| 1. |
- Aaseth, Jan, et al.
(författare)
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Diets and drugs for weight loss and health in obesity : An update
- 2021
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Ingår i: Biomedicine and Pharmacotherapy. - : Elsevier France ; Editions Scientifiques Medicales. - 0753-3322 .- 1950-6007. ; 140
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Forskningsöversikt (refereegranskat)abstract
- Numerous combinations of diets and pharmacological agents, including lifestyle changes, have been launched to treat obesity. There are still ambiguities regarding the efficacies of different approaches despite many clinical trials and the use of animal models to study physiological mechanisms in weight management and obesity comorbidities, Here, we present an update on promising diets and pharmacological aids. Literature published after the year 2005 was searched in PubMed, Medline and Google scholar. Among recommended diets are low-fat (LF) and low-carbohydrate (LC) diets, in addition to the Mediterranean diet and the intermittent fasting approach, all of which presumably being optimized by adequate contents of dietary fibers. A basic point for weight loss is to adopt a diet that creates a permanently negative and acceptable energy balance, and prolonged dietary adherence is a crucial factor. As for pharmacological aids, obese patients with type 2 diabetes or insulin resistance seem to benefit from LC diet combined with a GLP-1 agonist, e.g. semaglutide, which may improve glycemic control, stimulate satiety, and suppress appetite. The lipase inhibitor orlistat is still used to maintain a low-fat approach, which may be favorable e.g. in hypercholesterolemia. The bupropion-naltrexone-combination appears promising for interruption of the vicious cycle of addictive over-eating. Successful weight loss seems to improve almost all biomarkers of obesity comorbidities. Until more support for specific strategies is available, clinicians should recommend an adapted lifestyle, and when necessary, a drug combination tailored to individual needs and comorbidities. Different diets may change hormonal secretion, gut-brain signaling, and influence hunger, satiety and energy expenditure. Further research is needed to clarify mechanisms and how such knowledge can be used in weight management.
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| 2. |
- Aaseth, Jan, et al.
(författare)
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The Aging Kidney-As Influenced by Heavy Metal Exposure and Selenium Supplementation
- 2021
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Ingår i: Biomolecules. - : MDPI. - 2218-273X. ; 11:8
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Tidskriftsartikel (refereegranskat)abstract
- The aging process in the kidneys has been well studied. It is known that the glomerular filtration rate (GFR) declines with age in subjects older than 50-60 years. However, there is still insufficient knowledge regarding the response of the aged kidney to environmental toxicants such as mercury, cadmium, and lead. Here, we present a review on the functional decline and proposed mechanisms in the aging kidney as influenced by metal pollutants. Due to the prevalence of these toxicants in the environment, human exposure is nearly unavoidable. Further, it is well known that acute and chronic exposures to toxic metals may be detrimental to kidneys of normal adults, thus it may be hypothesized that exposure of individuals with reduced GFR will result in additional reductions in renal function. Individuals with compromised renal function, either from aging or from a combination of aging and disease, may be particularly susceptible to environmental toxicants. The available data appear to show an association between exposure to mercury, cadmium and/or lead and an increase in incidence and severity of renal disease in elderly individuals. Furthermore, some physiological thiols, as well as adequate selenium status, appear to exert a protective action. Further studies providing improved insight into the mechanisms by which nephrotoxic metals are handled by aging kidneys, as well as possibilities of therapeutic protection, are of utmost importance.
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| 3. |
- Alehagen, Urban, 1951-, et al.
(författare)
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Dietary Supplementation with Selenium and Coenzyme Q10 Prevents Increase in Plasma D-Dimer While Lowering Cardiovascular Mortality in an Elderly Swedish Population.
