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  • 1.
    Branth, Stefan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Ronquist, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Stridsberg, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Hambraeus, Leif
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Kindgren, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Olsson, Roger
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Carlander, David
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Arnetz, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Socialmedicin.
    Development of abdominal fat and incipient metabolic syndrome in young healthy men exposed to long-term stress2007Inngår i: NMCD. Nutrition Metabolism and Cardiovascular Diseases, ISSN 0939-4753, E-ISSN 1590-3729, Vol. 17, nr 6, s. 427-435Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND AND AIM: The sympathetic nervous system may be involved in the pathophysiology of insulin resistance and metabolic cardiovascular syndrome in young men. The aim was to study the effects of long-term stress on different features of the metabolic syndrome (MES) in formerly non-obese healthy young males during 5 months of defined conditions. METHODS AND RESULTS: Sixteen healthy male sailors (mean age 36.5 (SD)+/-7 years) participating in a sailing race around the world were recruited for the study. Investigations were done before the start and at stop overs after finishing laps 1, 2 and 4 (1, 2(1/2) and 5 months, respectively). Anthropometric and blood pressure data as well as biochemical data associated with MES were substantiated. Food intake and exercise were chartered and largely controlled. A mean weight loss of 4.5+/-2 kg (P<0.005), comprising both fat and lean body mass, was recorded during the first lap. Subsequently after 5 months, a weight gain, mainly consisting of 1.2+/-1.1 kg body fat (P<0.05), took place, concomitantly with a protein mass drop of 0.6+/-1.1 kg (P<0.05). The body fat gain accumulated on the abdominal region. Elevated blood levels of HbA1c, insulin and the triglycerides/high-density lipoprotein ratio were also observed during the race. Likewise heart rate and systolic blood pressure increased slightly but to a statistically significant extent. CONCLUSIONS: Non-obese healthy young men exposed to long-term stress developed abdominal obesity and signs of a metabolic syndrome in embryo, also emphasized by biochemical and blood pressure alterations. It is suggested that long-term and sustained stress activation might be an additional risk factor for the development of MES, even after control of dietary and exercise habits.

  • 2. Carlsson, A. C.
    et al.
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Ärnlov, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Borne, Y.
    Leander, K.
    Gigante, B.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Hellenius, M. -L
    Bottai, M.
    de Faire, U.
    Prediction of cardiovascular disease by abdominal obesity measures is dependent on body weight and sex - Results from two community based cohort studies2014Inngår i: NMCD. Nutrition Metabolism and Cardiovascular Diseases, ISSN 0939-4753, E-ISSN 1590-3729, Vol. 24, nr 8, s. 891-899Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aim: To study waist-hip ratio (WHR), waist circumference (WC), sagittal abdominal diameter (SAD), and waist-hip-height ratio (WHHR) as predictors of CVD, in men and women stratified by BMI (cut-off >= 25). Methods and results: A cohort of n = 3741 (53% women) 60-year old individuals without CVD was followed for 11-years (375 CVD cases). To replicate the results, we also assessed another large independent cohort; The Malmo Diet and Cancer study - cardiovascular cohort (MDCC, (n = 5180, 60% women, 602 CVD cases during 16-years). After adjustment for established risk factors in normal-weight women, the hazard ratio (HR) per one standard deviation (SD) were; WHR; 1.91 (95% confidence interval (CI) 1.35-2.70), WC; 1.81 (95% CI 1.02-3.20), SAD; 1.25 (95% CI 0.74-2.11), and WHHR; 1.97 (95% CI 1.40-2.78). In men the association with WHR, WHHR and WC were not significant, whereas SAD was the only measure that significantly predicted CVD in men (HR 1.19 (95% CI 1.04-1.35). After adjustments for established risk factors in overweight/obese women, none of the measures were significantly associated with CVD risk. In men, however, all measures were significant predictors; WHR; 1.24 (955 CI 1.04-1.47), WC 1.19 (95% CI 1.00-1.42), SAD 1.21 (95% CI 1.00-1.46), and WHHR; 1.23 (95% CI 1.05-1.44). Only the findings in men with BMI >= 25 were verified in MDCC. Conclusion: In normal weight individuals, WHHR and WHR were the best predictors in women, whereas SAD was the only independent predictor in men. Among overweight/obese individuals all measures failed to predict CVD in women, whereas WHHR was the strongest predictor after adjustments for CVD risk factors in men.

