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Biomedical subjects

Ulf Risérus

Publications and source records attributed to Ulf Risérus.

15 recordsLinked to original sources
PubMed2006

Antioxidant intake, oxidative stress and inflammation among immigrant women from the Middle East living in Sweden: associations with cardiovascular risk factors.

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 F(2)-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 alpha-tocopherol, but not gamma-tocopherol levels, was lower 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 role 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.

Adult↗
PubMed2006

Trans fatty acids and insulin resistance.

Since trans fatty acids (TFA) might interfere with cell membrane functions, there are reasons to believe that high TFA intakes could affect insulin sensitivity and consequently diabetes risk. It is possible that low amounts of TFA consumed during long time-periods might be clinically relevant. Data from controlled intervention studies investigating the effects of TFA on insulin sensitivity are reviewed. The results show no significant effect of TFA on insulin sensitivity in lean healthy subjects. However, there is some evidence that TFA could impair insulin sensitivity compared to unsaturated fat in insulin resistant or diabetic individuals. This is especially true for conjugated TFA, i.e. conjugated linoleic acid (CLA), which clearly impairs insulin sensitivity. In fact, the effect of CLA on insulin action is the most dramatic adverse effect described for a dietary fatty acid. The inconsistent effect of TFA as a group might partly be due to methodological limitations (e.g. few studies, short duration or small sample size) and differences between studies in design, type and amount of TFA used. Large controlled trials have been required to demonstrate adverse effects of saturated fat on insulin sensitivity, and similar efforts will probably be needed to clarify the effect of TFA on insulin sensitivity.

Clinical Trials as Topic↗
PubMed2006

Clinical value of the metabolic syndrome for long term prediction of total and cardiovascular mortality: prospective, population based cohort study.

OBJECTIVES: To find out if the presence of the metabolic syndrome increases the risk of subsequent total and cardiovascular mortality, taking into account established risk factors for cardiovascular disease. DESIGN: Prospective cohort study. SETTING: General population. PARTICIPANTS: A community based sample of 2322 men followed since 1970 for a maximum of 32.7 years, investigated at ages 50 and 70. MAIN OUTCOME MEASURES: The relations of the metabolic syndrome defined by the national cholesterol education programme (NCEP) of the US National Heart, Lung, and Blood Institute or criteria of the World Health Organization (WHO) to subsequent total and cardiovascular mortality. RESULTS: When adding the metabolic syndrome to models with established risk factors for cardiovascular disease (smoking, diabetes, hypertension, and serum cholesterol) at age 50, presence of the metabolic syndrome as defined in the NCEP significantly predicted total and cardiovascular mortality (Cox proportional hazard ratios 1.36, 95% confidence interval 1.17 to 1.58; and 1.59, 1.29 to 1.95, respectively). The metabolic syndrome added prognostic information to that of the established risk factors for cardiovascular disease (likelihood ratio tests, P < 0.0001 for both outcomes). Similar results were obtained in a subsample without diabetes or manifest cardiovascular disease. CONCLUSIONS: In a large, community based sample of middle aged men, the presence of the metabolic syndrome according to the definition of the NCEP gave long term prognostic information regarding total and cardiovascular mortality if the status of established risk factors for cardiovascular disease was known. If confirmed this may indicate clinical value in diagnosing the metabolic syndrome.

Aged↗
PubMed2005

A Doppler-derived index of combined left ventricular systolic and diastolic function is an independent predictor of cardiovascular mortality in elderly men.

BACKGROUND: Few studies on echocardiographic and Doppler indices of cardiac function as predictors for cardiovascular mortality have been performed in the general population. The novel myocardial performance index (MPI, also denoted as Tei-Doppler index) has been suggested to reflect both left ventricular (LV) systolic and diastolic function. METHODS: We investigated whether 10 different echocardiographic and Doppler indices of cardiac function predicted cardiovascular mortality by using a population-based cohort of 583 seventy-year-old men with a mean follow-up time of 6.8 years. RESULTS: In a multivariate Cox proportional hazard analysis for a 1-SD increase including LV ejection fraction, E/A ratio, MPI, and traditional cardiovascular risk factors (previous myocardial infarction, hyperlipidemia, hypertension, diabetes, smoking status, and LV hypertrophy), both ejection fraction (hazard ratio [HR] = 0.59, 95% CI 0.38-0.90, P < .05) and MPI (HR = 2.92, 95% CI 1.71-4.97, P < .0001) were found to be independent predictors for cardiovascular mortality. After excluding subjects with coronary heart disease, only MPI remained a significant predictor (HR = 2.18, 95% CI 1.11-4.27, P < .03, for 1-SD increase), and neither ejection fraction, E/A ratio, nor any of the cardiovascular risk factors remained significant predictors. CONCLUSION: Myocardial performance index is a predictor for cardiovascular mortality, independent of other measurements of cardiac function and of traditional cardiovascular risk factors in elderly men free from coronary heart disease.

