| 1. |
- Anttila, V., et al.
(författare)
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Direct intramyocardial injection of VEGF mRNA in patients undergoing coronary artery bypass grafting
- 2023
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Ingår i: Molecular Therapy. - : Elsevier BV. - 1525-0016. ; 31:3, s. 866-874
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Tidskriftsartikel (refereegranskat)abstract
- Vascular endothelial growth factor A (VEGF-A) has therapeutic cardiovascular effects, but delivery challenges have impeded clinical development. We report the first clinical study of naked mRNA encoding VEGF-A (AZD8601) injected into the human heart. EPICCURE (ClinicalTrials.gov: NCT03370887) was a randomized, double-blind study of AZD8601 in patients with left ventricular ejection fraction (LVEF) 30%–50% who were undergoing elective coronary artery bypass surgery. Thirty epicardial injections of AZD8601 (total 3 mg) or placebo in citrate-buffered saline were targeted to ischemic but viable myocardial regions mapped using quantitative [15O]-water positron emission tomography. Seven patients received AZD8601 and four received placebo and were followed for 6 months. There were no deaths or treatment-related serious adverse events and no AZD8601-associated infections, immune reactions, or arrhythmias. Exploratory outcomes indicated potential improvement in LVEF, Kansas City Cardiomyopathy Questionnaire scores, and N-terminal pro-B-type natriuretic peptide levels, but the study is limited in size, and significant efficacy conclusions are not possible from the dataset. Naked mRNA without lipid encapsulation may provide a safe delivery platform for introducing genetic material to cardiac muscle, but further studies are needed to confirm efficacy and safety in a larger patient pool. © 2022
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| 2. |
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| 3. |
- Anttila, V., et al.
(författare)
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Synthetic mRNA Encoding VEGF-A in Patients Undergoing Coronary Artery Bypass Grafting: Design of a Phase 2a Clinical Trial
- 2020
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Ingår i: Molecular Therapy-Methods & Clinical Development. - : Elsevier BV. - 2329-0501. ; 18, s. 464-472
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Tidskriftsartikel (refereegranskat)abstract
- Therapeutic angiogenesis may improve outcomes in patients with coronary artery disease undergoing surgical revascularization. Angiogenic factors may promote blood vessel growth and regenerate regions of ischemic but viable myocardium. Previous clinical trials of vascular endothelial growth factor A (VEGF-A) gene therapy with DNA or viral vectors demonstrated safety but not efficacy. AZD8601 is VEGF-A(165) mRNA formulated in biocompatible citrate-buffered saline and optimized for high-efficiency VEGF-A expression with minimal innate immune response. EPICCURE is an ongoing randomized, double-blind, placebo-controlled study of the safety of AZD8601 in patients with moderately decreased left ventricular function (ejection fraction 30% 50%) undergoing elective coronary artery bypass surgery. AZD8601 3 mg, 30 mg, or placebo is administered as 30 epicardial injections in a 10-min extension of cardioplegia. Injections are targeted to ischemic but viable myocardial regions in each patient using quantitative O-15-water positron emission tomography (PET) imaging (stress myocardial blood flow < 2.3 mL/g/min; resting myocardial blood flow > 0.6 mL/g/min). Improvement in regional and global myocardial blood flow quantified with O-15-water PET is an exploratory efficacy outcome, together with echocardiographic, clinical, functional, and biomarker measures. EPICCURE combines high-efficiency delivery with quantitative targeting and follow-up for robust assessment of the safety and exploratory efficacy of VEGF-A mRNA angiogenesis (ClinicalTrials.gov: NCT03370887).
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| 4. |
- Garthwaite, Taru, et al.
(författare)
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Associations of sedentary time, physical activity, and fitness with muscle glucose uptake in adults with metabolic syndrome
- 2022
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Ingår i: Scandinavian Journal of Medicine and Science in Sports. - West Sussex : John Wiley & Sons. - 0905-7188 .- 1600-0838. ; 33:3, s. 353-358
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The objective of the study was to investigate the associations of sedentary time, physical activity, and cardiorespiratory fitness with skeletal muscle glucose uptake (GU). Methods: Sedentary time and physical activity were measured with accelerometers and VO2max with cycle ergometry in 44 sedentary adults with metabolic syndrome. Thigh muscle GU was determined with [18F]FDG-PET imaging. Results: Sedentary time (β = −0.374), standing (β = 0.376), steps (β = 0.351), and VO2max (β = 0.598) were associated with muscle GU when adjusted for sex, age, and accelerometer wear time. Adjustment for body fat-% turned all associations non-significant. Conclusion: Body composition is a more important determinant of muscle GU in this population than sedentary time, physical activity, or fitness. © 2022 The Authors. Scandinavian Journal of Medicine & Science In Sports published by John Wiley & Sons Ltd.
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| 5. |
- Garthwaite, Taru, et al.