  • 3.
    Daryani, Achraf
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap. Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Institutionen för hushållsvetenskap (IHV).
    Basu, Samar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Becker, Wulf
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Antioxidant intake, oxidative stress and inflammation among immigrant women from the Middle East living in Sweden: associations with cardiovascular risk factors2007Inngår i: NMCD. Nutrition Metabolism and Cardiovascular Diseases, ISSN 0939-4753, E-ISSN 1590-3729, Vol. 17, nr 10, s. 748-756Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background and aims: Immigrant women from the Middle East have higher cardiovascular risk compared to native women. Whether low antioxidant intake, oxidative stress or inflammation contributes to risk is unknown. In a cross-sectional study of 157 randomly selected foreign-born women (Iranian and Turkish) and native women living in Sweden, we investigated antioxidant status, oxidative stress (F-2-isoprostanes) and systemic inflammation (plasma high sensitive C-reactive protein; CRP) markers. We also investigated relationships between F2-isoprostanes, CRP and cardiovascular risk factors. Methods and result: Dietary intake was assessed using 24-h dietary recalls repeated four times. Micronutrient intake was not consistently different between groups. Serum a-tocopherol, but not gamma-tocopherot levels, was tower in Turkish vs. Swedish women (P < 0.05). Turkish women had the highest F-2-isoprostane levels (P < 0.05 vs. Iranian women) and CRP levels (P < 0.01 vs. Swedish women and P = 0.05 vs. Iranian women). In immigrants (n = 97), F-2-isoprostanes correlated positively to insulin levels (r = 0.31, P < 0.01), and CRP was correlated to obesity and several cardiovascular risk factors (r-values >0.21, P values <0.05). Conclusion: The rote of antioxidant status is unclear, whereas signs of oxidative stress and inflammation are evident in immigrant women from Middle East, especially Turkish women. Oxidative stress and low-grade inflammation might contribute to the higher cardiovascular risk previously observed in immigrant women. Further larger studies adjusting for more potential confounders are motivated to confirm these results.

  • 4. Delgado-Lista, J.
    et al.
    Perez-Martinez, P.
    Garcia-Rios, A.
    Phillips, C. M.
    Hall, W.
    Gjelstad, I. M. F.
    Lairon, D.
    Saris, W.
    Kiec-Wilk, B.
    Karlström, Brita
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Drevon, C. A.
    Defoort, C.
    Blaak, E. E.
    Dembinska-Kiec, A.
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Lovegrove, J. A.
    Roche, H. M.
    Lopez-Miranda, J.
    A gene variation (rs12691) in the CCAT/enhancer binding protein alpha modulates glucose metabolism in metabolic syndrome2013Inngår i: NMCD. Nutrition Metabolism and Cardiovascular Diseases, ISSN 0939-4753, E-ISSN 1590-3729, Vol. 23, nr 5, s. 417-423Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background and aims: CCAAT/enhancer-binding protein alpha (CEBPA) is a transcription factor involved in adipogenesis and energy homeostasis. Caloric restriction reduces CEBPA protein expression in patients with metabolic syndrome (MetS). A previous report linked rs12691 SNP in CEBPA to altered concentration of fasting triglycerides. Our objective was to assess the effects of rs12691 in glucose metabolism in Metabolic Syndrome (MetS) patients. Methods and results: Glucose metabolism was assessed by static (glucose, insulin, adiponectin, leptin and resistin plasma concentrations) and dynamic (disposition index, insulin sensitivity index, HOMA-IR and acute insulin response to glucose) indices, performed at baseline and after 12 weeks of 4 dietary interventions (high saturated fatty acid (SFA), high monounsaturated fatty acid (MUFA), low-fat and low-fat-high-n3 polyunsaturated fatty acid (PUFA)) in 486 subjects with MetS. Carriers of the minor A allele of rs12691 had altered disposition index (p = 0.0003), lower acute insulin response (p = 0.005) and a lower insulin sensitivity index (p = 0.025) indicating a lower insulin sensitivity and a lower insulin secretion, at baseline and at the end of the diets. Furthermore, A allele carriers displayed lower HDL concentration. Conclusion: The presence of the A allele of rs12691 influences glucose metabolism of MetS patients. Clinical Trials Registry number NCT00429195.

  • 5. Giacco, R.
    et al.
    Cuomo, V,
    Vessby, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Uusitupa, M.
    Hermansen, K.
    Meyer, B.J.
    Riccardi, G.
    Rivellese, A.A.
    Fish oil, insulin sensitivity, insulin secretion and glucose tolerance in healthy people: Is there any effect of fish oil supplementation in relation to the type of background diet and habitual dietary intake of n-6 and n-3 fatty acids?2007Inngår i: NMCD. Nutrition Metabolism and Cardiovascular Diseases, ISSN 0939-4753, E-ISSN 1590-3729, Vol. 17, nr 8, s. 572-580Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aim

    To evaluate whether a moderate supplementation of long-chain n-3 fatty acids is able to modulate insulin sensitivity, insulin secretion, β-cell function and glucose tolerance in healthy individuals consuming a diet rich in either saturated or monounsaturated fat, also in relation to their habitual dietary intake of n-6 and n-3 fatty acid.

    Methods and results

    One hundred and sixty-two healthy individuals were randomly assigned to follow either one of two isoenergetic diets for 3months, one rich in monounsaturated fats and the other rich in saturated fats. Within each group there was a second randomisation to fish oil (n-3 fatty acids 3.6g/day) or placebo. At the beginning and at the end of the treatment periods insulin sensitivity (SI), first phase insulin response (FPIR) and glucose tolerance (KG-value) were evaluated by the intravenous glucose tolerance test (IVGTT).

