Free androgen index was then calculated according to the formula FAI=100 x (Total testosterone)/SHBG. Hypertension was diagnosed according to JNC7. Results: In men, but not in women, significant association between SHBG and both diastolic (diastolic blood pressure: beta=-0.143 p<0.001) and systolic blood pressure (systolic blood pressure beta=-0.114 p<0.001) was found. The association was still significant after adjusting for age, body mass index (BMI), homeostatic model assessment insulin resistance (HOMA-IR), triglycerides, high density lipoproteins (HDL) and C-reactive protein (CRP) (diastolic blood pressure: beta=-0.113 p<0.001; systolic blood pressure beta=-0.093 p=0.001). An inverse association was observed between SHBG and hypertension in both men (B=-0.024 p<0.001) and women (B=-0.022 p<0.001). The association was still significant in women older than 50 years after adjustments for age, BMI, physical activity, CRP and alcohol consumption (B=-0.014, p=0.008). Conclusion: In conclusion, these results show a strong association between SHBG and blood pressure independent of major determinants of high blood pressure. This association might be addressed to direct effects of SHBG in endothelial cells through the receptor for SHBG. If this is confirmed by other observational and experimental studies, it might become a new field for the development of therapies for lowering blood pressure.
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