(författare)
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Effects of reduced sedentary time on cardiometabolic health in adults with metabolic syndrome : A three-month randomized controlled trial
- 2022
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Ingår i: Journal of Science and Medicine in Sport. - Chatswood : Elsevier Ltd. - 1440-2440 .- 1878-1861. ; 25:7, s. 579-585
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To investigate if reducing sedentary behavior improves cardiometabolic biomarkers in adults with metabolic syndrome. Design: Randomized controlled trial. Methods: Sixty-four sedentary middle-aged adults with metabolic syndrome were randomized into intervention (INT; n = 33) and control (CON; n = 31) groups. INT was guided to limit sedentary behavior by 1 h/day through increased standing and light-intensity physical activity. CON was instructed to maintain usual habits. Sedentary behavior, breaks in sedentary behavior, standing, and physical activity were measured with hip-worn accelerometers for three months. Fasting blood sampling and measurements of anthropometrics, body composition, and blood pressure were performed at baseline and at three months. Linear mixed models were used for statistical analyses. Results: INT reduced sedentary behavior by 50 (95% CI: 24, 73) min/day by increasing light-intensity and moderate-to-vigorous physical activity (19 [8, 30] and 24 [14, 34] min/day, respectively). Standing increased also, but non-significantly (6 [−11, 23] min/day). CON maintained baseline activity levels. Significant intervention effects favoring INT occurred in fasting insulin (INT: 83.4 [68.7, 101.2] vs. CON: 102.0 [83.3, 125.0] pmol/l at three months), insulin resistance (HOMA-IR; 3.2 [2.6, 3.9] vs. 4.0 [3.2, 4.9]), HbA1c (37 [36, 38] vs. 38 [37, 39] mmol/mol), and liver enzyme alanine aminotransferase (28 [24, 33] vs. 33 [28, 38] U/l). Conclusions: Reducing sedentary behavior by 50 min/day and increasing light-intensity and moderate-to-vigorous activity showed benefits in several cardiometabolic biomarkers in adults with metabolic syndrome. Replacing some of the daily sedentary behavior with light-intensity and moderate-to-vigorous physical activity may help in cardiometabolic disease prevention in risk populations. © 2022 The Authors
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| 6. |
- Garthwaite, Taru, et al.
(författare)
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Standing is associated with insulin sensitivity in adults with metabolic syndrome
- 2021
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Ingår i: Journal of Science and Medicine in Sport. - Chatswood : Elsevier. - 1440-2440 .- 1878-1861. ; 24:12, s. 1255-1260
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To determine how components of accelerometer-measured sedentary behavior (SB) and physical activity (PA), and fitness are associated with insulin sensitivity in adults with metabolic syndrome. Design: Cross-sectional. Methods: Target population was middle-aged (40–65 years) sedentary adults with metabolic syndrome. SB, breaks in SB, standing, and PA were measured for four weeks with hip-worn accelerometers. VO2max (ml/min/kg) was measured with maximal cycle ergometry. Insulin sensitivity was determined by hyperinsulinaemic-euglycaemic clamp (M-value) and fasting blood sampling (HOMA-IR, insulin). Multivariable regression was used for analyses. Results: Sixty-four participants (37 women; 58.3 [SD 6.8] years) were included. Participants spent 10.0 (1.0) h sedentary, 1.8 (0.6) h standing, and 2.7 (0.6) h in PA and took 5149 (1825) steps and 29 (8) breaks daily. In sex-, age- and accelerometer wear time-adjusted model SB, standing, steps and VO2max were associated with M-value (β = −0.384; β = 0.400; β = 0.350; β = 0.609, respectively), HOMA-IR (β = 0.420; β = −0.548; β = −0.252; β = −0.449), and insulin (β = 0.433; β = −0.541; β = −0.252; β = −0.453); all p-values < 0.05. Breaks associated only with M-value (β = 0.277). When further adjusted for body fat %, only standing remained significantly associated with HOMA-IR (β = −0.381) and insulin (β = −0.366); significance was maintained even when further adjusted for SB, PA and fitness. Light and moderate-to-vigorous PA were not associated with insulin sensitivity. Conclusions: Standing is associated with insulin sensitivity markers. The association with HOMA-IR and insulin is independent of adiposity, PA, SB and fitness. Further studies are warranted, but these findings encourage replacing sitting with standing for potential improvements in insulin sensitivity in adults at increased type 2 diabetes risk. © 2021 The Authors.
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| 7. |
- Grönman, Maria, et al.