- 2021
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Ingår i: Nutrients. - Basel : MDPI. - 2072-6643. ; 13:4, s. 43-56
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Tidskriftsartikel (refereegranskat)abstract
- A low intake of selenium is associated with increased cardiovascular mortality. This could be reduced by supplementation with selenium and coenzyme Q10. D-dimer, a fragment of fibrin mirroring fibrinolysis, is a biomarker of thromboembolism, increased inflammation, endothelial dysfunction and is associated with cardiovascular mortality in ischemic heart disease. The objective was to examine the impact of selenium and coenzyme Q10 on the level of D-dimer, and its relationship to cardiovascular mortality. D-dimer was measured in 213 individuals at the start and after 48 months of a randomised double-blind placebo-controlled trial with selenium yeast (200 µg/day) and coenzyme Q10 (200 mg/day) (n = 106) or placebo (n = 107). The follow-up time was 4.9 years. All included individuals were low in selenium (mean 67 μg/L, SD 16.8). The differences in D-dimer concentration were evaluated by the use of T-tests, repeated measures of variance and ANCOVA analyses. At the end, a significantly lower D-dimer concentration was observed in the active treatment group in comparison with those on placebo (p = 0.006). Although D-dimer values at baseline were weakly associated with high-sensitive CRP, while being more strongly associated with soluble tumour necrosis factor receptor 1 and sP-selectin, controlling for these in the analysis there was an independent effect on D-dimer. In participants with a D-dimer level above median at baseline, the supplementation resulted in significantly lower cardiovascular mortality compared to those on placebo (p = 0.014). All results were validated with a persisting significant difference between the two groups. Therefore, supplementation with selenium and coenzyme Q10 in a group of elderly low in selenium and coenzyme Q10 prevented an increase in D-dimer and reduced the risk of cardiovascular mortality in comparison with the placebo group. The obtained results also illustrate important associations between inflammation, endothelial function and cardiovascular risk.
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| 4. |
- Alehagen, Urban, 1951-, et al.
(författare)
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Elevated D-dimer level is an independent risk factor for cardiovascular death in out-patients with symptoms compatible with heart failure
- 2004
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Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 92:6, s. 1250-1258
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Tidskriftsartikel (refereegranskat)abstract
- D-dimer, a marker of fibrin turnover, exhibits many interesting properties as a biological marker of thrombosis. Some of the properties of D-dimer might also be used to provide additional information about patients with heart failure. In this study, we evaluate the prognostic information acquired from D-dimer concerning increased risk of cardiovascular mortality in an elderly population with symptoms associated with heart failure. A cardiologist examined 458 elderly patients, out of 548 invited, attending primary care for symptoms of dyspnoea, fatigue and/or peripheral oedema and assessed NYHA functional class and cardiac function. Abnormal systolic function was defined as EF <40% on Doppler echocardiography. Abnormal diastolic function was defined as reduced E/A ratio and/or an abnormal pattern of pulmonary venous flow. Blood samples were drawn, and BNP and D-dimer were analysed. D-dimer was analysed using an automated micro-latex assay. A statistical analysis was performed to identify the prognostic value of increased plasma concentration of D-dimer. Results showed that during a median follow-up period of 5.5 years, 68 (14%) patients died of cardiovascular disease. No gender difference was noted. A plasma concentration of D-dimer >0.25mg/L increased the risk almost 4-fold. In conclusion, D-dimer is an independent risk factor for cardiovascular mortality that may be used to risk-stratify patients with heart failure. © 2004 Schattauer GmbH, Stuttgart.
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| 5. |
- Alehagen, Urban, 1951-, et al.
