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Effects of reduced sedentary time on resting, exercise and post-exercise blood pressure in inactive adults with metabolic syndrome - a six-month exploratory RCT.
Norha, J, Sjöros, T, Garthwaite, T, Laine, S, Saarenhovi, M, Kallio, P, Laitinen, K, Houttu, N, Vähä-Ypyä, H, Sievänen, H, et al
Journal of human hypertension. 2024;(4):314-321
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Abstract
Evidence on the long-term effects of reducing sedentary behaviour (SB) on blood pressure (BP) is scarce. Therefore, we performed a sub-analysis of the BP effects of a six-month intervention that aimed at reducing SB by 1 h/day and replacing it with non-exercise activities. Sixty-four physically inactive and sedentary adults with metabolic syndrome (58% female, 58 [SD 7] years, BP 143/88 [16/9] mmHg, SB 10 [1] h/day) were randomised into intervention (INT, n = 33) and control (CON, n = 31) groups. Resting BP and BP at each stage during and after a graded maximal bicycle ergometer test were measured before and after the intervention. SB, standing, moderate-to-vigorous physical activity (MVPA), and light physical activity (LPA) were measured in six-second intervals at baseline and during the whole six-month intervention using hip-worn accelerometers. The analyses were adjusted for BP medication status. The intervention resulted in a 40 min/day reduction in SB and concomitant 20 min/day increase in MVPA. Resting systolic BP was lower in the CON group before and after the intervention. No group x time interactions were observed in resting BP or BP during exercise at submaximal or maximal intensities, or during recovery. The changes in LPA and MVPA were inversely correlated with the changes in BP during light-to-moderate intensity exercise. An intervention that resulted in a 40 min/day reduction in SB for six months was not sufficient at influencing BP at rest, during or after exercise in adults with metabolic syndrome. However, successfully increasing LPA or MVPA might lower BP during light-to-moderate-intensity activities.
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Characterising the use, users and effects of a health app supporting lifestyle changes in pregnant women.
Koivuniemi, E, Raats, MM, Ollila, H, Löyttyniemi, E, Laitinen, K
The British journal of nutrition. 2023;(3):433-445
Abstract
The study objective was to (1) compare, through a randomised pilot intervention study, the effects of a standard health app and an enhanced health app, with evidence-based information regarding healthy lifestyle, on gestational weight gain, diet quality and physical activity in pregnant women. The sub-objectives were to (2) characterise app use and users among pregnant women and to (3) compare, in the overall sample regardless of the intervention, whether the frequency of the health app use has an effect on the change in gestational weight, diet quality and physical activity. Women recruited through social media announcements (n 1038) were asked to record their lifestyle habits in the app from early pregnancy to delivery. Self-reported weight, diet quality and physical activity were assessed in early and late pregnancy with validated online questionnaires. No benefits of the enhanced app use were shown on the lifestyle habits. Nevertheless, frequent app users (use ≥ 4·7 weeks) in the enhanced app group had a higher physical activity level in late pregnancy compared with those in the standard app group. Overall, extensive variation was found in the number of recordings (median 59, interquartile range 19-294) and duration of app use (median 4·7, interquartile range 1·1-15·6 weeks). Frequent app users had higher education level, underweight/normal weight, better diet quality and were non-smokers, married and primipara more likely than occasional app users/non-users. Physical activity among app users decreased less compared with non-users over the pregnancy course, indicating that app use could motivate to maintain physical activity during pregnancy.
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Reducing Sedentary Time and Whole-Body Insulin Sensitivity in Metabolic Syndrome: A 6-Month Randomized Controlled Trial.
Sjöros, T, Laine, S, Garthwaite, T, Vähä-Ypyä, H, Löyttyniemi, E, Koivumäki, M, Houttu, N, Laitinen, K, Kalliokoski, KK, Sievänen, H, et al
Medicine and science in sports and exercise. 2023;(3):342-353
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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 (~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.
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Effects of reducing sedentary behavior on cardiorespiratory fitness in adults with metabolic syndrome: A 6-month RCT.
Norha, J, Sjöros, T, Garthwaite, T, Laine, S, Saarenhovi, M, Kallio, P, Laitinen, K, Houttu, N, Vähä-Ypyä, H, Sievänen, H, et al
Scandinavian journal of medicine & science in sports. 2023;(8):1452-1461
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 .
