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91.
  • Ruge, T., et al. (författare)
  • Acute hyperinsulinemia raises plasma interleukin-6 in both nondiabetic and type 2 diabetes mellitus subjects, and this effect is inversely associated with body mass index
  • 2009
  • Ingår i: Metabolism. - 1532-8600 .- 1532-8600. ; 58:6, s. 860-6
  • Tidskriftsartikel (refereegranskat)abstract
    • Hyperinsulinemia is a characteristic of type 2 diabetes mellitus (T2DM) and is believed to play a role in the low-grade inflammation seen in T2DM. The main aim was to study the effect of hyperinsulinemia on adipokines in individuals with different levels of insulin resistance, glycemia, and obesity. Three groups of sex-matched subjects were studied: young healthy subjects (YS; n = 10; mean age, 26 years; body mass index [BMI], 22 kg/m(2)), patients with T2DM (DS; n = 10; 61 years; BMI, 27 kg/m(2)), and age- and BMI-matched controls to DS (CS; n = 10; 60 years; BMI, 27 kg/m(2)). Plasma concentrations of adipokines were measured during a hyperinsulinemic euglycemic clamp lasting 4 hours. Moreover, insulin-stimulated glucose uptake in isolated adipocytes was analyzed to address adipose tissue insulin sensitivity. Plasma interleukin (IL)-6 increased significantly (P < or = .01) in all 3 groups during hyperinsulinemia. However, the increase was smaller in both DS (P = .06) and CS (P < .05) compared with YS (approximately 2.5-fold vs approximately 4-fold). A significant increase of plasma tumor necrosis factor (TNF) alpha was observed only in YS. There were only minor or inconsistent effects on adiponectin, leptin, and high-sensitivity C-reactive protein levels during hyperinsulinemia. Insulin-induced rise in IL-6 correlated negatively to BMI (P = .001), waist to hip ratio (P = .05), and baseline (fasting) insulin (P = .03) and IL-6 (P = .02) levels and positively to insulin-stimulated glucose uptake in isolated adipocytes (P = .07). There was no association with age or insulin sensitivity. In a multivariate analysis, also including T2DM/no T2DM, an independent correlation (inverse) was found only between BMI and fold change of IL-6 (r(2) = 0.41 for model, P < .005). Hyperinsulinemia per se can produce an increase in plasma IL-6 and TNFalpha, and this can potentially contribute to the low-grade inflammation seen in obesity and T2DM. However, obesity seems to attenuate the ability of an acute increase in insulin to further raise circulating levels of IL-6 and possibly TNFalpha.
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92.
  • Ruge, Toralph, et al. (författare)
  • Acute hyperinsulinemia raises plasma interleukin-6 in both nondiabetic and type 2 diabetes mellitus subjects, and this effect is inversely associated with body mass index
  • 2009
  • Ingår i: Metabolism. - : Elsevier BV. - 0026-0495 .- 1532-8600. ; 58:6, s. 860-866
  • Tidskriftsartikel (refereegranskat)abstract
    • Hyperinsulinemia is a characteristic of type 2 diabetes mellitus (T2DM) and is believed to play a role in the low-grade inflammation seen in T2DM. The main aim was to study the effect of hyperinsulinemia on adipokines in individuals with different levels of insulin resistance, glycemia, and obesity. Three groups of sex-matched subjects were studied: young healthy subjects (YS; n = 10; mean age, 26 years; body mass index [BMI], 22 kg/m2), patients with T2DM (DS; n = 10; 61 years; BMI, 27 kg/m2), and age- and BMI-matched controls to DS (CS; n = 10; 60 years; BMI, 27 kg/m2). Plasma concentrations of adipokines were measured during a hyperinsulinemic euglycemic clamp lasting 4 hours. Moreover, insulin-stimulated glucose uptake in isolated adipocytes was analyzed to address adipose tissue insulin sensitivity. Plasma interleukin (IL)-6 increased significantly (P ≤ .01) in all 3 groups during hyperinsulinemia. However, the increase was smaller in both DS (P = .06) and CS (P < .05) compared with YS (∼2.5-fold vs ∼4-fold). A significant increase of plasma tumor necrosis factor (TNF) α was observed only in YS. There were only minor or inconsistent effects on adiponectin, leptin, and high-sensitivity C-reactive protein levels during hyperinsulinemia. Insulin-induced rise in IL-6 correlated negatively to BMI (P = .001), waist to hip ratio (P = .05), and baseline (fasting) insulin (P = .03) and IL-6 (P = .02) levels and positively to insulin-stimulated glucose uptake in isolated adipocytes (P = .07). There was no association with age or insulin sensitivity. In a multivariate analysis, also including T2DM/no T2DM, an independent correlation (inverse) was found only between BMI and fold change of IL-6 (r2 = 0.41 for model, P < .005). Hyperinsulinemia per se can produce an increase in plasma IL-6 and TNFα, and this can potentially contribute to the low-grade inflammation seen in obesity and T2DM. However, obesity seems to attenuate the ability of an acute increase in insulin to further raise circulating levels of IL-6 and possibly TNFα.