(författare)
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Genetic variance and plasma concentration of CD93 is associated with cardiovascular mortality : Results from a 6.7-year follow-up of a healthy community-living elderly population
- 2020
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Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997 .- 1791-3004. ; 22:6, s. 4629-4636
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Tidskriftsartikel (refereegranskat)abstract
- Inflammation is one of the fundamental processes in numerous diseases. Cluster of differentiation (CD) 93, a glycoprotein, has been reported to be associated with a number of these diseases. There are reports indicating that a high plasma level of CD93 is associated with adverse events in ischaemic heart disease. Additionally, there are reports indicating different cardiovascular risks between different single nucleotide polymorphisms (SNPs) of CD93. Therefore, the present study aimed to determine whether the plasma concentration of CD93 and polymorphism of rs2749812 in CD93 were associated with clinical conditions and mortality in an elderly population. In 470 healthy elderly community-living individuals a novel clinical examination involving echocardiography and blood sampling was performed. The population was followed for 6.7 years. Plasma levels of CD93 and SNP analyses of rs2749812 of CD93 using PCR methodology were used. During the follow-up period, 106 (22.6%) all-cause and 61 (13.0%) cardiovascular deaths were registered. Those with the highest plasma concentration had markedly higher all-cause mortality. Evaluating the A/A, A/G and G/G genotypes, the G/G group exhibited significantly higher cardiovascular mortality (P=0.026), and an almost two-fold increased risk in a multivariate Cox regression model compared with the A/G genotype. Evaluation of subgroups with respect to sex, diabetes and hypertension revealed markedly increased cardiovascular risk in the G/G genotype in all subgroups. All results persisted in the multiple models used. In the present study, the glycoprotein CD93 was demonstrated to have prognostic cardiovascular information, with increased risk for those with a high plasma concentration. Furthermore, the G/G genotype of rs2749812 of CD93 has a significantly higher cardiovascular risk, as demonstrated here, and could therefore be regarded as a possible cardiovascular risk biomarker that might in the future be used to offer optimised cardiovascular patient handling. However, this was a small study, and more research is required.
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| 6. |
- Alehagen, Urban, 1951-
(författare)
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Heart failure in primary health care : special emphasis on natriuretic peptides in the elderly
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: This thesis focuses on heart failure among elderly patients in the community who usually are not included in studies on heart failure. The heart failure syndrome is an increasing problem in Western society. Severe heart failure is often easy to diagnose compared with light to moderate heart failure, which is more frequent in patients in the community,Doppler echocardiography is the most commonly used method to objectively verify an abnormal cardiac function, mostly the systolic function. One goal of this thesis was to evaluate both the systolic and diastolic functions. Another goal was a study of the possible utility of the B-type natriuretic peptide, BNP (brain natriuretic peptide), and the amino terminal fragment of its precursor, proBNP (N-terminal proBNP) as tools in the diagnosis of heart failure in elderly patients.Methods: In a primary health care setting, 510 elderly patients (age range 65-82 years) with symptoms and signs possibly associated with heart failure were examined concerning patient history, ongoing pharmacological treatment, clinical examination, chest x-ray, electrocardiogram, Doppler echo cardiography, and selected biochemical measurements of blood samples. Additionally, the natriuretic peptide BNP and the aminoterminal fragment of proBNP were analyzed for a possible influence of gender, age, impaired cardiac function assessed using Doppler echocardiography, other diseases, and phannacological treatment. We followed our study population for six years, carefully registering mortality with death certificates. This information was used in analyzing the risk of cardiovascular death based on Cox proportional hazard regression. We present a model for estimating the risk of cardiovascular death in the individual patient.Results: Almost half of our study population [mean age 73 (SD 6) years] with symptoms of possible heart failure had signs of impaired cardiac function on Doppler echocardiography. Half of these individuals had isolated impairment of the diastolic function. Almost two thirds of the elderly patients who had an ejection fraction of less than 40% did not receive treatment with ACE inhibitors, one of the cornerstones in the treatment of heart failure.BNP and N-terminal proBNP were equally effective in detecting impaired cardiac function. As a response to increased filling pressure they probably provide earlier information on the haemodynamic situation than Doppler echocardiography does.In these elderly patients, functional class (NYHA class III: 7 times increased risk), in vivo examination by Doppler echo cardiography (EF<30%: 8 times increased risk) and the in vitro measurement of plasma BNP (>27.8 pmol/L: 11 times increased risk) and N-terminal proBNP (>109 pmol/L: 7 times increased risk) could be used as prognostic determinants in assessing the risk of cardiovascular death.Conclusion: The results indicate that a focused patient history and clinical examination provides important information that is often sufficient for the prognostic evaluation of a patient with heart failure symptoms. Additional information may be obtained with Doppler echo cardiographic examination and measurement of plasma BNP or N-terminal proBNP. The relationship between BNPIN-terminal proBNP concentration and risk of cardiovascular death may be analysed to define decision limits for the concentrations of these peptides as regards further diagnostic procedures and/or phannaceutical treatment.