(författare)
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Assessment of myocardial viability with [15O]water PET : A validation study in experimental myocardial infarction
- 2021
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Ingår i: Journal of Nuclear Cardiology. - : Springer Nature. - 1071-3581 .- 1532-6551. ; 28:4, s. 1271-1280
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Assessment of myocardial viability is often needed in patients with chest pain and reduced ejection fraction. We evaluated the performance of reduced resting MBF, perfusable tissue fraction (PTF), and perfusable tissue index (PTI) in the assessment of myocardial viability in a pig model of myocardial infarction (MI).METHODS AND RESULTS: Pigs underwent resting [15O]water PET perfusion study 12 weeks after surgical (n = 16) or 2 weeks after catheter-based (n = 4) occlusion of the proximal left anterior descending coronary artery. MBF, PTF, and PTI were compared with volume fraction of MI in matched segments as assessed by triphenyl tetrazolium chloride staining of LV slices. MBF and PTF were lower in infarcted than non-infarcted segments. Segmental analysis of MBF showed similar area under the curve (AUC) of 0.85, 0.86, and 0.90 with relative MBF, PTF, and PTI for the detection of viable myocardium defined as infarct volume fraction of < 75%. Cut-off values of relative MBF of ≥ 67% and PTF of ≥ 66% resulted in accuracies of 90% and 81%, respectively.CONCLUSIONS: Our results indicate that resting MBF, PTF, and PTI based on [15O]water PET perfusion imaging are useful for the assessment of myocardial viability.
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| 8. |
- Haapala, Eero A., et al.
(författare)
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Association between cardiorespiratory fitness and metabolic health in overweight and obese adults
- 2022
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Ingår i: Journal of Sports Medicine and Physical Fitness. - Turin : Edizioni Minerva Medica. - 0022-4707 .- 1827-1928. ; 62:11, s. 1526-1533
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cardiorespiratory fitness (CRF) has been inversely associated with insulin resistance and clustering of cardiometabolic risk factors among overweight and obese individuals. However, most previous studies have scaled CRF by body mass (BM) possibly inflating the association between CRF and cardiometabolic health. We investigated the associations of peak oxygen uptake (V?O2peak) and peak power output (Wpeak) scaled either by BM-1, fat free mass (FFM-1), or by allometric methods with individual cardiometabolic risk factors and clustering of cardiometabolic risk factors in 55 overweight or obese adults with metabolic syndrome. METHODS: VO2peak and Wpeak were assessed by a maximal cycle ergometer exercise test. FFM was measured by air displacement plethysmo- graph and glucose, insulin, HbA1c, triglycerides, and total, LDL, and HDL cholesterol from fasting blood samples. HOMA-IR and metabolic syndrome score (MetS) were computed. RESULTS: VO2peak and Wpeak scaled by BM-1 were inversely associated with insulin (β=-0.404 to -0.372, 95% CI: -0.704 to -0.048), HOMAIR (β=-0.442 to -0.440, 95% CI: -0.762 to -0.117), and MetS (β=-0.474 to -0.463, 95% CI: -0.798 to -0.127). Other measures of CRF were not associated with cardiometabolic risk factors. CONCLUSIONS: Our results suggest that using BM-1 as a scaling factor confounds the associations between CRF and cardiometabolic risk in overweight/obese adults with the metabolic syndrome. © 2022 EDIZIONI MINERVA MEDICA.
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| 9. |
- Kero, Tanja, et al.
(författare)
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Quantitative myocardial perfusion response to adenosine and regadenoson in patients with suspected coronary artery disease
- 2022
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Ingår i: Journal of Nuclear Cardiology. - : Springer Science and Business Media LLC. - 1071-3581 .- 1532-6551. ; 29:1, s. 24-36
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The aim of the present study was to compare the quantitative flow responses of regadenoson against adenosine using cardiac 15O-water PET imaging in patients with suspected or known coronary artery disease (CAD).METHODS: Hyperemic myocardial blood flow (MBF) after adenosine and regadenoson was compared using correlation and Bland-Altman analysis in 21 patients who underwent rest and adenosine 15O-water PET scans followed by rest and regadenoson 15O-water PET scans.RESULTS: Global mean (± SD) MBF values at rest and stress were 0.92 ± 0.27 and 2.68 ± 0.80 mL·g·min for the adenosine study and 0.95 ± 0.29 and 2.76 ± 0.79 mL·g·min for the regadenoson study (P = 0.55 and P = 0.49). The correlations between global and regional adenosine- and regadenoson-based stress MBF were strong (r = 0.80 and r = 0.77). The biases were small for both global and regional MBF comparisons (0.08 and 0.09 mL·min·g), but the limits of agreement were wide for stress MBF.CONCLUSION: The correlation between regadenoson- and adenosine-induced hyperemic MBF was strong but the agreement was only moderate indicating that established cut-off values for 150-water PET should be used cautiously if using regadenoson as vasodilator.
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| 10. |
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| 11. |
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| 12. |
- Koivula, Tiia, et al.
