Sedentary time associates detrimentally and physical activity beneficially with metabolic flexibility in adults with metabolic syndrome.

Metabolic flexibility (MetFlex) describes the ability to respond and adapt to changes in metabolic demand and substrate availability. The relationship between physical (in)activity and MetFlex is unclear. This study aimed to determine whether sedentary time, physical activity (PA), and cardiorespiratory fitness associate with MetFlex. Sedentary time, standing, and PA were measured with accelerometers for 4 weeks in 64 sedentary adults with metabolic syndrome [37 women, 27 men; 58.3 (SD 6.8) years]. Fitness (V̇o2max; mL·kg-1·min-1) was measured with graded maximal cycle ergometry. MetFlex was assessed with indirect calorimetry as the change in respiratory exchange ratio (ΔRER) from fasting to insulin stimulation with hyperinsulinemic-euglycemic clamp and from low-intensity to maximal exercise. Carbohydrate (CHOox) and fat oxidation (FATox) were calculated from respiratory gases. High sedentary time associated with higher fasting RER [ß = 0.35 (95% confidence interval: 0.04, 0.67)], impaired insulin-stimulated MetFlex (ΔRER) [ß=-0.41 (-0.72, -0.09)], and lower fasting FATox [ß=-0.36 (-0.67, -0.04)]. Standing associated with lower fasting RER [ß=-0.32 (-0.62, -0.02)]. Higher standing time and steps/day associated with higher fasting FATox [ß = 0.31 (0.01, 0.61), and ß = 0.26 (0.00, 0.53)]. Light-intensity and total PA associated with better insulin-stimulated MetFlex [ß = 0.33 (0.05, 0.61)], and ß = 0.33 (0.05, 0.60)]. Higher V̇o2max associated with higher CHOox during maximal exercise [ß = 0.81 (0.62, 1.00)], as well as during insulin stimulation [ß = 0.43 (0.13, 0.73)]. P values are less than 0.05 for all associations. Sedentary time and PA associate with MetFlex. Reducing sitting and increasing PA of even light intensity might aid in the prevention of metabolic diseases in risk populations through their potential effects on energy metabolism.NEW & NOTEWORTHY High accelerometer-assessed sedentary time associates with metabolic inflexibility measured during hyperinsulinemic-euglycemic clamp in adults with metabolic syndrome, and more light-intensity and total physical activity associate with more metabolic flexibility. Physical activity behaviors may thus play an important role in the regulation of fuel metabolism. This highlights the potential of reduced sedentary time and increased physical activity of any intensity to induce metabolic health benefits and help in disease prevention in risk populations.

Effects of reducing sedentary behavior on cardiorespiratory fitness in adults with metabolic syndrome: A 6-month RCT.

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 .

Associations of sedentary time, physical activity, and fitness with muscle glucose uptake in adults with metabolic syndrome.

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 VO2 max with cycle ergometry in 44 sedentary adults with metabolic syndrome. Thigh muscle GU was determined with [18 F]FDG-PET imaging. RESULTS: Sedentary time (ß = -0.374), standing (ß = 0.376), steps (ß = 0.351), and VO2 max (ß = 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.

Maximal Exercise Capacity in Chronic Kidney Disease Stage 4-5 Patients Transitioning to Renal Replacement Therapy or Continuing Conservative Care: A Longitudinal Follow-Up Study.

INTRODUCTION: Chronic kidney disease (CKD) is associated with impaired maximal exercise capacity (MEC). However, data are scarce on the development of MEC in CKD stage 4-5 patients transitioning to renal replacement therapy (RRT). METHODS: We explored the change in MEC measured in watts (Wlast4) with 2 consecutive maximal bicycle stress ergometry tests in 122 CKD stage 4-5 patients transitioning to dialysis and transplantation in an observational follow-up study. RESULTS: Mean age was 58.9 ± 13.9 years and 43 (35.2%) were female. Mean time between the baseline and follow-up ergometry tests was 1,012 ± 327 days and 29 (23.8%) patients had not initiated RRT, 50 (41.0%) were undergoing dialysis, and 43 (35.2%) had received a kidney transplant at the time of the follow-up ergometry test. The mean Wlast4 was 91 ± 37 W and 84 ± 37 W for the baseline and follow-up ergometry tests, respectively (p < 0.001). The mean Wlast4 declined between the baseline and follow-up ergometry tests in patients not requiring RRT (p = 0.001) and transplant recipients (p = 0.005), but not in dialysis patients (p = 0.478). There were no differences in the ratio of Wlast4 of the follow-up to the baseline ergometry tests (∆Wlast4) between patients on different treatment modalities at the time of the follow-up test (p = 0.097). Mean capillary blood bicarbonate was significantly associated with ∆Wlast4 after adjusting for age and treatment modality in the multivariate linear regression analysis (ß = 0.226, p = 0.012). CONCLUSION: MEC declined or remained poor in advanced CKD patients transitioning to RRT or continuing conservative care in this observational study. Mean capillary blood bicarbonate was independently associated with the development of MEC.