    Fish oil did not have any effect on SI, FPIR, KG-value and disposition index in either diet. Even after dividing subjects according to the median value of n-6/n-3 ratio of serum phospholipids at baseline, there was no change in SI (Δ SI 0.42±0.34 on fish oil vs 0.14±0.23 on placebo for those with n-6/n-3 <4.85; −1.03±0.47 on fish oil vs −0.27±0.32 on placebo for those with n-6/n-3 >4.85) (M±SE), FPIR (Δ FPIR 135.9±78.9 vs 157.2±157.5pmol/L; 38.8±181.7 vs 357.1±181.7pmol/L), KG-value (Δ KG 0.14±0.15 vs 0.12±0.11; −0.32±0.16 vs 0.15±0.15) or disposition index (Δ disposition index 1465.4±830.4 vs 953.8±690.0; −1641.6±1034.3 vs 446.6±905.1). Considering the 75th percentile of n-6/n-3 ratio (5.82) the results on insulin sensitivity, insulin secretion and disposition index were confirmed, while, in this more extreme situation, n-3 fatty acid supplementation induced a significant deterioration of KG-value (p=0.02).

    Conclusions

    In healthy individuals a moderate supplementation of fish oil does not affect insulin sensitivity, insulin secretion, β-cell function or glucose tolerance. The same is true even when the habitual dietary intake of n-6 and n-3 fatty acids is taken into account.

  • 6. Helal, O.
    et al.
    Defoort, C.
    Robert, S.
    Marin, C.
    Lesavre, N.
    Lopez-Miranda, J.
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Basu, Samur
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Oxidativ stress och inflammation.
    Lovegrove, J.
    McMonagle, J.
    Roche, H. M.
    Dignat-George, F.
    Lairon, D.
    Increased levels of microparticles originating from endothelial cells, platelets and erythrocytes in subjects with metabolic syndrome: Relationship with oxidative stress2011Inngår i: NMCD. Nutrition Metabolism and Cardiovascular Diseases, ISSN 0939-4753, E-ISSN 1590-3729, Vol. 21, nr 9, s. 665-671Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background and aims: The Metabolic Syndrome (MetS) is associated with increased cardiovascular risk. Circulating microparticles (MP) are involved in the pathogenesis of atherothrombotic disorders and are raised in individual with CVD. We measured their level and cellular origin in subjects with MetS and analyzed their associations with 1/anthropometric and biological parameters of MetS, 2/inflammation and oxidative stress markers.

    Methods and results: Eighty-eight subjects with the MetS according to the NCEP-ATPIII definition were enrolled in a bicentric study and compared to 27 healthy controls. AnnexinV-positive MP (TMP), MP derived from platelets (PMP), erythrocytes (ErMP), endothelial cells (EMP), leukocytes (LMP) and granulocytes (PNMP) were determined by flow cytometry. MetS subjects had significantly higher counts/mu l of TMP (730.6 +/- 49.7 vs 352.8 +/- 35.6), PMP (416.0 +/- 43.8 vs 250.5 +/- 23.5), ErMP (243.8 +/- 22.1 vs 73.6 +/- 19.6) and EMP (7.8 +/- 0.8 vs 4.0 +/- 1.0) compared with controls. LMP and PNMP were not statistically different between groups. Multivariate analysis demonstrated that each criterion for the MetS influenced the number of TMP. Waist girth was a significant determinant of PMP and EMP level and blood pressure was correlated with EMP level. Glycemia positively correlated with PMP level whereas dyslipidemia influenced EMP and ErMP levels. Interestingly, the oxidative stress markers, plasma glutathione peroxy-dase and urinary 8-iso-prostaglandin F(2) alpha, independently influenced TMP and PMP levels whereas inflammatory markers did not, irrespective of MP type.

    Conclusion: Increased levels of TMP, PMP, ErMP and EMP are associated with individual metabolic abnormalities of MetS and oxidative stress. Whether MP assessment may represent a marker for risk stratification or a target for pharmacological intervention deserves further investigation.

  • 7. Krachler, Benno
    et al.
    Norberg, Margareta
    Eriksson, Jan W
    Hallmans, Göran
    Johansson, Ingegerd
    Vessby, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Weinehall, Lars
    Lindahl, Bernt
    Fatty acid profile of the erythrocyte membrane preceding development of Type 2 diabetes mellitus2008Inngår i: NMCD. Nutrition Metabolism and Cardiovascular Diseases, ISSN 0939-4753, E-ISSN 1590-3729, Vol. 18, nr 7, s. 503-10Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background and aims: The respective roles of dietary fatty acids in the pathogenesis of diabetes are as yet unclear. Erythrocyte membrane fatty acid (EMFA) composition may provide an estimate of dietary fatty acid intake. This study investigates the relation between EMFA composition and development of Type 2 diabetes mellitus.Methods and results: In a nested case-referent design we studied 159 individuals tested as non-diabetic at baseline who after a mean observation time of 5.4 +/- 2.6 years were diagnosed with Type 2 diabetes mellitus and 291 sex- and age-matched referents. Higher proportions of pentadecanoic acid (15: 0) and heptadecanoic acid (17:0) were associated with a tower risk of diabetes. In accordance with earlier findings, higher proportions of palmitoleic (16:1 n-7), dihomo-gamma-linotenic (20:3 n-6) and adrenic (22:4 n-6) acids were associated with increased risk, whereas linoleic (18:2 n-6) and clupanodonic (22:5 n-3) acids were inversely associated with diabetes. After adjustment for BMI, HbA1c, alcohol intake, smoking and physical activity the only significant predictors were 15:0 and 17:0 as protective factors and 22:4 n6 as risk factor.Conclusion: In accordance with previous studies, our results indicate that EMFA-patterns predict development of Type 2 diabetes mellitus. The inverse association with two saturated fatty acids, previously shown to reflect consumption of dairy products, is a new finding.