(författare)
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Cross-Sectional Associations of Body Adiposity, Sedentary Behavior, and Physical Activity with Hemoglobin and White Blood Cell Count
- 2022
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Ingår i: International Journal of Environmental Research and Public Health. - Basel : MDPI. - 1661-7827 .- 1660-4601. ; 19:21
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Tidskriftsartikel (refereegranskat)abstract
- Background: This study examined whether hemoglobin (Hb) and white blood cell count (WBC) associate with body adiposity and other cardiometabolic risk factors, as well as accelerometer-measured sedentary behavior (SB) and physical activity (PA), when adjusted for body mass index (BMI). Methods: The cross-sectional analysis included 144 participants (42 men) with a mean age of 57.0 years and a mean BMI of 31.7 kg/m2. SB and standing time, breaks in sedentary time and PA were measured during four consecutive weeks with hip-worn accelerometers. A fasting blood sample was collected from each participant during the 4-week measurement period and analyzed using Sysmex XN and Cobas 8000 c702 analyzers. Associations of WBC, Hb and other red blood cell markers with cardiometabolic risk factors and physical activity were examined by Pearson’s partial correlation coefficient test and with linear mixed regression models. Results: In sex- and age-adjusted correlation analyses both BMI and waist circumference correlated positively with Hb, WBC, red blood cell count (RBC), and hematocrit. Hb was also positively correlated with systolic blood pressure, insulin resistance scores, liver enzymes, LDL, and triglyceride levels. Sedentary time correlated positively with WBC, whereas standing time correlated negatively with WBC. Lying time correlated positively with WBC, RBC, hematocrit, and Hb. Regarding SB and PA measures, only the association between lying time and RBC remained significant after adjustment for the BMI. Conclusion: We conclude that body adiposity, rather than components of SB or PA, associates with Hb levels and WBC, which cluster with general metabolic derangement. © 2022 by the authors.
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| 13. |
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| 14. |
- Laine, Saara, et al.
(författare)
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Body Adiposity, But Not Elements of Objectively Measured Sedentary Behavior or Physical Activity, Is Associated With Circulating Liver Enzymes in Adults With Overweight and Obesity
- 2021
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Ingår i: Frontiers in Endocrinology. - Lausanne : Frontiers Media S.A.. - 1664-2392. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Objective: We studied the associations between accelerometer-measured sedentary behavior (SB) and habitual physical activity (PA) as well as markers of body adiposity and other cardiometabolic risk factors with liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyltransferase (GGT). Methods: A total of 144 middle-aged adults (mean age 57 (SD 6.5) years) with overweight or obesity (mean body mass index [BMI] 31.8 [SD 3.9] kg/m2) participated. Different components of SB (sitting, lying) and PA (standing, breaks in SB, daily steps, light PA, moderate-to-vigorous PA and total PA) were measured with validated hip-worn accelerometers for four consecutive weeks (mean 25 days, [SD 4]). Fasting venous blood samples were analysed using standard assays. The associations were examined with Pearson’s partial correlation coefficient test and linear mixed model. Results: Among 102 women and 42 men accelerometer measured SB or the elements of PA were not associated with circulating liver enzymes. When adjusted for age and sex, liver enzymes correlated positively with BMI and waist circumference (WC) (ALT r=0.34, p<0.0001, r=0.41, < 0.0001, AST r=0.17, p=0.049, r=0.26, p=0.002, GGT r=0.29, p=0.0005, r=0.32, p < 0.0001, respectively). SB proportion associated positively with BMI (r=0.21, p=0.008) and WC (r=0.27, p=0.001). Components of PA associated negatively with BMI (MVPA r=-0.23, p=0.005, daily steps r=-0.30, p<0.0001 and breaks in sedentary time r=-0.32, p<0.0001), as well as with WC (breaks in SB r=-0.35, p<0.0001, MVPA r=-0.26, p=0.002, daily steps r=-0.31, p<0.0001, standing time r=-0.27, p=0.001). Liver enzymes associated positively with common cardiometabolic markers such as resting heart rate (ALT; β=0.17, p=0.03, AST; β=0.25, p=0.002, GGT; β=0.23, p=0.004) and systolic/diastolic blood pressure (ALT β=0.20, p=0.01, β=0.22, p=0.005, AST (only diastolic) β=0.23, p=0.006, GGT β=0.19, p=0.02, = 0.23, p=0.004, respectively), fasting insulin (ALT β=0.41, p<0.0001, AST β=0.36, p=0.0003, GGT β=0.20, p=0.04) and insulin resistance index (ALT β=0.42, p<0.0001, AST β=0.36, p=0.0003, GGT β=0.21, p=0.03), even after adjustment with BMI. Conclusions: Liver enzymes correlate with body adiposity and appear to cluster with other common cardiometabolic risk factors, even independently of body adiposity. SB and PA appear not to be essential in modulating the levels of circulating liver enzymes. © Copyright © 2021 Laine, Sjöros, Vähä-Ypyä, Garthwaite, Löyttyniemi, Sievänen, Vasankari, Knuuti and Heinonen.
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| 15. |
- Laine, Saara, et al.