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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.
Sjöros, T, Laine, S, Garthwaite, T, Vähä-Ypyä, H, Koivumäki, M, Eskola, O, Löyttyniemi, E, Houttu, N, Laitinen, K, Kalliokoski, KK, et al
American journal of physiology. Endocrinology and metabolism. 2023;(2):E152-E162
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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Effects of reduced sedentary time on cardiometabolic health in adults with metabolic syndrome: A three-month randomized controlled trial.
Garthwaite, T, Sjöros, T, Laine, S, Vähä-Ypyä, H, Löyttyniemi, E, Sievänen, H, Houttu, N, Laitinen, K, Kalliokoski, K, Vasankari, T, et al
Journal of science and medicine in sport. 2022;(7):579-585
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.
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Bioactive glass granules versus standard autologous and allogeneic bone grafts: a randomized trial of 49 adult bone tumor patients with a 10-year follow-up.
Aro, HT, Välimäki, VV, Strandberg, N, Lankinen, P, Löyttyniemi, E, Saunavaara, V, Seppänen, M
Acta orthopaedica. 2022;:519-527
Abstract
BACKGROUND AND PURPOSE As a synthetic bone void filler, bioactive glasses (BGs) may enhance angiogenesis and osteogenesis. In this randomized trial, we compared the clinical efficacy of BG granules and standard bone grafts in patients undergoing surgery for benign bone tumors. PATIENTS AND METHODS 49 recruited patients were randomized to receive BG granules or undergo conventional bone grafting to fill defects following tumor removal. As the standard of care, small-sized defects were filled with autologous graft, and large-sized defects were filled with allogeneic graft. The primary endpoint was treatment success at 1 year, defined by no reoperation, no tumor recurrence, and no device-related adverse events. Secondary endpoints included patient-reported outcomes (Rand-36 and pain scores) and quantitative assessment of blood flow and metabolic activity by means of 18F-fluoride PET/CT imaging. As an off-trial group, 15 children and adolescents (age < 18 years) underwent tumor removal and BG-filling, without randomization. RESULTS At 1-year, 21 of 25 BG-treated patients (risk estimate 0.84, 95% confidence interval [CI] 0.70-0.98) and 20 of 24 patients in the standard of care group (0.83, CI 0.68-0.98) met the criteria for treatment success. The groups had similar Rand-36 scores. In patients with small defects, BG filling was associated with shorter operative time and less postoperative pain at 1 month. In patients with large defects, blood flow was similar, but BG-filled defects showed higher metabolic activity than allograft-filled defects at 1-year. The survey of the postoperative period ≥10 years revealed no BG-related adverse events. INTERPRETATION BG granules had similar overall rates of treatment success compared with autografts and allografts, but large-scale trials are needed for the confirmation of clinical equivalence. The extended metabolic activity confirms the expected cellular responses of osseointegrated BG granules.
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Nudging Finnish Adults into Replacing Red Meat with Plant-Based Protein via Presenting Foods as Dish of the Day and Altering the Dish Sequence.
Nykänen, EP, Hoppu, U, Löyttyniemi, E, Sandell, M
Nutrients. 2022;(19)
Abstract
This study investigated whether Finnish working-aged omnivores (n = 163) could be nudged into replacing red meat with a fava-bean-based protein source via "Dish of the Day" (DoD) and main dish sequence alteration (SA) strategies in a controlled real-world Finnish self-service buffet restaurant with smart scales (Flavoria® Multidisciplinary Research Platform). A further aim was to study whether the effectiveness of the strategies differed by gender, age, and body mass index. The participants were assigned one of four experimental treatments: standard menu (T1), DoD (T2), standard menu + SA (T3), or DoD + SA (T4). The participants could choose any amount or combination of salad components and casseroles with minced meat or fava bean protein. Being subjected to a DoD menu and/or SA had no effect on main dish choice or the share of the meat-based dish in the meal weight. Men were more likely to choose a meat-based main dish and had a higher share of the meat dish in the meal weight compared to women, but no differences were observed between those aged 18-29, 30-44, or 45-65 years or those who were normal weight, overweight, or obese. Future studies should have a larger sample size and investigate food choice motives such as price or environmental awareness.
