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  • Al-Majdoub, M., et al. (författare)
  • Population-level analysis to determine parameters that drive variation in the plasma metabolite profiles
  • 2018
  • Ingår i: Metabolites. - : Multidisciplinary Digital Publishing Institute. - 2218-1989. ; 8:4
  • 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.
  • Bennet, Louise, et al. (författare)
  • Diastolic dysfunction is associated with sedentary leisure time physical activity and smoking in females only
  • 2010
  • Ingår i: SCANDINAVIAN JOURNAL OF PRIMARY HEALTH CARE. - : Taylor & Francis. - 0281-3432. ; 28:3, s. 172-178
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives. Left ventricular diastolic dysfunction with preserved systolic function (DD-PSF) is associated with an increased risk of morbidity and mortality. Population-based surveys studying the associations between DD-PSF and lifestyle-associated risk factors, such as leisure time physical activity (LTPA) and smoking, are scarce. Thus, the aims were to explore the associations between DD-PSF and LTPA and smoking, employing optimal echocardiographic techniques. Design. Cross-sectional study conducted from 2001 to 2003. Setting.The study was conducted in a random sample of a rural Swedish population. Subjects. Men and women of 30–75 years of age were consecutively invited for conventional echocardiography and tissue velocity imaging (n = 1149). Structured questionnaires and physical examinations were conducted using standardized methods. Main outcome measures. DD-PSF was defined according to the European Society of Cardiology criteria excluding subjects with ejection fraction < 45%, or a self-reported history of heart failure. Results. Complete information was available in 500 men and 538 women. In a multivariate model, DD-PSF was independently associated with sedentary LTPA and smoking in females; sedentary LTPA odds ratio (OR) 2.91, 95% confidence interval (CI) 1.02 to 8.27, and smoking OR 3.42, 95% CI 1.35 to 8.64. The probability of identifying DD-PSF in females with a sedentary LTPA was 37% and increased to 80% if they also had hypertension and were obese. Conclusions. Sedentary LTPA and smoking are independently associated with DD-PSF in females. Identification of a sedentary lifestyle in females increases the probability of diagnosing DD-PSF.
  • Buschard, Karsten, et al. (författare)
  • Low serum concentration of sulfatide and presence of sulfated lactosylceramid are associated with Type 2 diabetes. The Skaraborg Project
  • 2005
  • Ingår i: Diabetic Medicine. - : Wiley-Blackwell. - 0742-3071 .- 1464-5491. ; 22:9, s. 1190-8
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS: The glycosphingolipid sulfatide (sulfated galactosyl-ceramide) increases exocytosis of beta-cell secretory granules, activates K(ATP)-channels and is thereby able to influence insulin secretion through its presence in the islets. A closely related compound, sulfated lactosylceramide (sulf-lac-cer), is present in the islets during fetal and neonatal life when, as in Type 2 diabetes, insulin is secreted autonomically without the usual first phase response to glucose. The aim was to examine whether serum concentrations of these glycolipids are associated with Type 2 diabetes. METHODS: A case-control study, comprising 286 women and 283 men, was designed using a population-based sample of patients with Type 2 diabetes and a population survey. RESULTS: Low serum concentrations of sulfatide were associated with Type 2 diabetes, independent of traditional risk factors for diabetes in a sex-specific analysis: odds ratio (OR) 2.1 (95% confidence interval 1.1, 3.9) in men, and 2.3 (1.2, 4.3) in women, comparing the lowest and the highest tertiles. Type 2 diabetes was also associated with detectable amounts of sulf-lac-cer in serum: OR 1.7 (0.9, 3.4) in men, and 7.6 (3.8, 15.2) in women. After adjustment for confounding from other diabetes risk factors, these associations remained basically unchanged. The connections between sulfatide and Type 2 diabetes, and sulf-lac-cer and Type 2 diabetes were independent of each other. Insulin resistance (HOMA-IR) was negatively correlated with sulfatide concentration and positively correlated with sulf-lac-cer (both P < 0.0001, independently). CONCLUSIONS: We report a new, robust and highly significant independent association between Type 2 diabetes and serum concentrations of sulfatide in both sexes, and sulf-lac-cer in females. The associations were also independent of other known diabetes risk factors.