  • 8.
    Larsson, S. C.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi. Karolinska Inst, Inst Environm Med, Unit Nutr Epidemiol, SE-17177 Stockholm, Sweden.
    Wolk, Alicja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi. Karolinska Inst, Inst Environm Med, Unit Nutr Epidemiol, SE-17177 Stockholm, Sweden;Uppsala Univ, Dept Surg Sci, Uppsala, Sweden.
    Håkansson, N.
    Karolinska Inst, Inst Environm Med, Unit Nutr Epidemiol, SE-17177 Stockholm, Sweden.
    Bäck, M.
    Karolinska Inst, Ctr Mol Med, Dept Med, Stockholm, Sweden;Karolinska Univ Hosp, Dept Cardiol, Stockholm, Sweden.
    Coffee consumption and risk of aortic valve stenosis: A prospective study2018Inngår i: NMCD. Nutrition Metabolism and Cardiovascular Diseases, ISSN 0939-4753, E-ISSN 1590-3729, Vol. 28, nr 8, s. 803-807Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background and aims: Coffee contains many biologically active compounds with potential adverse or beneficial effects on the cardiovascular system. Whether coffee consumption is associated with the risk of aortic valve stenosis (AVS) is unknown. The purpose of this study was therefore to examine the association between coffee consumption and AVS incidence.

    Methods and results: This prospective study included 71 178 men and women who provided information on their coffee consumption through a questionnaire at baseline. Incident cases of AVS were identified through linkage with the Swedish National Patient and Cause of Death Registers. During a mean follow-up of 15.2 years, 1295 participants (777 men and 518 women) were diagnosed with AVS. Coffee consumption was positively associated with risk of AVS in a dose - response manner after adjustment for age, sex, smoking, and other risk factors (P-trend = 0.005). The multivariable hazard ratios were was 1.11 (95% confidence interval 1.04 - 1.19) per 2 cups/day increase of coffee consumption and 1.65 (95% confidence interval 1.10 - 2.48) when comparing the highest (>= 6 cups/day) with the lowest (<0.5 cup/day) category of coffee consumption. The association was not modified by other risk factors.

    Conclusions: This study provides novel evidence that high coffee consumption is associated with an increased risk of AVS.

  • 9.
    Lind, Lars
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk epidemiologi.
    Strand, Robin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Kullberg, Joel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi. Antaros Med AB, BioVenture Hub, Mölndal, Sweden.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi. Antaros Med AB, BioVenture Hub, Mölndal, Sweden.
    Relationship between endothelium-dependent vasodilation and fat distribution using the new "imiomics" image analysis technique2019Inngår i: NMCD. Nutrition Metabolism and Cardiovascular Diseases, ISSN 0939-4753, E-ISSN 1590-3729, Vol. 29, nr 10, s. 1077-1086Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background and aims: We investigated how vasoreactivity in the brachial artery and the forearm resistance vessels were related to fat distribution and tissue volume, using both traditional imaging analysis and a new technique, called “Imiomics”, whereby vasoreactivity was related to each of the >2M 3D image elements included in the whole-body magnetic resonance imaging (MRI).

    Methods and results: In 326 subjects in the Prospective investigation of Obesity, Energy and Metabolism (POEM) study (all aged 50 years), endothelium-dependent vasodilation was measured by acetylcholine infusion in the brachial artery (EDV) and flow-mediated vasodilation (FMD). Fat distribution was evaluated by dual-energy X-ray absorptiometry (DXA) and magnetic resonance imaging (MRI). EDV, but not FMD, was significantly related to total fat mass, liver fat, subcutaneous (SAT) and visceral (VAT) adipose tissue in a negative fashion in women, but not in men. Using Imiomics, an inverse relationship was seen between EDV and a local tissue volume of SAT in both the upper part of the body, as well as the gluteo-femoral part and the medial parts of the legs in women. Also the size of the liver, heart and VAT was inversely related to EDV. In men, less pronounced relationships were seen. FMD was also significantly related to local tissue volume of upper-body SAT and liver fat in women, but less so in men.

    Conclusion: EDV, and to a lesser degree also FMD, were related to liver fat, SAT and VAT in women, but less so in men. Imiomics both confirmed findings from traditional methods and resulted in new, more detailed results.