Aged↗
PubMed2005

Rosiglitazone increases indexes of stearoyl-CoA desaturase activity in humans: link to insulin sensitization and the role of dominant-negative mutation in peroxisome proliferator-activated receptor-gamma.

Fatty acid desaturases such as steaoryl-CoA desaturase (SCD) convert saturated to unsaturated fatty acids and are involved in lipogenesis. Observational and animal data suggest that SCD-1 activity is related to insulin sensitivity. However, the effects of insulin-sensitizing drugs on SCD gene expression and desaturase activities are unknown in humans. In a randomized, placebo-controlled, double-blind, crossover study, 24 subjects with type 2 diabetes and one subject with partial lipodystrophy and diabetes due to dominant-negative mutation in the peroxisome proliferator-activated receptor-gamma (PPARgamma) gene (P467L) received placebo and rosiglitazone for 3 months. SCD gene expression in adipose tissue was determined in 23 subjects, and in a representative subgroup (n = 10) we assessed fatty acid composition in fasting plasma triglycerides to estimate SCD and delta6- and delta5-desaturase activity, using product-to-precursor indexes. SCD mRNA expression increased by 48% after rosiglitazone (P < 0.01). SCD and delta5-desaturase but not delta6-desaturase activity indexes were increased after rosiglitazone versus placebo (P < 0.01 and P < 0.05, respectively). The change in activity index but not the expression of SCD was associated with improved insulin sensitivity (r = 0.73, P < 0.05). In the P467L PPARgamma carrier, SCD and delta5-desaturase activity indexes were exceptionally low but were restored (52- and 15-fold increases, respectively) after rosiglitazone treatment. This study shows for the first time that rosiglitazone increases SCD activity indexes and gene expression in humans. An increased SCD activity index may reflect increased lipogenesis and might contribute to insulin sensitization by rosiglitazone. The restored SCD activity index after rosiglitazone in PPARgamma mutation supports a pivotal role of PPARgamma function in SCD regulation.

Diabetes Mellitus, Type 2↗
PubMed2004

Myocardial performance index, a Doppler-derived index of global left ventricular function, predicts congestive heart failure in elderly men.

AIMS: There is limited data on echocardiographic and Doppler indices of cardiac function as predictors for congestive heart failure (CHF) in the general population. Myocardial performance index (MPI, also denoted TEI-Doppler index) reflects both left ventricular (LV) systolic and diastolic function. METHODS AND RESULTS: We compared eight different echocardiographic and Doppler indices of cardiac function as predictors of CHF using a population-based cohort of 552 seventy-year-old men without CHF and significant valve disease at baseline (median follow-up time 8.2 years). In a stepwise multivariable Cox proportional-hazard analysis including the different indices of cardiac function, high MPI (above the 90th percentile of MPI [> or =0.91]), abnormal LV wall motion score index and a pseudo-normalized/restrictive E/A-ratio pattern independently predicted future CHF morbidity. After adding traditional CHF risk factors (age, previous myocardial infarction, hypertension, diabetes mellitus, hyperlipidaemia, smoking, LV hypertrophy and body mass index) to the above model, only a high MPI remained a significant predictor (hazard ratio 4.72, 95% CI 1.75-12.76, p=0.002). CONCLUSION: MPI provides important prognostic information for the risk of future CHF, beyond other measurements of cardiac function and traditional heart failure risk factors in elderly men. MPI seems to be a clinically relevant indicator of cardiac function and may prove to be a valuable tool in assessing the risk of future CHF.

Aged↗
PubMed2004

Effects of cis-9,trans-11 conjugated linoleic acid supplementation on insulin sensitivity, lipid peroxidation, and proinflammatory markers in obese men.