  • Carrera-Bastos, Pedro, et al. (författare)
  • C-reactive protein in traditional melanesians on Kitava
  • 2020
  • Ingår i: BMC Cardiovascular Disorders. - : BioMed Central (BMC). - 1471-2261. ; 20:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Population-based levels of the chronic low-grade systemic inflammation biomarker, C-reactive protein (CRP), vary widely among traditional populations, despite their apparent absence of chronic conditions associated with chronic low-grade systemic inflammation, such as type 2 diabetes, metabolic syndrome and cardiovascular disease. We have previously reported an apparent absence of aforementioned conditions amongst the traditional Melanesian horticulturalists of Kitava, Trobriand Islands, Papua New Guinea. Our objective in this study was to clarify associations between chronic low-grade systemic inflammation and chronic cardiometabolic conditions by measuring CRP in a Kitava population sample. For comparison purposes, CRP was also measured in Swedish controls matched for age and gender. Methods: Fasting levels of serum CRP were measured cross-sectionally in ≥ 40-year-old Kitavans (N = 79) and Swedish controls (N = 83). Results: CRP was lower for Kitavans compared to Swedish controls (Mdn 0.5 mg/L range 0.1—48 mg/L and Mdn 1.1 mg/L range 0.1—33 mg/L, respectively, r =.18 p =.02). Among Kitavans, there were small negative associations between lnCRP for CRP values < 10 and total, low-density lipoprotein (LDL) and non-high-density lipoprotein (non-HDL) cholesterol. Among Swedish controls, associations of lnCRP for CRP values < 10 were medium positive with weight, body mass index, waist circumference, hip circumference and waist-hip ratio and low positive with triglyceride, total cholesterol-HDL cholesterol ratio, triglyceride-HDL cholesterol ratio and serum insulin. Conclusions: Chronic low-grade systemic inflammation, measured as CRP, was lower among Kitavans compared to Swedish controls, indicating a lower and average cardiovascular risk, respectively, for these populations.
  • Ingelsson, Erik, et al. (författare)
  • The PPARGC1A Gly482Ser polymorphism is associated with left ventricular diastolic dysfunction in men.
  • 2008
  • Ingår i: BMC cardiovascular disorders. - : BioMed Central (BMC). - 1471-2261. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The Gly482Ser polymorphism in peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PPARGC1A) has been demonstrated to be associated with diabetes, obesity and hypertension, all of which are important risk factors for left ventricular diastolic dysfunction. METHODS: The PPARGC1A Gly482Ser polymorphism was genotyped in a community-based cohort of 499 men and 533 women, who also underwent an echocardiographic examination to determine their left ventricular diastolic function. The association between the polymorphism and the presence of diastolic dysfunction was evaluated using logistic regression models. RESULTS: The Ser allele of the PPARGC1A Gly482Ser polymorphism was significantly associated with a lower risk of diastolic dysfunction in men, but not in women. In a model adjusting for potential confounders (age, body mass index, leisure time physical activity, hypertension and diabetes) the results were still significant and substantial (odds ratio 0.13, 95% confidence interval 0.03-0.54, p for trend = 0.004). The results were consistent in a series of models, and they imply a multiplicative, protective effect of the Ser allele, with lower risk of diastolic dysfunction for each copy of the allele. CONCLUSION: The Ser allele of the PPARGC1A Gly482Ser polymorphism was associated with decreased risk of diastolic left ventricular dysfunction in men, but not in women, in our large community-based sample. It was associated with a substantially decreased risk, even after adjustment for potential confounders. The clinical importance of the findings has to be established in further studies.
  • Littorin, Bengt, et al. (författare)
  • Increasing body mass index at diagnosis of diabetes in young adult people during 1983-1999 in the Diabetes Incidence Study in Sweden (DISS).