(författare)
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Relationship between liver fat content and lifestyle factors in adults with metabolic syndrome
- 2022
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Ingår i: Scientific Reports. - London : Nature Publishing Group. - 2045-2322. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate the associations between liver fat content (LFC), sedentary behaviour (SB), physical activity (PA), fitness, diet, body composition, and cardiometabolic risk factors in adults with metabolic syndrome. A total of 44 sedentary adults (mean age 58 [SD 7] years; 25 women) with overweight or obesity participated. LFC was assessed with magnetic resonance spectroscopy and imaging, SB and PA with hip-worn accelerometers (26 [SD 3] days), fitness by maximal bicycle ergometry, body composition by air displacement plethysmography and nutrient intake by 4-day food diaries. LFC was not independently associated with SB, PA or fitness. Adjusted for sex and age, LFC was associated with body fat%, body mass index, waist circumference, triglycerides, alanine aminotransferase, and with insulin resistance markers. There was and inverse association between LFC and daily protein intake, which persisted after further adjusment with body fat%. LFC is positively associated with body adiposity and cardiometabolic risk factors, and inversely with daily protein intake. SB, habitual PA or fitness are not independent modulators of LFC. However, as PA is an essential component of healthy lifestyle, it may contribute to liver health indirectly through its effects on body composition in adults with metabolic syndrome. © 2022, The Author(s).
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| 16. |
- Norha, Jooa, et al.
(författare)
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Effects of reducing sedentary behavior on cardiorespiratory fitness in adults with metabolic syndrome : A 6-month RCT
- 2023
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Ingår i: Scandinavian Journal of Medicine and Science in Sports. - Chichester : Wiley-Blackwell Publishing Inc.. - 0905-7188 .- 1600-0838. ; 33:8, s. 1452-1461
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Tidskriftsartikel (refereegranskat)abstract
- Introduction:Poor cardiorespiratory fitness (CRF) is associated with adverse health outcomes. Previous observational and cross-sectional studies have suggested that reducing sedentary behavior (SB) might improve CRF. Therefore, we investigated the effects of a 6-month intervention of reducing SB on CRF in 64 sedentary inactive adults with metabolic syndrome in a non-blind randomized controlled trial.Materials and Methods:In the intervention group (INT, n = 33), the aim was to reduce SB by 1 h/day for 6 months without increasing exercise training. Control group (CON, n = 31) was instructed to maintain their habitual SB and physical activity. Maximal oxygen uptake (VO2max) was measured by maximal graded bicycle ergometer test with respiratory gas measurements. Physical activity and SB were measured during the whole intervention using accelerometers.Results:Reduction in SB did not improve VO2max statistically significantly (group × time p > 0.05). Maximal absolute power output (Wmax) did not improve significantly but increased in INT compared to CON when scaled to fat free mass (FFM) (at 6 months INT 1.54 [95% CI: 1.41, 1.67] vs. CON 1.45 [1.32, 1.59] Wmax/kgFFM, p = 0.036). Finally, the changes in daily step count correlated positively with the changes in VO2max scaled to body mass and FFM (r = 0.31 and 0.30, respectively, p < 0.05).Discussion:Reducing SB without adding exercise training does not seem to improve VO2max in adults with metabolic syndrome. However, succeeding in increasing daily step count may increase VO2max. © 2023 The Authors. Scandinavian Journal of Medicine & Science In Sports published by John Wiley & Sons Ltd.
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| 17. |
- Norha, Jooa, et al.
(författare)
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Standing time and daily proportion of sedentary time are associated with pain-related disability in a one month accelerometer measurement in adults with overweight or obesity
- 2022
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Ingår i: Scandinavian Journal of Pain. - Berlin : Walter de Gruyter. - 1877-8860 .- 1877-8879. ; 22:2, s. 317-324
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Tidskriftsartikel (refereegranskat)abstract
- The association between the subjective experience of pain-related disability (PRD) and device-measured physical activity (PA) and sedentary behavior (SB) in overweight and obese adults is not well known. The aim of this study was to investigate the associations of pain markers with accelerometer-measured SB duration and different intensities of PA among physically inactive middle-aged adults with overweight or obesity. This cross-sectional analysis included 72 subjects (27 men) with mean age of 57.9 (SD 6.7) years and mean BMI of 31.6 (SD 4.1) kg/m2. SB and standing time (ST), breaks in sedentary time, light physical activity (LPA) and moderate-to-vigorous physical activity (MVPA) were measured for four consecutive weeks (mean 25 days, SD 4) with a hip-worn triaxial accelerometer. Headache, musculoskeletal pain, back pain, and PRD were assessed by visual analog scales (VAS) and using the Oswestry disability index (ODI). RAND-36 questionnaire was applied to assess health-related quality of life. The associations were studied by linear models. ST was positively and SB proportion was negatively associated with PRD when adjusted for age, sex, BMI, accelerometry duration, MVPA, pain medication use, and general health perceptions assessed by RAND-36. No associations were found between ST and back pain. SB or different PA intensities were not associated with pain experience at specific sites. Longer daily ST, but not LPA or MVPA is associated with higher level of PRD. Correspondingly, higher proportion of SB is associated with lower level of PRD. This suggests that individuals with PRD prefer to stand, possibly to cope with pain. These results may highlight the importance of habitual standing behaviors in coping with experienced PRD in adults with overweight or obesity. © 2021 Walter de Gruyter GmbH, Berlin/Boston.