  • 10. Lindi, Virpi
    et al.
    Schwab, Ursula
    Louheranta, Anne
    Vessby, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Hermansen, Kjeld
    Tapsell, Linda
    Riccardi, Gabriele
    Rivellese, Angela A
    Laakso, Markku
    Uusitupa, Matti I J
    The G-250A polymorphism in the hepatic lipase gene promoter is associated with changes in hepatic lipase activity and LDL cholesterol: The KANWU Study2008Inngår i: NMCD. Nutrition Metabolism and Cardiovascular Diseases, ISSN 0939-4753, E-ISSN 1590-3729, Vol. 18, nr 2, s. 88-95Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background and aims: Hepatic lipase (HL) catalyzes the hydrolysis of triglycerides and phospholipids from lipoproteins, and promotes the hepatic uptake of tipoproteins. A common G-250A polymorphism in the promoter of the hepatic lipase gene (LIPC) has been described. The aim was to study the effects of the G-250A polymorphism on HL activity, serum lipid profile and insulin sensitivity. Methods and results: Altogether 151 healthy subjects (age 49 +/- 8 years, BMI 26.5 +/- 3.0 kg/m(2)) were randomly assigned for 3 months to an isoenergetic diet containing either a high proportion of saturated fatty acids (SFA diet) or monounsaturated fatty acids (MUFA diet). Within groups there was a second random assignment to supplements with fish oil (3.6 g n-3 FA/day) or placebo. At baseline, the A-250A genotype was associated with high serum LDL cholesterol concentration (P = 0.030 among three genotypes). On the MUFA diet carriers of the A-250A genotype presented a greater decrease in LDL cholesterol concentration than subjects with other genotypes (P = 0.007 among three genotypes). The rare -250A allele was related to Low HL activity (P < 0.001 among three genotypes). The diet did not affect the levels of HL activity among the genotypes. Conclusion: The A-250A genotype of the LIPC gene was associated with high LDL cholesterol concentration, but the MUFA-enriched diet reduced serum LDL cholesterol concentration especially in subjects with the A-250A genotype.

  • 11. Lundman, Pia
    et al.
    Boquist, Susanna
    Samnegård, Ann
    Bennermo, Marie
    Held, Claes
    Department of Cardiology, Karolinska University Hospital, Karolinska Institutet, Stockholm.
    Ericsson, Carl-Göran
    Silveira, Angela
    Hamsten, Anders
    Tornvall, Per
    A high-fat meal is accompanied by increased plasma interleukin-6 concentrations2007Inngår i: NMCD. Nutrition Metabolism and Cardiovascular Diseases, ISSN 0939-4753, E-ISSN 1590-3729, Vol. 17, nr 3, s. 195-202Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND AND AIM: Enhanced and prolonged postprandial lipaemia is associated with coronary heart disease (CHD). However, the mechanisms linking postprandial lipaemia to the increased risk of atherosclerosis and CHD remain to be determined. The aim of the present study was to examine the effects of a high-fat meal on plasma levels of the pro-inflammatory cytokine interleukin-6 (IL-6) and cellular adhesion molecules in CHD patients and control subjects. METHODS AND RESULTS: Forty-one middle-aged men with premature CHD and 26 healthy male controls were investigated. The plasma triglyceride response to the high-fat meal was significantly greater among cases than controls. The oral fat load induced a twofold increase in plasma concentrations of IL-6, an increase that was similar in CHD patients and control subjects. No changes could be detected in plasma concentrations of cellular adhesion molecules in response to postprandial lipaemia in either CHD patients or control subjects. CONCLUSION: The results of the present study suggest that a high-fat meal affects mechanisms that induce increased inflammatory activity, which is recognised as a key modulator in the development of atherosclerosis and CHD. However, the increased levels of plasma IL-6 appear not to be determined by the magnitude of the postprandial triglyceridaemia.