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93.
  • Ruge, Toralph, et al. (författare)
  • Effects of hyperinsulinemia on lipoprotein lipase, angiopoietin-like protein 4, and glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 in subjects with and without type 2 diabetes mellitus
  • 2012
  • Ingår i: Metabolism. - : Elsevier BV. - 0026-0495 .- 1532-8600. ; 61:5, s. 652-660
  • Tidskriftsartikel (refereegranskat)abstract
    • Our aims were to compare the systemic effects of insulin on lipoprotein lipase (LPL) in tissues from subjects with different degrees of insulin sensitivity. The effects of insulin on LPL during a 4-hour hyperinsulinemic, euglycemic clamp were studied in skeletal muscle, adipose tissue, and postheparin plasma from young healthy subjects (YS), older subjects with type 2 diabetes mellitus (DS), and older control subjects (CS). In addition, we studied the effects of insulin on the expression of 2 recently recognized candidate genes for control of LPL activity: angiopoietin-like protein 4 (ANGPTL4) and glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1. As an effect of insulin, LPL activity decreased by 20% to 25% in postheparin plasma and increased by 20% to 30% in adipose tissue in all groups. In YS, the levels of ANGPTL4 messenger RNA in adipose tissue decreased 3-fold during the clamp. In contrast, there was no significant change in DS or CS. Regression analysis showed that the ability of insulin to reduce the expression of ANGPTL4 was positively correlated with M-values and inversely correlated with factors linked to the metabolic syndrome. Expression of glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 tended to be higher in YS than in DS or CS, but the expression was not affected by insulin in any of the groups. Our data imply that the insulin-mediated regulation of LPL is not directly linked to the control of glucose turnover by insulin or to ANGPTL4 expression in adipose tissue or plasma. Interestingly, the response of ANGPTL4 expression in adipose tissue to insulin was severely blunted in both DS and CS.
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94.
  • Sarafidis, PA, et al. (författare)
  • The effect of rosiglitazone on novel atherosclerotic risk factors in patients with type 2 diabetes mellitus and hypertension - An open-label observational study
  • 2005
  • Ingår i: Metabolism, Clinical and Experimental. - : Elsevier BV. - 1532-8600. ; 54:9, s. 1236-1242
  • Tidskriftsartikel (refereegranskat)abstract
    • Thiazolidinediones are antidiabetic agents that decrease insulin resistance. Emerging evidence indicates that they present beneficial effects for the vasculature beyond glycemic control. The aim of this open-label observational study was to determine the effect of the thiazolidinedione rosiglitazone on novel cardiovascular risk factors, namely, lipoprotein(a) [Lp(a)], C-reactive protein (CRP), homocysteine, and fibrinogen in patients with type 2 diabetes and hypertension. A total of 40 type 2 diabetic patients already on treatment with 15 mg of glibenclamide daily and with poorly controlled or newly diagnosed hypertension were included in the study. Twenty of them received 4 mg of rosiglitazone daily as added-on therapy, whereas the rest remained on the preexisting antidiabetic treatment for 26 weeks. At baseline and the end of the study, subjects gave blood tests for the determination of Lp(a), CRP, homocysteine, fibrinogen, serum lipids, apolipoprotein (apo) A-I, and apo B. At the end of the study, rosiglitazone treatment was associated with significant reductions in Lp(a) (10.5 [8.9-54.1] to 9.8 [8.0-42.0] mg/dL, P <.05) and CRP levels (0.33 [0.07-2.05] to 0.25 [0.05-1.84] mg/dL, P <.05) vs baseline. Homocysteine levels were not affected but plasma fibrinogen presented a significant increase (303.5 +/- 75.1 to 387.5 +/- 70.4 mg/dL, P <.01) with rosiglitazone. Although no significant changes were observed in the rosiglitazone group for triglycerides, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein (LDL) cholesterol, both apo A-I and apo B presented small significant reductions and the LDL-apo B ratio was significantly increased. None of the above parameters were changed in the control group. In conclusion, rosiglitazone treatment had a beneficial impact on Lp(a), CRP, and LDL particles ' lipid content in type 2 diabetic hypertensive patients but not on homocysteine and fibrinogen. The overall effect of rosiglitazone on cardiovascular risk factors seems positive but must be further evaluated.