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| 18. |
- Sjöros, Tanja, et al.
(författare)
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Both sedentary time and physical activity are associated with cardiometabolic health in overweight adults in a 1 month accelerometer measurement
- 2020
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Ingår i: Scientific Reports. - London : Nature Publishing Group. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to examine the associations of cardiometabolic health markers with device-measured sedentary behavior (SB) duration and different intensities of physical activity (PA) among overweight working-aged adults with low self-reported PA levels. This cross-sectional analysis included 144 subjects (42 men) with mean age of 57 (SD 6.5) years and mean BMI of 31.7 (SD 4) kg/m2. SB and standing time, breaks in sedentary time, light PA (LPA) and moderate-to-vigorous PA (MVPA) were measured for 4 consecutive weeks (mean 25 days, SD 4) with hip-worn accelerometers. Fasting plasma glucose, insulin, HbA1c, triglycerides and total cholesterol, HDL and LDL were measured from venous blood samples. HOMA-IR index was calculated as a surrogate of insulin resistance. The associations were examined using linear models. LPA, MVPA, and daily steps associated with better insulin sensitivity and favorable plasma lipid profile, when adjusted for age, sex and BMI, whereas greater proportion of SB associated with insulin resistance and unfavorable lipid profile. As all PA intensities associated with better cardiometabolic health, the total daily duration of PA may be more relevant than intensity in maintaining metabolic health in overweight adults, if the current guidelines for PA are not met.Trial Registration: ClinicalTrials.gov NCT03101228, registered 05/04/2017, https://clinicaltrials.gov/show/NCT03101228 .
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| 19. |
- Sjöros, Tanja, et al.
(författare)
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Influence of the Duration and Timing of Data Collection on Accelerometer-Measured Physical Activity, Sedentary Time and Associated Insulin Resistance
- 2021
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Ingår i: International Journal of Environmental Research and Public Health. - Basel : MDPI AG. - 1661-7827 .- 1660-4601. ; 18:9
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Tidskriftsartikel (refereegranskat)abstract
- Accelerometry is a commonly used method to determine physical activity in clinical studies, but the duration and timing of measurement have seldom been addressed. We aimed to evaluate possible changes in the measured outcomes and associations with insulin resistance during four weeks of accelerometry data collection. This study included 143 participants (median age of 59 (IQR9) years; mean BMI of 30.7 (SD4) kg/m2; 41 men). Sedentary and standing time, breaks in sedentary time, and different intensities of physical activity were measured with hip-worn accelerometers. Differences in the accelerometer-based results between weeks 1, 2, 3 and 4 were analyzed by mixed models, differences during winter and summer by two-way ANOVA, and the associations between insulin resistance and cumulative means of accelerometer results during weeks 1 to 4 by linear models. Mean accelerometry duration was 24 (SD3) days. Sedentary time decreased after three weeks of measurement. More physical activity was measured during summer compared to winter. The associations between insulin resistance and sedentary behavior and light physical activity were non-significant after the first week of measurement, but the associations turned significant in two to three weeks. If the purpose of data collection is to reveal associations between accelerometer-measured outcomes and tenuous health outcomes, such as insulin sensitivity, data collection for at least three weeks may be needed © 2021 by the author. Licensee MDPI, Basel, Switzerland.
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| 20. |
- Sjöros, Tanja, et al.
(författare)
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Reducing Sedentary Time and Whole-Body Insulin Sensitivity in Metabolic Syndrome : A 6-Month Randomized Controlled Trial
- 2023
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Ingår i: Medicine & Science in Sports & Exercise. - Philadelphia, PA : Lippincott Williams & Wilkins. - 0195-9131 .- 1530-0315. ; 55:3, s. 342-353
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: This study aimed to investigate whether a reduction in daily sedentary behavior (SB) improves insulin sensitivity in adults with metabolic syndrome in 6 months, without adding intentional exercise training.Methods: Sixty-four sedentary inactive middle-age adults with overweight and metabolic syndrome (mean (SD) age, 58 (7) yr; mean (SD) body mass index, 31.6 (4.3) kg.m(-2); 27 men) were randomized into intervention and control groups. The 6-month individualized behavioral intervention supported by an interactive accelerometer and a mobile application aimed at reducing daily SB by 1 h compared with baseline. Insulin sensitivity by hyperinsulinemic euglycemic clamp, body composition by air displacement plethysmography, and fasting blood samples were analyzed before and after the intervention. SB and physical activity were measured with hip-worn accelerometers throughout the intervention.Results: SB decreased by 40 (95% confidence interval, 17-65) min.d(-1), and moderate-to-vigorous physical activity increased by 20 (95% confidence interval, 11-28) min.d(-1) on average in the intervention group with no significant changes in these outcomes in the control group. After 6 months, fasting plasma insulin decreased (similar to 1 mU.L-1) in the intervention group compared with the control group (time-group, P = 0.0081), but insulin sensitivity did not change in either group. The changes in body mass or adiposity did not differ between groups. Among all participants, the changes in SB and body mass correlated inversely with the change in insulin sensitivity (r = -0.31, -0.44; P = 0.025, 0.0005, respectively).Conclusions: An intervention aimed at reducing daily SB resulted in slightly decreased fasting insulin, but had no effects on insulin sensitivity or body adiposity. However, as the change in insulin sensitivity associated with the changes in SB and body mass, multifaceted interventions targeting to weight loss are likely to be beneficial in improving whole-body insulin sensitivity. © Lippincott Williams & Wilkins.