BACKGROUND: We recently showed that trans-10,cis-12 (t10,c12) conjugated linoleic acid (CLA) causes insulin resistance in obese men. However, metabolic effects of the c9,t11 CLA isomer are still unknown in obese men. Because c9,t11 CLA is the predominant CLA isomer in foods and is included in dietary weight-loss products, it is important to conduct randomized controlled studies that use c9,t11 CLA preparations. OBJECTIVE: We investigated the effects of c9,t11 CLA supplementation on insulin sensitivity, body composition, and lipid peroxidation in a group at high risk for cardiovascular disease. DESIGN: In a randomized, double-blind, placebo-controlled study, 25 abdominally obese men received 3 g c9,t11 CLA/d or placebo (olive oil). Before and after 3 mo of supplementation, we assessed insulin sensitivity (hyperinsulinemic euglycemic clamp), lipid metabolism, body composition, and urinary 8-iso-prostaglandin F(2alpha) (a major F(2)-isoprostane) and 15-keto-dihydro-prostaglandin F(2alpha), markers of in vivo oxidative stress and inflammation, respectively. RESULTS: All subjects completed the study. Compared with placebo, c9,t11 CLA decreased insulin sensitivity by 15% (P < 0.05) and increased 8-iso-prostaglandin F(2alpha) and 15-keto-dihydro-prostaglandin F(2alpha) excretion by 50% (P < 0.01) and 15% (P < 0.05), respectively. The decreased insulin sensitivity was independent of changes in serum lipids, glycemia, body mass index, and body fat but was abolished after adjustment for changes in 8-iso-prostaglandin F(2alpha) concentrations. There were no differences between groups in body composition. CONCLUSIONS: A CLA preparation containing the purified c9,t11 CLA isomer increased insulin resistance and lipid peroxidation compared with placebo in obese men. Because c9,t11 CLA occurs in commercial supplements as well as in the diet, the present results should be confirmed in larger studies that also include women.

Administration, Oral↗
PubMed2004

Sagittal abdominal diameter is a strong anthropometric marker of insulin resistance and hyperproinsulinemia in obese men.

OBJECTIVE: It is clinically important to find noninvasive markers of insulin resistance and hyperproinsulinemia because they both predict cardiovascular and diabetes risk. Sagittal abdominal diameter (SAD) or "supine abdominal height" is a simple anthropometric measure previously shown to predict mortality in men, but its association with insulin resistance and hyperproinsulinemia is unknown. RESEARCH DESIGN AND METHODS: In a common high-risk group of 59 moderately obese men (aged 35-65 years, BMI 32.6 +/- 2.3 kg/m(2)), we determined anthropometry (SAD, BMI, waist girth, and waist-to-hip ratio [WHR]); insulin sensitivity (euglycemic-hyperinsulinemic clamp); and plasma concentrations of intact proinsulin, specific insulin, C-peptide, glucose, and serum IGF binding protein-1 (IGFBP-1). To compare SAD with other anthropometric measures, univariate and multiple regression analyses were used to determine correlations between anthropometric and metabolic variables. RESULTS: SAD showed stronger correlations to all measured metabolic variables, including insulin sensitivity, than BMI, waist girth, and WHR. SAD explained the largest degree of variation in insulin sensitivity (R(2) = 0.38, P < 0.0001) compared with other anthropometric measures. In multiple regression analyses, including all anthropometric measures, SAD was the only independent anthropometric predictor of insulin resistance (P < 0.001) and hyperproinsulinemia (P < 0.001). CONCLUSIONS: In obese men, SAD seems to be a better correlate of insulin resistance and hyperproinsulinemia (i.e., cardiovascular risk) than other anthropometric measures. In overweight and obese individuals, SAD could represent a simple, cheap, and noninvasive tool that could identify the most insulin resistant in both the clinic and clinical trials evaluating insulin sensitizers. These results need confirmation in larger studies that also include women and lean subjects.

Abdomen↗
PubMed2004

Metabolic effects of conjugated linoleic acid in humans: the Swedish experience.

Conjugated linoleic acid (CLA) comprises a group of unsaturated fatty acid isomers with a variety of biological effects. CLA reduces body fat accumulation in animal models and has been ascribed significant effects on lipid and glucose metabolism. It has been suggested that the trans-10,cis-12 isomer is the active isomer with regard to antiobesity and insulin-sensitizing properties. The metabolic effects in humans are not well characterized. We have investigated and published the effects of CLA (given as the commercially available mixture and as the purified trans-10,cis-12 isomer) on anthropometry, lipid and glucose metabolism, and markers of lipid peroxidation. The results from those studies indicate that CLA might slightly decrease body fat in humans, particularly abdominal fat, but there is no effect on body weight or body mass index. There is no simultaneous improvement in lipid or glucose metabolism. Rather, the trans-10,cis-12 CLA isomer unexpectedly caused significant impairment of the peripheral insulin sensitivity as well as of blood glucose and serum lipid concentrations. In addition, CLA markedly elevated lipid peroxidation. Thus, the metabolic effects of CLA in humans seem complex, and further studies, especially of specific isomers and of longer duration, are needed.

Adipose Tissue↗
PubMed2003

CLA and body weight regulation in humans.