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| 7. |
- Alehagen, Urban, 1951-, et al.
(författare)
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Impact of Selenium on Biomarkers and Clinical Aspects Related to Ageing : A Review
- 2021
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Ingår i: Biomolecules. - : MDPI. - 2218-273X. ; 11:10
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Tidskriftsartikel (refereegranskat)abstract
- Selenium (Se) is an essential dietary trace element that plays an important role in the prevention of inflammation, cardiovascular diseases, infections, and cancer. Selenoproteins contain selenocysteine in the active center and include, i.a., the enzymes thioredoxin reductases (TXNRD1-3), glutathione peroxidases (GPX1-4 and GPX6) and methionine sulfoxide reductase, involved in immune functions, metabolic homeostasis, and antioxidant defense. Ageing is an inevitable process, which, i.a., involves an imbalance between antioxidative defense and reactive oxygen species (ROS), changes in protein and mitochondrial renewal, telomere attrition, cellular senescence, epigenetic alterations, and stem cell exhaustion. These conditions are associated with mild to moderate inflammation, which always accompanies the process of ageing and age-related diseases. In older individuals, Se, by being a component in protective enzymes, operates by decreasing ROS-mediated inflammation, removing misfolded proteins, decreasing DNA damage, and promoting telomere length. Se-dependent GPX1-4 and TXNRD1-3 directly suppress oxidative stress. Selenoprotein H in the cell nucleus protects DNA, and selenoproteins residing in the endoplasmic reticulum (ER) assist in the removal of misfolded proteins and protection against ER stress. In this review, we highlight the role of adequate Se status for human ageing and prevention of age-related diseases, and further its proposed role in preservation of telomere length in middle-aged and elderly individuals.
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| 8. |
- Alehagen, Urban, 1951-, et al.
(författare)
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Improved cardiovascular health by supplementation with selenium and coenzyme Q10 : applying structural equation modelling (SEM) to clinical outcomes and biomarkers to explore underlying mechanisms in a prospective randomized double-blind placebo-controlled intervention project in Sweden
- 2022
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Ingår i: European Journal of Nutrition. - : Springer Heidelberg. - 1436-6207 .- 1436-6215. ; 61:6, s. 3135-3148
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Selenium and coenzyme Q10 have synergistic antioxidant functions. In a four-year supplemental trial in elderly Swedes with a low selenium status, we found improved cardiac function, less cardiac wall tension and reduced cardiovascular mortality up to 12 years of follow-up. Here we briefly review the main results, including those from studies on biomarkers related to cardiovascular risk that were subsequently conducted. In an effort, to explain underlying mechanisms, we conducted a structured analysis of the inter-relationship between biomarkers. Methods Selenium yeast (200 mu g/day) and coenzyme Q10 (200 mg/ day), or placebo was given to 443 elderly community-living persons, for 48 months. Structural Equation Modelling (SEM) was used to investigate the statistical inter-relationships between biomarkers related to inflammation, oxidative stress, insulin-like growth factor 1, expression of microRNA, fibrosis, and endothelial dysfunction and their impact on the clinical effects. The main study was registered at Clinicaltrials.gov at 30th of September 2011, and has the identifier NCT01443780. Results In addition to positive clinical effects, the intervention with selenium and coenzyme Q10 was also associated with favourable effects on biomarkers of cardiovascular risk. Using these results in the SEM model, we showed that the weights of the first-order factors inflammation and oxidative stress were high, together forming a second-order factor inflammation/oxidative stress influencing the factors, fibrosis (beta = 0.74; p < 0.001) and myocardium (beta = 0.65; p < 0.001). According to the model, the intervention impacted fibrosis and myocardium through these factors, resulting in improved cardiac function and reduced CV mortality. Conclusion Selenium reduced inflammation and oxidative stress. According to the SEM analysis, these effects reduced fibrosis and improved myocardial function pointing to the importance of supplementation in those low on selenium and coenzyme Q10.