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| 21. |
- Sjöros, Tanja, et al.
(författare)
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The effects of a 6-month intervention aimed to reduce sedentary time on skeletal muscle insulin sensitivity : a randomized controlled trial
- 2023
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Ingår i: American Journal of Physiology. Endocrinology and Metabolism. - Rockville, MD : American Physiological Society. - 0193-1849 .- 1522-1555. ; 325:2, s. E152-E162
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Tidskriftsartikel (refereegranskat)abstract
- Sedentary behavior (SB) and physical inactivity associate with impaired insulin sensitivity. We investigated whether an intervention aimed at a 1-h reduction in daily SB during 6 mo would improve insulin sensitivity in the weight-bearing thigh muscles. Forty-four sedentary inactive adults [mean age 58 (SD 7) yr; 43% men] with metabolic syndrome were randomized into intervention and control groups. The individualized behavioral intervention was supported by an interactive accelerometer and a mobile application. SB, measured with hip-worn accelerometers in 6-s intervals throughout the 6-mo intervention, decreased by 51 (95% CI 22-80) min/day and physical activity (PA) increased by 37 (95% CI 18-55) min/day in the intervention group with nonsignificant changes in these outcomes in the control group. Insulin sensitivity in the whole body and in the quadriceps femoris and hamstring muscles, measured with hyperinsulinemic-euglycemic clamp combined with [18F]fluoro-deoxy-glucose PET, did not significantly change during the intervention in either group. However, the changes in hamstring and whole body insulin sensitivity correlated inversely with the change in SB and positively with the changes in moderate-to-vigorous PA and daily steps. In conclusion, these results suggest that the more the participants were able to reduce their SB, the more their individual insulin sensitivity increased in the whole body and in the hamstring muscles but not in quadriceps femoris. However, according to our primary randomized controlled trial results, this kind of behavioral interventions targeted to reduce sedentariness may not be effective in increasing skeletal muscle and whole body insulin sensitivity in people with metabolic syndrome at the population level.NEW & NOTEWORTHY Aiming to reduce daily SB by 1 h/day had no impact on skeletal muscle insulin sensitivity in the weight-bearing thigh muscles. However, successfully reducing SB may increase insulin sensitivity in the postural hamstring muscles. This emphasizes the importance of both reducing SB and increasing moderate-to-vigorous physical activity to improve insulin sensitivity in functionally different muscles of the body and thus induce a more comprehensive change in insulin sensitivity in the whole body.
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| 22. |
- Smiseth, Otto A, et al.
(författare)
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Multimodality imaging in patients with heart failure and preserved ejection fraction : an expert consensus document of the European Association of Cardiovascular Imaging.
- 2022
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Ingår i: European Heart Journal Cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2404 .- 2047-2412. ; 23:2, s. e34-e61
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Tidskriftsartikel (refereegranskat)abstract
- Nearly half of all patients with heart failure (HF) have a normal left ventricular (LV) ejection fraction (EF) and the condition is termed heart failure with preserved ejection fraction (HFpEF). It is assumed that in these patients HF is due primarily to LV diastolic dysfunction. The prognosis in HFpEF is almost as severe as in HF with reduced EF (HFrEF). In contrast to HFrEF where drugs and devices are proven to reduce mortality, in HFpEF there has been limited therapy available with documented effects on prognosis. This may reflect that HFpEF encompasses a wide range of different pathological processes, which multimodality imaging is well placed to differentiate. Progress in developing therapies for HFpEF has been hampered by a lack of uniform diagnostic criteria. The present expert consensus document from the European Association of Cardiovascular Imaging (EACVI) provides recommendations regarding how to determine elevated LV filling pressure in the setting of suspected HFpEF and how to use multimodality imaging to determine specific aetiologies in patients with HFpEF.
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| 23. |
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| 24. |
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| 25. |
- Virta, Jenni, et al.