Physical inactivity from youth to adulthood and adult cardiometabolic risk profile.

Adults with a low physical activity (PA) level are at increased risk for cardiometabolic diseases, but little is known on the association between physical inactivity since youth and cardiometabolic health in adulthood. We investigated the association of persistent physical inactivity from youth to adulthood with adult cardiometabolic risk factors. Data were drawn from the ongoing Cardiovascular Risk in Young Finns Study with seven follow-ups between 1980 and 2011 (baseline age 3-18 years, n = 1961). Physical activity data from a standardized questionnaire was expressed as a PA-index. Using the PA-index, four groups were formed: 1)persistently physically inactive (n = 246), 2)decreasingly active (n = 305), 3)increasingly active (n = 328), and 4)persistently active individuals (n = 1082). Adulthood cardiometabolic risk indicators included waist circumference, body mass index (BMI), blood pressure, and fasting lipids, insulin, and glucose. Clustered cardiometabolic risk was defined using established criteria for metabolic syndrome. Persistently physically inactive group was used as a reference. Compared to the persistently physically inactive group, those who were persistently active had lower risk for adult clustered cardiometabolic risk (RR = 0.67;CI95% = 0.53-0.84; Harmonized criteria), obesity (BMI > 30 kg/m2, RR = 0.76;CI95% = 0.59-0.98), high waist circumference (RR = 0.82;CI95% = 0.69-0.98), and high triglyceride (RR = 0.60;CI95% = 0.47-0.75), insulin (RR = 0.58;CI95% = 0.46-0.74) and glucose (RR = 0.77;CI95% = 0.62-0.96) concentrations as well as low high-density lipoprotein cholesterol (HDLC) concentration (RR = 0.78;CI95% = 0.66-0.93). Comparable results were found when persistently physically inactive individuals were compared with those who increased PA. The results remained essentially similar after adjustment for education, diet, smoking, and BMI. Persistently physically inactive lifestyle since youth is associated with an unfavorable cardiometabolic risk profile in adulthood. Importantly, even minor increase in PA lowers the cardiometabolic risk.

Interatrial block, P terminal force or fragmented QRS do not predict new-onset atrial fibrillation in patients with severe chronic kidney disease.

BACKGROUND: The prevalence of left atrial enlargement (LAE) and fragmented QRS (fQRS) diagnosed using ECG criteria in patients with severe chronic kidney disease (CKD) is unknown. Furthermore, there is limited data on predicting new-onset atrial fibrillation (AF) with LAE or fQRS in this patient group. METHODS: We enrolled 165 consecutive non-dialysis patients with CKD stage 4-5 without prior AF diagnosis between 2013 and 2017 in a prospective follow-up cohort study. LAE was defined as total P-wave duration ≥120 ms in lead II ± > 1 biphasic P-waves in leads II, III or aVF; or duration of terminal negative portion of P-wave > 40 ms or depth of terminal negative portion of P-wave > 1 mm in lead V1 from a baseline ECG, respectively. fQRS was defined as the presence of a notched R or S wave or the presence of ≥1 additional R waves (R') or; in the presence of a wide QRS complex (> 120 ms), > 2 notches in R or S waves in two contiguous leads corresponding to a myocardial region, respectively. RESULTS: Mean age of the patients was 59 (SD 14) years, 56/165 (33.9%) were female and the mean estimated glomerular filtration rate was 12.8 ml/min/1.73m2. Altogether 29/165 (17.6%) patients were observed with new-onset AF within median follow-up of 3 [IQR 3, range 2-6] years. At baseline, 137/165 (83.0%) and 144/165 (87.3%) patients were observed with LAE and fQRS, respectively. Furthermore, LAE and fQRS co-existed in 121/165 (73.3%) patients. Neither findings were associated with the risk of new-onset AF within follow-up. CONCLUSION: The prevalence of LAE and fQRS at baseline in this study on CKD stage 4-5 patients not on dialysis was very high. However, LAE or fQRS failed to predict occurrence of new-onset AF in these patients.