  • 12.
    Malmström, H.
    et al.
    Karolinska Inst, Inst Environm Med, Epidemiol Unit, Stockholm, Sweden..
    Wandell, P. E.
    Karolinska Inst, Div Family Med, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden..
    Holzmann, M. J.
    Karolinska Univ Hosp, Dept Emergency Med, Huddinge, Sweden.;Karolinska Inst, Dept Internal Med, Solna, Sweden..
    Ärnlöv, Johan
    Univ Uppsala Hosp, Dept Med Sci, Uppsala, Sweden.;Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden..
    Jungner, I.
    Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden.;CALAB Res, Stockholm, Sweden..
    Hammar, N.
    Karolinska Inst, Inst Environm Med, Epidemiol Unit, Stockholm, Sweden.;AstraZeneca R&D, Med Evidence & Observat Res, Molndal, Sweden..
    Walldius, G.
    Karolinska Inst, Inst Environm Med, Unit Cardiovasc Epidemiol, Stockholm, Sweden..
    Carlsson, A. C.
    Karolinska Inst, Inst Environm Med, Epidemiol Unit, Stockholm, Sweden.;Univ Uppsala Hosp, Dept Med Sci, Uppsala, Sweden..
    Low fructosamine and mortality - A long term follow-up of 215,011 non-diabetic subjects in the Swedish AMORIS study2016Inngår i: NMCD. Nutrition Metabolism and Cardiovascular Diseases, ISSN 0939-4753, E-ISSN 1590-3729, Vol. 26, nr 12, s. 1120-1128Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background and aims: Both high and low fasting glucose has been associated with an increased mortality among individuals without diabetes. This J-shaped association has also been shown for HbA1c in relation to all-cause mortality. High fructosamine is associated with increased mortality. In this study we aim to evaluate if low fructosamine is also associated with increased mortality in non-diabetic subjects. Methods and results: We included 215,011 subjects from the AMORIS cohort undergoing occupational health screening or primary care in Stockholm, Sweden. Cause specific mortality was obtained from the Swedish Cause-of-Death Register by record linkage. Hazard ratios for the lowest decile of fructosamine were estimated by Cox regression for all-cause (n = 41,388 deaths) and cause-specific mortality during 25 years of follow-up. We observed gradually increased mortality with lower fructosamine in a large segment of the population. In the lowest decile of fructosamine the sex, age, social class and calendar adjusted hazard ratio was 1.20 (95% CI; 1.18-1.27) compared to deciles 2-9. This increased mortality was attenuated after adjustment for six other biomarkers (HR = 1.11 (95% CI; 1.07-1.15)). Haptoglobin, an indicator of chronic inflammation, made the greatest difference in the point estimate. In sensitivity analyses we found an association between low fructosamine and smoking and adjustment for smoking further attenuated the association between low fructosamine and mortality. Conclusion: Low levels of fructosamine in individuals without diabetes were found to be associated with increased mortality. Smoking and chronic inflammation seem to at least partially explain this association but an independent contribution by low fructosamine cannot be excluded.

  • 13.
    Vessby, Bengt
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Ahrén, B
    Warensjö, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Lindgärde, Folke
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Plasma lipid fatty acid composition, desaturase activities and insulin sensitivity in Amerindian women2012Inngår i: NMCD. Nutrition Metabolism and Cardiovascular Diseases, ISSN 0939-4753, E-ISSN 1590-3729, Vol. 22, nr 3, s. 176-181Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND AND AIMS: Two Amerindian populations - Shuar women living in the Amazonian rain forest under traditional conditions and urbanized women in a suburb of Lima were studied. The fatty acid composition in plasma lipids and the relationships between fatty acid composition and metabolic variables were studied, as well as in a reference group of Swedish women.

    METHODS AND RESULTS: Fasting plasma was used for analyses of glucose, insulin, leptin and fatty acid composition. Women in Lima had more body fat, higher fasting insulin and leptin and lower insulin sensitivity than the Shuar women, who had insulin sensitivity similar to Swedish women. Shuar women had very high proportions (mean; SD) of palmitoleic (13.2; 3.9%) and oleic (33.9; 3.7%) acids in the plasma cholesteryl esters with very low levels of linoleic acid (29.1; 6.1 3%), as expected on a low fat, high carbohydrate diet. The estimated activity of delta 9 (SCD-1) desaturase was about twice as high in the Shuar compared with Lima women, suggesting neo lipogenesis, while the delta 5 desaturase activity did not differ. The Lima women, as well as the Swedish, showed strong positive correlations between SCD-1 activity on the one hand and fasting insulin and HOMA index on the other. These associations were absent in the Shuar women.

    CONCLUSIONS: The high SCD-1 activity in the Shuar women may reflect increased lipogenesis in adipose tissue. It also illustrates how a low fat diet rich in non-refined carbohydrates can be linked to a good metabolic situation.

  • 14.
    Warensjö, Eva
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Gustafsson, Inga-Britt
    Mohsen, Rawya
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Cederholm, Tommy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Vessby, Bengt
    Effects of saturated and unsaturated fatty acids on estimated desaturase activities during a controlled dietary intervention2008Inngår i: NMCD. Nutrition Metabolism and Cardiovascular Diseases, ISSN 0939-4753, E-ISSN 1590-3729, Vol. 18, nr 10, s. 683-690Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background and aims

    Direct measurement of desaturase activities are difficult to obtain in humans. Consequently, surrogate measures of desaturase activity (estimated desaturase activities) have been frequently used in observational studies, and estimated Δ9- (or stearoyl-CoA-desaturase (SCD)), Δ6- and Δ5-desaturase activities have been associated with cardiometabolic disease. Data on how the markers of desaturase activities are modified by changes in dietary fat quality are lacking and therefore warrant examination.

    Methods and results

    In a two-period (three weeks) strictly controlled cross-over study, 20 subjects (six women and 14 men) consumed a diet high in saturated fat (SAT-diet) and a rapeseed oil diet (RO-diet), rich in oleic acid (OA), linoleic acid (LA) and α-linolenic acid (ALA). Estimated desaturase activities were calculated as precursor to product FA ratios in serum cholesteryl esters and phospholipids. The estimated SCD [16:1 n-7/16:0] and Δ6-desaturase [20:3 n-6/18:2 n-6] was significantly higher while Δ5-desaturase [20:4 n-6/20:3 n-6] was significantly lower in the SAT-diet (P<0.001 for all), compared to the RO-diet. The serum proportions of palmitic, stearic, palmitoleic and dihomo-γ-linolenic acids were significantly higher in the SAT-diet while the proportions of LA and ALA were significantly higher in the RO-diet.