(författare)
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Effects of dipeptidyl peptidase 4 inhibition on inflammation in atherosclerosis : A 18F-fluorodeoxyglucose study of a mouse model of atherosclerosis and type 2 diabetes
- 2020
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Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 305, s. 64-72
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Dipeptidyl peptidase 4 (DPP-4) inhibitors have anti-inflammatory and atheroprotective effects. We evaluated the effects of the DPP-4 inhibitor linagliptin on atherosclerotic plaque and hepatic inflammation using histology and 2-deoxy-2-[18F]-fluoro-D-glucose (18F-FDG), a positron emission tomography tracer of inflammation, in a mouse model of hypercholesterolemia and type 2 diabetes. Methods: Igf2/Ldlr−/−Apob100/100 mice were fed a high-fat diet (HFD) for 8 weeks and then randomly allocated to receive HFD (n = 14), or HFD with added linagliptin (n = 15) for additional 12 weeks. Five mice fed a chow diet were studied as an additional control. At the end of the study, glucose tolerance, aortic and liver uptake of 18F-FDG, and histology were studied. Results: Mice in linagliptin and HFD groups had similar fasting glucose concentrations, but linagliptin improved glucose tolerance. Aortas of linagliptin and HFD groups showed advanced atherosclerotic plaques with no difference in the mean intima-to-media ratio or number of macrophages in the plaques. Autoradiography showed similar 18F-FDG uptake by atherosclerotic plaques in linagliptin and HFD groups (plaque-to-wall ratio: 1.7 ± 0.25 vs. 1.6 ± 0.21; p = 0.24). In the liver, linagliptin reduced the histologic inflammation score but had no effect on 18F-FDG uptake. Compared with chow diet, uptake of 18F-FDG was similar in the aorta, but higher in the liver after HFD. Conclusions: Linagliptin therapy improved glucose tolerance and reduced hepatic inflammation but had no effect on plaque burden or atherosclerotic inflammation, as determined by histology and 18F-FDG uptake, in atherosclerotic mice with type 2 diabetes.
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| 26. |
- Virta, J, et al.
(författare)
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Impact of metabolic substrate modification on myocardial efficiency in a rat model of obesity and diabetes
- 2022
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Ingår i: European Heart Journal, Supplement. - : Oxford University Press (OUP). - 1520-765X .- 0195-668X .- 1522-9645. ; 43:2, s. 3076-3076
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Konferensbidrag (refereegranskat)abstract
- BackgroundCongenic leptin receptor deficient rat generated by introgression of the Koletsky leptin receptor mutation into BioBreeding Diabetes Resistant rat (BBDR.lepr−/−) is a novel animal model combining obesity, systemic insulin resistance and diabetes. Systemic insulin resistance is associated with reduced myocardial glucose utilization, but its effect on myocardial external efficiency, i.e. the ability of the myocardium to convert energy into external stroke work, remains uncertain.PurposeTo characterize cardiac energy metabolism and function in BBDR.lepr−/− rats and to study the effect of dipeptidyl peptidase 4 (DPP-4) inhibitor linagliptin in this model.MethodsCardiac phenotype was evaluated in six-month-old male BBDR.lepr−/− rats (n=11) and age-matched male non-diabetic lean control littermates (BBDR.lepr+/− or BBDR.lepr+/+ rats, n=14). Of these, 7 BBDR.lepr−/− rats and 6 controls underwent cardiac ultrasound, 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT), and [11C]acetate PET in order to evaluate cardiac structure and function as well as glucose and oxidative metabolism. In the remaining rats, fatty acid metabolism was evaluated by [18F]fluorothia-6-heptadecanoic acid ([18F]FTHA) PET/CT. In the linagliptin intervention study, 25 BBDR.lepr−/− male rats were randomly divided into control group (n=11) that received regular chow diet and linagliptin group (n=14) that received linagliptin (10mg/kg/d) mixed in the chow diet for three months. After the intervention, the rats underwent cardiac ultrasound, [18F]FDG PET/CT, and [11C]acetate PET.ResultsCompared with controls, BBDR.lepr−/− rats showed increased left ventricle (LV) mass (∼40%, p>0.001) and higher systolic blood pressure (∼10%, p=0.02). However, fractional shortening and cardiac output were similar in both groups. Myocardial fractional uptake rate of glucose measured with [18F]FDG PET was significantly reduced (∼86%, p=0.004) (Fig. 1A, E), whereas myocardial fatty acid uptake measured by [18F]FTHA PET was not significantly increased (free fatty acid (FFA) corrected standardized uptake value (SUV) ∼21%, p=0.54) (Fig. 1B) in BBDR.lepr−/− compared to controls. Myocardial oxygen consumption assessed by [11C]acetate PET was similar in both groups (Fig. 1C, E), but LV work per gram of myocardium was reduced (∼28%, p=0.001) resulting in reduced myocardial external efficiency (∼21%, p=0.03) (Fig. 1D) in BBDR.lepr−/− compared to controls. Treatment with linagliptin significantly enhanced myocardial fractional uptake rate of glucose (∼166%, p=0.006) (Fig. 2A, C), but had no effect on efficiency of cardiac work (Fig. 2B).ConclusionsObese and diabetic BBDR.lepr−/− rats demonstrate LV hypertrophy and markedly reduced myocardial glucose utilization associated with impaired myocardial external efficiency despite normal LV systolic function. Enhancement of myocardial glucose uptake by linagliptin did not improve efficiency of cardiac work.Funding AcknowledgementType of funding sources: Public grant(s) – EU funding. Main funding source(s): IMI-SUMMIT
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