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95.
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96.
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97.
  • Semnani-Azad, Zhila, et al. (författare)
  • Plasma metabolite predictors of metabolic syndrome incidence and reversion
  • 2024
  • Ingår i: Metabolism: Clinical and Experimental. - 1532-8600 .- 0026-0495. ; 151
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Metabolic Syndrome (MetS) is a progressive pathophysiological state defined by a cluster of cardiometabolic traits. However, little is known about metabolites that may be predictors of MetS incidence or reversion. Our objective was to identify plasma metabolites associated with MetS incidence or MetS reversion. Methods: The study included 1468 participants without cardiovascular disease (CVD) but at high CVD risk at enrollment from two case-cohort studies nested within the PREvención con DIeta MEDiterránea (PREDIMED) study with baseline metabolomics data. MetS was defined in accordance with the harmonized International Diabetes Federation and the American Heart Association/National Heart, Lung, and Blood Institute criteria, which include meeting 3 or more thresholds for waist circumference, triglyceride, HDL cholesterol, blood pressure, and fasting blood glucose. MetS incidence was defined by not having MetS at baseline but meeting the MetS criteria at a follow-up visit. MetS reversion was defined by MetS at baseline but not meeting MetS criteria at a follow-up visit. Plasma metabolome was profiled by LC-MS. Multivariable-adjusted Cox regression models and elastic net regularized regressions were used to assess the association of 385 annotated metabolites with MetS incidence and MetS reversion after adjusting for potential risk factors. Results: Of the 603 participants without baseline MetS, 298 developed MetS over the median 4.8-year follow-up. Of the 865 participants with baseline MetS, 285 experienced MetS reversion. A total of 103 and 88 individual metabolites were associated with MetS incidence and MetS reversion, respectively, after adjusting for confounders and false discovery rate correction. A metabolomic signature comprised of 77 metabolites was robustly associated with MetS incidence (HR: 1.56 (95 % CI: 1.33–1.83)), and a metabolomic signature of 83 metabolites associated with MetS reversion (HR: 1.44 (95 % CI: 1.25–1.67)), both p < 0.001. The MetS incidence and reversion signatures included several lipids (mainly glycerolipids and glycerophospholipids) and branched-chain amino acids. Conclusion: We identified unique metabolomic signatures, primarily comprised of lipids (including glycolipids and glycerophospholipids) and branched-chain amino acids robustly associated with MetS incidence; and several amino acids and glycerophospholipids associated with MetS reversion. These signatures provide novel insights on potential distinct mechanisms underlying the conditions leading to the incidence or reversion of MetS.
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98.
  • Shakir, Yasameen, et al. (författare)
  • Does the hormonal situation modify lipid effects by lifestyle factors in middle-aged women? Results from a population-based study of Swedish women: the Women's Health in the Lund Area study.