    Conclusion

    This is the first study to demonstrate that surrogate measures of desaturase activities change as a consequence of an alteration in dietary fat quality. Both the [16:1/16:0]-ratio and 16:1 seem to reflect changes in saturated fat intake and may be useful markers of saturated fat intake in Western countries.

  • 15.
    Warensjö, Eva
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Öhrvall, Margareta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Vessby, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Fatty acid composition and estimated desaturase activities are associated with obesity and lifestyle variables in men and women2006Inngår i: NMCD. Nutrition Metabolism and Cardiovascular Diseases, ISSN 0939-4753, E-ISSN 1590-3729, Vol. 16, nr 2, s. 128-136Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    It is known that the fatty acid (FA) composition in serum cholesteryl esters to a certain extent mirrors not only the FA composition of dietary fat, but also the endogenous FA synthesis, where desaturases play an important part. A surrogate measure of Δ9-, Δ6- and Δ5-desaturase activity can be calculated as a [product:precursor] fatty acid ratio. Δ9-Desaturase activity is known to be high in conditions like diabetes, atherosclerosis and obesity. The aim of the present study was to relate the proportions of individual fatty acids in serum cholesteryl esters, as well as estimated desaturase ratios to markers of obesity and lifestyle variables (smoking, physical activity and dietary fat). We also studied gender differences. These relationships were studied in a reference population consisting of men (n=554) and women (n=295) who took part in a health survey concerning coronary heart disease in Sweden. We found positive and significant correlations between markers of obesity and the proportions of 16:0, 16:1 (n-7), 18:0, 18:3 (n-6), 20:3 (n-6), 20:4 (n-6), 20:5 (n-3), Δ9 and Δ6 activities, and an inverse correlation to Δ5 activity and 18:2 (n-6). These relationships were independent of age and physical activity and in some cases of body mass index (BMI). For each standard deviation (SD) increase of Δ9 and Δ6 activities, the risk of being overweight was increased by about 60%, whereas the risk was reduced to about 30% for every SD increase of Δ5 activity. Women were found to have significantly higher levels of Δ9 and lower levels of Δ6 desaturase activities than men. In conclusion, this study shows that a changed FA profile in serum cholesteryl esters and estimated desaturase activities are associated with obesity and lifestyle factors in men and women.

  • 16.
    Xu, H.
    et al.
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Div Renal Med, SE-14186 Stockholm, Sweden.;Karolinska Inst, Dept Clin Sci Intervent & Technol, Div Baxter Novum, SE-14186 Stockholm, Sweden..
    Rossi, M.
    Princess Alexandra Hosp, Ctr Kidney Dis Res, Brisbane, Qld 4102, Australia.;Kings Coll London, Div Diabet & Nutr Sci, London WC2R 2LS, England..
    Campbell, K. L.
    Princess Alexandra Hosp, Ctr Kidney Dis Res, Brisbane, Qld 4102, Australia.;Bond Univ, Fac Hlth Sci & Med, Robina, Australia..
    Sencion, G. L.
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Div Renal Med, SE-14186 Stockholm, Sweden.;Karolinska Inst, Dept Clin Sci Intervent & Technol, Div Baxter Novum, SE-14186 Stockholm, Sweden..
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi. Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden..
    Cederholm, Tommy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Sjögren, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Riserus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Lindholm, B.
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Div Renal Med, SE-14186 Stockholm, Sweden.;Karolinska Inst, Dept Clin Sci Intervent & Technol, Div Baxter Novum, SE-14186 Stockholm, Sweden..
    Carrero, J. J.
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Div Renal Med, SE-14186 Stockholm, Sweden.;Karolinska Inst, Dept Clin Sci Intervent & Technol, Div Baxter Novum, SE-14186 Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, SE-14186 Stockholm, Sweden..
    Excess protein intake relative to fiber and cardiovascular events in elderly men with chronic kidney disease2016Inngår i: NMCD. Nutrition Metabolism and Cardiovascular Diseases, ISSN 0939-4753, E-ISSN 1590-3729, Vol. 26, nr 7, s. 597-602Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background and aims: The elevated cardiovascular (CVD) risk observed in chronic kidney disease (CKD) may be partially alleviated through diet. While protein intake may link to CVD events in this patient population, dietary fiber has shown cardioprotective associations. Nutrients are not consumed in isolation; we hypothesize that CVD events in CKD may be associated with dietary patterns aligned with an excess of dietary protein relative to fiber. Methods and Results: Prospective cohort study from the Uppsala Longitudinal Study of Adult Men. Included were 390 elderly men aged 70-71 years with CKD and without clinical history of CVD. Protein and fiber intake, as well as its ratio, were calculated from 7-day dietary records. Cardiovascular events were registered prospectively during a median follow-up of 9.1 (inter-quartile range, 4.5-10.7) years. The median dietary intake of protein and fiber was 66.7 (60.7-71.1) and 16.6 (14.5-19.1) g/day respectively and the protein-to-fiber intake ratio was 4.0 (3.5-4.7). Protein-to-fiber intake ratio was directly associated with serum C-reactive protein levels. During follow-up, 164 first-time CVD events occurred (incidence rate 54.5/1000 per year). Protein-fiber intake ratio was an independent risk factor for CVD events [adjusted hazard ratio, HR per standard deviation increase (95% confidence interval, CI) 1.33 (1.08, 1.64)]. Although in opposing directions, dietary protein [1.18 (0.97, 1.44)], dietary fiber alone [0.81 (0.64, 1.02)], were not significantly associated with CVD events. Conclusions: An excess of dietary protein relative to fiber intake was associated with the incidence of cardiovascular events in a homogeneous population of older men with CKD.