Effects of reduced sedentary time on resting, exercise and post-exercise blood pressure in inactive adults with metabolic syndrome - a six-month exploratory RCT.

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.

Daily standing time, dietary fiber, and intake of unsaturated fatty acids are beneficially associated with hepatic insulin sensitivity in adults with metabolic syndrome.

Background: Obesity is associated with impaired glucose metabolism and hepatic insulin resistance. The aim was to investigate the associations of hepatic glucose uptake (HGU) and endogenous glucose production (EGP) to sedentary behavior (SB), physical activity (PA), cardiorespiratory fitness, dietary factors, and metabolic risk markers. Methods: Forty-four adults with metabolic syndrome (mean age 58 [SD 7] years, BMI ranging from 25-40kg/; 25 females) were included. HGU was measured by positron emission tomography during the hyperinsulinemic-euglycemic clamp. EGP was calculated by subtracting the glucose infusion rate during clamp from the glucose rate of disappearance. SB and PA were measured with hip-worn accelerometers (26 [SD3] days). Fitness was assessed by maximal bicycle ergometry with respiratory gas measurements and dietary intake of nutrients by 4-day food diaries. Results: HGU was not associated with fitness or any of the SB or PA measures. When adjusted for sex, age, and body fat-%, HGU was associated with whole-body insulin sensitivity (ß=0.58), water-insoluble dietary fiber (ß=0.29), energy percent (E%) of carbohydrates (ß=-0.32), saccharose (ß=-0.32), mono- and polyunsaturated fatty acids (ß=0.35, ß=0.41, respectively). EGP was associated with whole-body insulin sensitivity (ß=-0.53), and low-density lipoprotein cholesterol [ß=-0.31], and when further adjusted for accelerometry wear time, EGP was associated with standing [ß=-0.43]. (p-value for all< 0.05). Conclusions: Standing more, consuming a diet rich in fiber and unsaturated fatty acids, and a lower intake of carbohydrates, especially sugar, associate beneficially with hepatic insulin sensitivity. Habitual SB, PA, or fitness may not be the primary modulators of HGU and EGP. However, these associations need to be confirmed with intervention studies.

Relationship between liver fat content and lifestyle factors in adults with metabolic syndrome.

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.

Association between cardiorespiratory fitness and metabolic health in overweight and obese adults.

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 (V̇O2peak) 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: V̇O2peak and Wpeak were assessed by a maximal cycle ergometer exercise test. FFM was measured by air displacement plethysmograph 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: V̇O2peak and Wpeak scaled by BM-1 were inversely associated with insulin (ß=-0.404 to -0.372, 95% CI: -0.704 to -0.048), HOMA-IR (ß=-0.442 to -0.440, 95% CI: -0.762 to -0.117), and MetS (ß=-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.

Elevated Troponin T and Enlarged Left Atrium Are Associated with the Incidence of Atrial Fibrillation in Patients with CKD Stage 4-5.

INTRODUCTION: Atrial fibrillation (AF) and CKD are commonly coexisting conditions. However, data on epidemiology of AF in patients with CKD stage 4-5 is scarce. METHODS: We prospectively enrolled 210 consecutive non-dialysis patients with CKD stage 4-5 between 2013 and 2017. Follow-up data on AF incidence along with medical history, laboratory tests, and echocardiography at baseline were gathered. RESULTS: At baseline, mean age was 62 years, estimated glomerular filtration rate 12.8 mL/min, and 73/210 (34.8%) participants were female. Altogether, 41/210 (19.5%) patients had a previous diagnosis of AF. After median follow-up of 46 [IQR 27] months, new-onset AF occurred in 33/169 (19.5%) patients (69.9 events/1,000 person-years). In the Cox proportional hazard model, age >60 years (HR 4.27, CI 95% 1.57-11.64, p < 0.01), elevated troponin T (TnT) >50 ng/L (HR 3.61, CI 95% 1.55-8.37, p < 0.01), and left atrial volume index (LAVI) >30 mL/m2 (HR 4.82, CI 95% 1.11-21.00, p = 0.04) were independently associated with the incidence of new-onset AF. CONCLUSION: The prevalence and incidence of AF was markedly high in this prospective study on patients with CKD stage 4-5. Elevated TnT and increased LAVI were independently associated with the occurrence of new-onset AF in patients with severe CKD.