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Discovery of a Novel CIP2A Variant (NOCIVA) with Clinical Relevance in Predicting TKI Resistance in Myeloid Leukemias.
Mäkelä, E, Pavic, K, Varila, T, Salmenniemi, U, Löyttyniemi, E, Nagelli, SG, Ammunét, T, Kähäri, VM, Clark, RE, Elo, LL, et al
Clinical cancer research : an official journal of the American Association for Cancer Research. 2021;(10):2848-2860
Abstract
PURPOSE Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein that inhibits the tumor suppressor PP2A-B56α. However, CIP2A mRNA variants remain uncharacterized. Here, we report the discovery of a CIP2A splicing variant, novel CIP2A variant (NOCIVA). EXPERIMENTAL DESIGN Characterization of CIP2A variants was performed by both 3' and 5' rapid amplification of cDNA ends from cancer cells. The function of NOCIVA was assessed by structural and molecular biology approaches. Its clinical relevance was studied in an acute myeloid leukemia (AML) patient cohort and two independent chronic myeloid leukemia (CML) cohorts. RESULTS NOCIVA contains CIP2A exons 1 to 13 fused to 349 nucleotides from CIP2A intron 13. Intriguingly, the first 39 nucleotides of the NOCIVA-specific sequence are in the coding frame with exon 13 of CIP2A and code for a 13-amino acid peptide tail nonhomologous to any known human protein sequence. Therefore, NOCIVA translates to a unique human protein. NOCIVA retains the capacity to bind to B56α, but, whereas CIP2A is predominantly a cytoplasmic protein, NOCIVA translocates to the nucleus. Indicative of prevalent alternative splicing from CIP2A to NOCIVA in myeloid malignancies, AML and CML patient samples overexpress NOCIVA, but not CIP2A mRNA. In AML, a high NOCIVA/CIP2A mRNA expression ratio is a marker for adverse overall survival. In CML, high NOCIVA expression is associated with inferior event-free survival among imatinib-treated patients, but not among patients treated with dasatinib or nilotinib. CONCLUSIONS We discovered a novel variant of the oncoprotein CIP2A and its clinical relevance in predicting tyrosine kinase inhibitor therapy resistance in myeloid leukemias.
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Bone Marrow Metabolism Is Impaired in Insulin Resistance and Improves After Exercise Training.
Ojala, R, Motiani, KK, Ivaska, KK, Arponen, M, Eskelinen, JJ, Virtanen, KA, Löyttyniemi, E, Heiskanen, MA, U-Din, M, Nuutila, P, et al
The Journal of clinical endocrinology and metabolism. 2020;(12):e4290-303
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CONTEXT Exercise training improves bone mineral density, but little is known about the effects of training on bone marrow (BM) metabolism. BM insulin sensitivity has been suggested to play an important role in bone health and whole-body insulin sensitivity. OBJECTIVE To study the effects of exercise training on BM metabolism. DESIGN Randomized controlled trial. SETTING Clinical research center. PARTICIPANTS Sedentary healthy (n = 28, 40-55 years, all males) and insulin resistant (IR) subjects (n = 26, 43-55 years, males/females 16/10). INTERVENTION Two weeks of sprint interval training or moderate-intensity continuous training. MAIN OUTCOME MEASURES We measured femoral, lumbar, and thoracic BM insulin-stimulated glucose uptake (GU) and fasting free fatty acid uptake (FFAU) using positron-emission tomography and bone turnover markers from plasma. RESULTS At baseline, GU was highest in lumbar, followed by thoracic, and lowest in femoral BM (all Ps < 0.0001). FFAU was higher in lumbar and thoracic than femoral BM (both Ps < 0.0001). BM FFAU and femoral BM GU were higher in healthy compared to IR men and in females compared to males (all Ps < 0.05). Training increased femoral BM GU similarly in all groups and decreased lumbar BM FFAU in males (all Ps < 0.05). Osteocalcin and PINP were lower in IR than healthy men and correlated positively with femoral BM GU and glycemic status (all Ps < 0.05). CONCLUSIONS BM metabolism differs regarding anatomical location. Short-term training improves BM GU and FFAU in healthy and IR subjects. Bone turnover rate is decreased in insulin resistance and associates positively with BM metabolism and glycemic control. CLINICAL TRIAL REGISTRATION NUMBER NCT01344928.