  • 2003
  • Ingår i: Journal of Internal Medicine. - : Wiley-Blackwell. - 1365-2796 .- 0954-6820. ; 254:3, s. 251-256
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. To study trends in body mass index (BMI) at diagnosis of diabetes in all young Swedish adults in the age range of 15-34 years registered in a nation-based registry. Design. The BMI was assessed at diagnosis in diabetic patients 15-34 years of age at diagnosis, for a period of 17 years (1983-1999). Islet cell antibodies (ICA) were measured during three periods (1987-1988, 1992-1993 and 1998-1999). Setting. A nationwide study (Diabetes Incidence Study in Sweden). Subjects. A total of 4727 type 1 and 1083 type 2 diabetic patients. Main outcome measures. Incidence-year specific BMI adjusted for age, gender and time of diagnosis (month). Results. Body mass index at diagnosis increased significantly both in type 1 (21.4 ± 3.6 to 22.5 ± 4.0; P < 0.0001) and in type 2 (27.4 ± 6.8 to 32.0 ± 6.0; P < 0.0001) diabetic patients, also when adjusted for age, gender and month of diagnosis. A similar significant increase in BMI was found in type 1 diabetic patients and in type 2 diabetic patients in the periods 1987-1988, 1992-1993 and 1998-1999; years when ICA were assessed and considered in the classification of diabetes. Despite this increase in BMI, there was no increase in the incidence of diabetes in young-adult people in Sweden. Conclusion. Body mass index at diagnosis of diabetes in subjects 15-34 years of age has substantially increased during 1983-1999 in Sweden when adjusted for age, gender and month of diagnosis.
  • Melander, Olle, et al. (författare)
  • Association between a variant in the 11 beta-hydroxysteroid dehydrogenase type 2 gene and primary hypertension
  • 2000
  • Ingår i: Journal of Human Hypertension. - : Nature Publishing Group. - 1476-5527. ; 14:12, s. 819-823
  • Tidskriftsartikel (refereegranskat)abstract
    • The enzyme 11 beta-hydroxysteroid dehydrogenase type 2 (11BHSD2) converts cortisol to cortisone in the kidney, thereby protecting the mineralocorticoid receptor from the mineralocorticoid actions of cortisol. The syndrome of Apparent Mineralocorticoid Excess (AME), a rare monogenic form of early onset hypertension with autosomal recessive inheritance, is caused by homozygous or compound heterozygous loss of function mutations in the 11BHSD2 gene. Association has been reported between a microsatellite marker flanking the 11BHSD2 gene (D16S496) and primary hypertension. The aim of this study was to identify variants in the 11BHSD2 gene and to test if such variants or the D16S496 are associated with primary hypertension, in Swedes. To address this, the coding sequences of the 11BHSD2 gene was screened for mutations in 20 patients with primary hypertension with single strand conformation polymorphism and direct DNA sequencing techniques. A polymorphism was identified in exon 3; G534A (Glu178Glu). This polymorphism and the D16S496 microsatellite were tested for association with primary hypertension in a population consisting of 292 patients with primary hypertension and 263 normotensive control subjects. The frequency of G534G homozygotes was higher in patients with primary hypertension than in normotensive control subjects (92.8% vs 87.8%; P < 0.05). The allele frequencies of the D16S496 microsatellite did not differ between the two groups (chi(2) = 11.0, df = 10; P = 0.36). In conclusion, over-representation of individuals homozygous for the G534 allele in hypertensive patients compared with control subjects suggests that a mutation in linkage disequilibrium with the G534A polymorphism could increase susceptibility to primary hypertension. Journal of Human Hypertension (2000) 14, 819-823
  • Melander, Olle, et al. (författare)
  • Genetic variants of thiazide-sensitive NaCl-cotransporter in Gitelman's syndrome and primary hypertension
  • 2000
  • Ingår i: Hypertension. - : Lippincott Williams & Wilkins. - 1524-4563. ; 36:3, s. 389-394
  • Tidskriftsartikel (refereegranskat)abstract
    • Gitelman's syndrome is an autosomal recessive disorder characterized by electrolyte disturbances and low blood pressure. The disease is caused by homozygous or compound heterozygous inactivating mutations in the thiazide-sensitive NaCl-cotransporter gene leading to reduced renal sodium reabsorption. We report 4 patients with Gitelman's syndrome from southern Sweden, all in whom we identified compound heterozygous mutations in the thiazide-sensitive NaCl-cotransporter gene (Gly439Ser, Gly731Arg, Gly741Arg, Thr304Pro, and 2745insAGCA), of which the latter 2 have not been described before. We hypothesized that such mutations in their heterozygous form protect against primary hypertension in the general population and that the gene may also harbor activating mutations that increase the risk for primary hypertension. Accordingly, the gene was screened for mutations in 20 patients with primary hypertension and in 20 normotensive subjects by single-strand conformation polymorphism and direct DNA sequencing. The Arg904Gln, Gly264Ala, and C1420T variants, found in the mutation screening of subjects without Gitelman's syndrome, were studied further. Population genotype frequencies were determined in 292 unrelated patients with primary hypertension and 264 unrelated normotensive subjects from southern Sweden. Gln904 homozygotes were overrepresented in hypertensive patients compared with normotensive subjects (5 of 292 versus 0 of 264; P:=0.03). In conclusion, we confirm that Gitelman's syndrome is caused by mutations in the thiazide-sensitive NaCl-cotransporter gene. Our results further suggest that subjects homozygous for the Gln904 variant have an increased risk for development of primary hypertension.