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| 9. |
- Alehagen, Urban, 1951-, et al.
(författare)
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Increased mortality in the A/A genotype of the SNP rs28372698 of interleukin 32
- 2021
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Ingår i: Experimental and Therapeutic Medicine. - : SPANDIDOS PUBL LTD. - 1792-0981 .- 1792-1015. ; 21:2
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Tidskriftsartikel (refereegranskat)abstract
- One of the major causes of mortality in the western hemisphere is cardiovascular disease. Therefore, a variety of markers to identify those at risk are required. Interleukin-32 (IL-32) is a cytokine that is associated with inflammation. The aim of the current study was to investigate variations in single nucleotide polymorphisms (SNPs) of IL-32 and plasma expression, and their associations with mortality. A population of 486 elderly community-living persons were evaluated. The participants were followed for 7.1 years and underwent a clinical examination and blood sampling. SNP analyses of IL-32 rs28372698 using allelic discrimination and plasma measurement of IL-32, using ELISA, were performed. During the follow-up period, 140 (28.8%) all-cause and 87 (17.9%) cardiovascular deaths were registered. No significant difference between mortality and plasma concentration of IL-32 was observed. The A/A genotype group exhibited significantly higher all-cause mortality (P=0.036), and an almost two-fold increased risk in a multivariate Cox regression model for all-cause and cardiovascular mortality. A highly significant difference in all-cause and cardiovascular mortality between the A/A and the T/T groups was demonstrated (P=0.015 resp. P=0.014). In the present study, the cytokine IL-32 was demonstrated to have prognostic information, with an increased risk of all-cause and cardiovascular mortality for those with the A/A genotype rs28372698 of IL-32. The A/A genotype could therefore be regarded as a possible biomarker for mortality risk that may be used to offer optimized cardiovascular patient handling in the future. However, the present study sample was small, and the results should be regarded as hypothesis-generating.
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| 10. |
- Alehagen, Urban, 1951-, et al.
(författare)
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Reference intervals and decision limits for B-type natriuretic peptide (BNP) and its precursor (Nt-proBNP) in the elderly
- 2007
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Ingår i: Clinica Chimica Acta. - : Elsevier BV. - 0009-8981 .- 1873-3492. ; 382:1-2
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Tidskriftsartikel (refereegranskat)abstract
- Background: Elderly patients have the highest prevalence of heart failure (HF). The aims of the study were to establish a reference interval for B-type natriuretic peptide (BNP) and (Nt-proBNP) in elderly people, and to identify clinically relevant decision limits based on long-term outcome. Methods: Plasma concentrations of BNP and Nt-proBNP were measured from two elderly populations: 218 healthy subjects (mean age 73 years, population I), and 474 patients (mean age 73 years, population II) with symptoms associated with HF. Study population II was followed for 6 years with registration of all cardiovascular mortality. Results: An association between both BNP and Nt-proBNP concentrations and age was found. The upper limit for the reference intervals in the healthy elderly (population I) was: BNP ≤ 28 pmol/L (≤ 97 ng/L), and Nt-proBNP ≤ 64 pmol/L (≤ 540 ng/L). Based on cardiovascular mortality, decision limits for BNP (∼ 50 pmol/L, ∼ 170 ng/L) and Nt-proBNP (∼ 200 pmol/L, ∼ 1700 ng/L) (population II) were determined. Conclusions: Besides establishing reference intervals for BNP and Nt-proBNP in an elderly population, a higher clinically relevant decision limit for BNP and Nt-proBNP was identified, indicating additive prognostic information of the peptides on top of measurements by echocardiography. Therefore, both reference intervals and decision limits should be included in clinical practice. © 2007.
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