Standing is associated with insulin sensitivity in adults with metabolic syndrome.

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 (ß = -0.384; ß = 0.400; ß = 0.350; ß = 0.609, respectively), HOMA-IR (ß = 0.420; ß = -0.548; ß = -0.252; ß = -0.449), and insulin (ß = 0.433; ß = -0.541; ß = -0.252; ß = -0.453); all p-values < 0.05. Breaks associated only with M-value (ß = 0.277). When further adjusted for body fat %, only standing remained significantly associated with HOMA-IR (ß = -0.381) and insulin (ß = -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.

Cardiac troponin elevations in marathon runners. Role of coronary atherosclerosis and skeletal muscle injury. The MaraCat Study.

BACKGROUND: Marathon running is associated with transient risk of sudden cardiac death and high cardiac troponin levels are common after race. There is limited data whether coronary atherosclerosis or skeletal muscle injury are related to troponin release caused by strenuous exercise. We aimed to assess whether coronary artery calcification (CAC), plaque vulnerability or skeletal muscle injury relate to cardiac troponin T (cTnT) elevations after marathon race. METHODS: In this observational study, 40 male runners participating in Paavo Nurmi 2018 Marathon were recruited with an open email invitation to evaluate the prevalence of post-race cTnT elevations and their predictors. In addition to baseline and post-race laboratory investigations, 28 runners aged >44 years underwent CAC measurement with computed tomography. Coronary plaque vulnerability was evaluated by free pregnancy-associated plasma protein A (fPAPP-A) concentration and skeletal muscle injury by skeletal troponin I (skTnI) measurement. RESULTS: The post-marathon cTnT concentrations rose above the normal reference limit in 38 (95%) participants. A 10-fold increase in skTnI concentrations was observed and elevated post-race values were seen in all participants. The correlation between the post-race cTnT and post-race skTnI (rs = -0.26, p = 0.11) was non-significant. CAC was detected (Agatston score > 0) in 15 (53.6%) participants, with a median score of 2.0 (interquartile range [IQR] 80). There was no correlation between cTnT with CAC score or post-race fPAPP-A levels. CONCLUSIONS: Asymptomatic cardiac troponin elevations are common after prolonged strenuous exercise, but are not related to markers of coronary atherosclerosis, plaque vulnerability or skeletal muscle injury.

Physical Inactivity from Youth to Adulthood and Risk of Impaired Glucose Metabolism.

INTRODUCTION: Physical activity (PA) is important in the prevention and treatment of impaired glucose metabolism. However, association of physical inactivity during the transition between childhood and adulthood with glucose metabolism is unknown. Therefore, we studied the association of persistent physical inactivity since childhood with glucose metabolism in adulthood. METHODS: Data were drawn from the ongoing, Cardiovascular Risk in Young Finns Study with repeated follow-ups between 1980 and 2011 (baseline age, 3-18 yr; n = 3596). Impaired glucose metabolism was defined as having impaired fasting glucose (6.1-6.9 mmol·L) or type 2 diabetes in adulthood. Leisure-time PA habits were repeatedly collected with a standardized questionnaire and expressed as a PA Index. Using PA Index, four groups were formed (n = 2000): 1) persistently low PA, 2) decreasingly active, 3) increasingly active, and 4) persistently active subjects. Poisson regression model was used to examine the association between PA groups and impaired glucose metabolism. RESULTS: The proportion of the sample with impaired glucose metabolism was 16.1% in individuals with persistently low PA, 14.5% in decreasingly active, 6.8% in increasingly active, and 11.1% in persistently active. Compared with individuals with persistently low PA, age and sex-adjusted risk for impaired glucose metabolism were lower in those who increased PA (relative risk [RR], 0.47; 95% confidence interval [CI], 0.29-0.76) and in those who were persistently active (RR, 0.70; 95% CI, 0.51-0.97), but similar in those who decreased PA (RR, 0.93; 95% CI, 0.66-1.36). CONCLUSIONS: Persistently physically inactive lifestyle from youth to adulthood is associated with increased risk of impaired glucose metabolism in adulthood. Importantly, a moderate increase in PA lowered the risk. The results highlight the importance of avoiding physically inactive lifestyle at all stages of life.