  • Melander, Olle, et al. (författare)
  • Role of the Gly460Trp polymorphism of the alpha-adducin gene in primary hypertension in Scandinavians
  • 2000
  • Ingår i: Journal of Human Hypertension. - : Nature Publishing Group. - 1476-5527. ; 14:1, s. 43-46
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous studies have suggested that the Trp460 allele of the Gly460Trp polymorphism in the alpha-adducin gene is associated with salt sensitivity and primary hypertension. The present study was undertaken to evaluate if the Trp460 allele of this polymorphism is associated with primary hypertension in Scandinavians. To address this issue, 294 patients with primary hypertension and 265 normotensive control subjects from Sweden were examined and genotyped for the Gly460Trp polymorphism using polymerase chain reaction and restriction fragment length polymorphism methods. We then used a population of 80 patients with primary hypertension and 154 normotensive control subjects from Finland to replicate the findings. The frequency of the Trp460 allele was lower in hypertensive patients than in normotensive controls in the Swedish population (17.7% vs 23.0%; P = 0.03) and in the Finnish population (14.4% vs 19.5%; NS). Therefore we also performed a pooled analysis in which the frequency of the Trp460 allele was significantly lower in hypertensive patients than in normotensive controls (17.0% vs 21. 7%; P = 0.02). In subjects who did not receive antihypertensive medication (n = 447) there was no difference between carriers of the three different codon 460 genotypes (Trp-Trp; Trp-Gly and Gly-Gly) either for systolic (128 +/- 18; 127 +/- 15 and 129 +/- 17 mm Hg, NS) or for diastolic blood pressure (75.6 +/- 12.1; 74.7 +/- 9.3 and 75.0 +/- 10.4 mm Hg, NS). In conclusion, the lower frequency of the Trp460 allele in hypertensive patients than in normotensive controls strongly argues against a pathogenic role of this allele in primary hypertension. The results rather suggest that another variant in linkage disequilibrium with the Gly460Trp polymorphism increases susceptibility for hypertension.Journal of Human Hypertension (2000) 14, 43-46.
  • Nyholm, Maria, et al. (författare)
  • The validity of obesity based on self-reported weight and height: Implications for population studies
  • 2007
  • Ingår i: Obesity. - Hoboken : Wiley-Blackwell. ; 15:1, s. 197-208
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To validate self-reported information on weight and height in an adult population and to find a useful algorithm to assess the prevalence of obesity based on self-reported information. RESEARCH METHODS AND PROCEDURES: This was a cross-sectional survey consisting of 1703 participants (860 men and 843 women, 30 to 75 years old) conducted in the community of Vara, Sweden, from 2001 to 2003. Self-reported weight, height, and corresponding BMI were compared with measured data. Obesity was defined as measured BMI > or = 30 kg/m2. Information on education, self-rated health, smoking habits, and physical activity during leisure time was collected by a self-administered questionnaire. RESULTS: Mean differences between measured and self-reported weight were 1.6 kg (95% confidence interval, 1.4; 1.8) in men and 1.8 kg (1.6; 2.0) in women (measured higher), whereas corresponding differences in height were -0.3 cm (-0.5; -0.2) in men and -0.4 cm (-0.5; -0.2) in women (measured lower). Age and body size were important factors for misreporting height, weight, and BMI in both men and women. Obesity (measured) was found in 156 men (19%) and 184 women (25%) and with self-reported data in 114 men (14%) and 153 women (20%). For self-reported data, the sensitivity of obesity was 70% in men and 82% in women, and when adjusted for corrected self-reported data and age, it increased to 81% and 90%, whereas the specificity decreased from 99% in both sexes to 97% in men and 98% in women. DISCUSSION: The prevalence of obesity based on self-reported BMI can be estimated more accurately when using an algorithm adjusted for variables that are predictive for misreporting.
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