CLA comprises a group of unsaturated FA isomers with a variety of biological effects in experimental animals. CLA reduces body fat accumulation in animal models and has been suggested to have significant effects on lipid and glucose metabolism, e.g., antidiabetic effects in obese Zucker rats. It has been proposed that the trans10-cis12 isomer is the active isomer associated with the antiobesity and insulin-sensitizing properties of CLA. The metabolic effects in humans in general, and isomer-specific effects specifically, are not well characterized. In a series of controlled studies in humans, we investigated the effects of CLA (given as the commercially available mixture of isomers and as the purified trans10-cis12 CLA isomer) on anthropometry, lipid and glucose metabolism, and markers of lipid peroxidation. Preliminary results indicate that CLA may slightly decrease body fat in humans also, particularly abdominal fat, but there is no effect on body weight or body mass index. There is no simultaneous improvement in lipid or glucose metabolism. Rather, the trans10-cis12 CLA isomer unexpectedly caused significant impairment of the peripheral insulin sensitivity as well as of blood glucose and serum lipid levels. In addition, CLA markedly elevated lipid peroxidation. Thus, the metabolic effects of CLA in humans seem complex; further studies, especially of isomer-specific effects and for longer time periods, are warranted.

Body Weight↗
PubMed2002

Supplementation with conjugated linoleic acid causes isomer-dependent oxidative stress and elevated C-reactive protein: a potential link to fatty acid-induced insulin resistance.

BACKGROUND: Conjugated linoleic acids (CLAs), a group of fatty acids shown to have beneficial effects in animals, are also used as weight loss supplements. Recently, we reported that the t10c12 CLA-isomer caused insulin resistance in abdominally obese men via unknown mechanisms. The aim of the present study was to examine whether CLA has isomer-specific effects on oxidative stress or inflammatory biomarkers and to investigate the relationship between these factors and induced insulin resistance. METHODS AND RESULTS: In a double-blind placebo-controlled trial, 60 men with metabolic syndrome were randomized to one of 3 groups receiving t10c12 CLA, a CLA mixture, or placebo for 12 weeks. Insulin sensitivity (euglycemic clamp), serum lipids, in vivo lipid peroxidation (determined as urinary 8-iso-PGF(2alpha) [F2-isoprostanes]), 15-ketodihydro PGF(2alpha), plasma vitamin E, plasma C-reactive protein, tumor necrosis factor-alpha, and interleukin-6 were assessed before and after treatment. Supplementation with t10c12 CLA markedly increased 8-iso-PGF(2alpha) (578%) and C-reactive protein (110%) compared with placebo (P<0.0001 and P<0.01, respectively) and independent of changes in hyperglycemia or dyslipidemia. The increases in 8-iso-PGF(2alpha), but not in C-reactive protein, were significantly and independently related to aggravated insulin resistance. Oxidative stress was related to increased vitamin E levels, suggesting a compensatory mechanism. CONCLUSIONS: t10c12 CLA supplementation increases oxidative stress and inflammatory biomarkers in obese men. The oxidative stress seems closely related to induced insulin resistance, suggesting a link between the fatty acid-induced lipid peroxidation seen in the present study and insulin resistance. These unfavorable effects of t10c12 CLA might be of clinical importance with regard to cardiovascular disease, in consideration of the widespread use of dietary supplements containing this fatty acid.

Adult↗
PubMed2002

Treatment with dietary trans10cis12 conjugated linoleic acid causes isomer-specific insulin resistance in obese men with the metabolic syndrome.

OBJECTIVE: Conjugated linoleic acid (CLA) is a group of dietary fatty acids with antiobesity and antidiabetic effects in some animals. The trans10cis12 (t10c12) CLA isomer seems to cause these effects, including improved insulin sensitivity. Whether such isomer-specific effects occur in humans is unknown. The aim of this study was to investigate whether t10c12 CLA or a commercial CLA mixture could improve insulin sensitivity, lipid metabolism, or body composition in obese men with signs of the metabolic syndrome. RESEARCH DESIGN AND METHODS: In a randomized, double-blind controlled trial, abdominally obese men (n = 60) were treated with 3.4 g/day CLA (isomer mixture), purified t10c12 CLA, or placebo. Euglycemic-hyperinsulinemic clamp, serum hormones, lipids, and anthropometry were assessed before and after 12 weeks of treatment. RESULTS: Baseline metabolic status was similar between groups. Unexpectedly, t10c12 CLA increased insulin resistance (19%; P < 0.01) and glycemia (4%; P < 0.001) and reduced HDL cholesterol (-4%; P < 0.01) compared with placebo, whereas body fat, sagittal abdominal diameter, and weight decreased versus baseline, but the difference was not significantly different from placebo. The CLA mixture did not change glucose metabolism, body composition, or weight compared with placebo but lowered HDL cholesterol (-2%; P < 0.05). CONCLUSIONS: These results reveal important isomer-specific metabolic actions of CLA in abdominally obese humans. A CLA-induced insulin resistance has previously been described only in lipodystrophic mice. Considering the use of CLA-supplements among obese individuals, it is important to clarify the clinical consequences of these results, but they also provide physiological insights into the role of specific dietary fatty acids as modulators of insulin resistance in humans.

Adult↗