  • 2006
  • Ingår i: Metabolism, Clinical and Experimental. - : Elsevier BV. - 1532-8600. ; 55:8, s. 1060-1066
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of the study was to outline whether the influence by lifestyle factors on serum lipids was modified by the hormonal situation in middle-aged women. Six thousand nine hundred eight women, aged 50 to 59 years, participated in a health assessment program, including a serum lipid profile evaluation. The women were grouped according to their hormonal status into premenopausal (PM) (n = 492), postmenopausal without hormone therapy (HT) (PM0) (n = 3600), and postmenopausal with HT (PMT) (n = 2816). From the PMT group, we analyzed oral (n = 901) and transdermal HT (n = 351) regimens, containing norethisterone acetate and 17β-estradiol. Serum lipids and lipoproteins were determined by conventional methods. Lifestyle factors included smoking and physical activity at leisure time and at work. Multivariate linear regression analysis controlling for age, education, and dietary habits showed that current smoking was positively associated with triglycerides in the PM, PM0, PMT, and oral HT groups. In the PM0, PMT, and oral HT groups, current smoking was positively associated with total cholesterol and low-density lipoprotein and negatively associated with high-density lipoprotein (HDL). Low physical activity at leisure time was positively associated with triglycerides in the PM and PMT groups and negatively associated with HDL in the PM0 and PMT groups. High physical activity at work was positively associated with triglycerides in the PMT group and with total cholesterol in the PM0 group, but negatively associated with HDL in the PMT and transdermal groups. Body mass index was positively associated with triglycerides and negatively with HDL in all the groups regardless of the hormonal situation. The serum lipid profile as influenced by lifestyle factors was modified by the hormonal situation. Compared with the postmenopausal women without HT use, the use of HT contributes to fewer “negative” effects by lifestyle factors on serum lipids.
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99.
  • Siddiqui, Faiza, et al. (författare)
  • Effects of a culturally adapted lifestyle intervention on cardio-metabolic outcomes: a randomized controlled trial in Iraqi immigrants to Sweden at high risk for Type 2 diabetes
  • 2017
  • Ingår i: Metabolism: Clinical and Experimental. - : Elsevier BV. - 0026-0495 .- 1532-8600. ; 66, s. 1-13
  • Tidskriftsartikel (refereegranskat)abstract
    • Background andAims Middle-Eastern immigrants constitute a growing proportion of the Swedish population and are at high risk for Type 2 diabetes. This calls for a more proactive preventive approach for dealing with diabetes risk in this target group. The aim was to test the effect of a culturally adapted lifestyle intervention programme on changes in lifestyle habits and cardio-metabolic outcomes comparing an intervention group with a control group receiving usual care. Methods Citizens of Malmö, Sweden born in Iraq and at high risk for Type 2 diabetes (n=636) were invited. Participation rate was 15.1%. In all, 96 participants were randomized to the intervention group (n=50) or to the control group (n=46). The intervention group was offered seven group sessions addressing healthy diet and physical activity including one cooking class. Changes in body weight, physical activity levels and cardio-metabolic outcomes were evaluated using linear mixed-effects models. Results The mean follow-up time was 3.9 and 3.5months in the intervention and control groups, respectively. The drop-out rate from baseline to the last visit was 30.0% in the intervention group (n=15) and 30.4% in the control group (n=14). The mean insulin sensitivity index increased significantly at follow-up in the intervention group compared to the control group (10.9% per month, p=0.005). The intervention group also reached a significant reduction in body weight (0.4% per month, p=0.004), body mass index (0.4% per month, p=0.004) and LDL-cholesterol (2.1% per month, p=0.036) compared to the control group. In total, 14.3% in the intervention group reached the goal to lose ≥5% of body weight versus none in the control group. Conclusions This culturally adapted lifestyle intervention programme shows a beneficial effect on insulin action, body weight reduction, as well as LDL-cholesterol reduction, in Middle-Eastern immigrants. The programme adapted to resources in primary health care provides tools for improved primary prevention and reduced cardio-metabolic risk in this high-risk group for Type 2 diabetes. © 2016 The Authors
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100.
  • Sjöberg, Sara, 1979, et al. (författare)
  • Circulating soluble CD44 is higher among women than men and is not associated with cardiovascular risk factors or subclinical atherosclerosis
  • 2005
  • Ingår i: Metabolism. - : Elsevier BV. - 0026-0495 .- 1532-8600. ; 54:2, s. 139-41
  • Tidskriftsartikel (refereegranskat)abstract
    • In the present study, the associations between the plasma concentration of soluble CD44 (sCD44), sex, cardiovascular risk factors, and ultrasound-assessed measures of carotid atherosclerosis were examined in 2 groups of 61- and 64-year-old men and women from population-based samples. Women had higher levels of circulating sCD44 than men. There were no associations between sCD44 and cardiovascular risk factors or subclinical atherosclerosis.
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