  • 17.
    Xu, H.
    et al.
    Karolinska Inst, Div Renal Med, Stockholm, Sweden.;Karolinska Inst, Div Baxter Novum, Stockholm, Sweden..
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi. Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden..
    Sandhagen, Bo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Lindholm, B.
    Karolinska Inst, Div Renal Med, Stockholm, Sweden.;Karolinska Inst, Div Baxter Novum, Stockholm, Sweden..
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Carrero, J. J.
    Karolinska Inst, Div Renal Med, Stockholm, Sweden.;Karolinska Inst, Div Baxter Novum, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden..
    Lipophilic index, kidney function, and kidney function decline2016Inngår i: NMCD. Nutrition Metabolism and Cardiovascular Diseases, ISSN 0939-4753, E-ISSN 1590-3729, Vol. 26, nr 12, s. 1096-1103Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background and aims: Unhealthy dietary fats are associated with faster kidney function decline. The cell membrane composition of phospholipid fatty acids (FAs) is a determinant of membrane fluidity and rheological properties. These properties, which have been linked to kidney damage, are thought to be reflected by the lipophilic index (LI). We prospectively investigated the associations of LI with kidney function and its decline. Methods and results: Observational study from the Prospective Investigation of Vasculature in Uppsala Seniors including 975 men and women with plasma phospholipid FAs composition and cystatin-C estimate glomerular filtration rate (eGFR). Of these, 780 attended reexamination after 5 years, and eGFR changes were assessed. Participants with a 5-year eGFR reduction >= 30% were considered chronic kidney disease (CKD) progressors (n = 198). LI was calculated as the sum of the products of the FA proportions with the respective FAs melting points. Blood rheology/viscosity measurements were performed in a random subsample of 559 subjects at baseline. Increased LI showed a statistically significant but overall weak association with blood, plasma viscosity (both Spearman rho = 0.16, p < 0.01), and erythrocyte deformability (rho = -0.09, p < 0.05). In cross-sectional analyses, LI associated with lower eGFR (regression coefficient 3.00 ml/min/1.73 m(2) 1-standard deviation (SD) increment in LI, 95% CI: -4.31, -1.69, p < 0.001). In longitudinal analyses, LI associated with a faster eGFR decline (-2.13 [95% CI -3.58, -0.69] ml/min/1.73 m(2), p < 0.01) and with 32% increased odds of CKD progression (adjusted OR 1.32 [95%, CI 1.05-1.65]). Conclusions: A high LI was associated with lower kidney function, kidney function decline, and CKD progression.

  • 18.
    Yuan, Shuai
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper. Karolinska Inst, Inst Environm Med, Unit Cardiovasc & Nutr Epidemiol, Nobelsvag 13, S-17177 Stockholm, Sweden.
    Larsson, Susanna C.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi. Karolinska Inst, Inst Environm Med, Unit Cardiovasc & Nutr Epidemiol, Nobelsvag 13, S-17177 Stockholm, Sweden.
    No association between coffee consumption and risk of atrial fibrillation: A Mendelian randomization study2019Inngår i: NMCD. Nutrition Metabolism and Cardiovascular Diseases, ISSN 0939-4753, E-ISSN 1590-3729, Vol. 29, nr 11, s. 1185-1188Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background and aims: Some observational studies have found that habitual coffee and caffeine consumption might reduce the risk of atrial fibrillation (AF). We conducted a two-sample Mendelian randomization study to explore the potential association between coffee consumption and AF.

    Methods and results: This study was based on summary-level data from the Atrial Fibrillation Consortium, including 588 190 individuals (65 446 cases and 522 744 non-cases). Nine single-nucleotide polymorphisms associated with coffee consumption at significance level of P < 5 x 10(-8) were used as instrumental variables and were obtained from a genome-wide association study that included up to 375 833 individuals. The odds ratio of AF per genetically-predicted 50% increase of coffee consumption was 0.98 (95% confidence interval, 0.88, 1.10; P = 0.80) in the standard inverse-variance weighted analysis. Results were consistent in sensitivity analyses using the weighted median and MR-Egger methods, and no directional pleiotropy (P = 0.37) was observed. Moreover, complementary analyses that separated the coffee-related single-nucleotide polymorphisms based on their association with blood levels of caffeine metabolites (lower, higher, unrelated or unknown association) revealed no association with AF.

    Conclusions: This study does not support a causal association between habitual coffee consumption and risk of AF. 

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