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.

The impact of fish oil and/or probiotics on serum fatty acids and the interaction with low-grade inflammation in pregnant women with overweight and obesity: secondary analysis of a randomised controlled trial.

N-3 long-chain PUFA (LC-PUFA) and probiotics are generally considered to induce health benefits. The objective was to investigate (1) the impact of fish oil and/or probiotics on serum fatty acids (sFA), (2) the interaction of sFA with low-grade inflammation and (3) the relation of sFA to the onset of gestational diabetes mellitus (GDM). Pregnant women with overweight/obesity were allocated into intervention groups with fish oil + placebo, probiotics + placebo, fish oil + probiotics or placebo + placebo in early pregnancy (fish oil: 1·9 g DHA and 0·22 g EPA, probiotics: Lacticaseibacillus rhamnosus HN001 and Bifidobacterium animalis ssp. lactis 420, 1010 CFU, each daily). Blood samples were collected in early (n 431) and late pregnancy (n 361) for analysis of fatty acids in serum phosphatidylcholine (PC), cholesteryl esters (CE), TAG and NEFA with GC and high-sensitivity C-reactive protein and GlycA by immunoassay and NMR spectroscopy, respectively. GDM was diagnosed according to 2 h 75 g oral glucose tolerance test. EPA in PC, CE and TAG and DHA in PC, CE, TAG and NEFA were higher in fish oil and fish oil + probiotics groups compared with placebo. EPA in serum NEFA was lower in women receiving probiotics compared with women not receiving. Low-grade inflammation was inversely associated with n-3 LC-PUFA, which were related to an increased risk of GDM. Fish oil and fish oil + probiotics consumption increase serum n-3 LC-PUFA in pregnant women with overweight/obesity. Although these fatty acids were inversely related to inflammatory markers, n-3 LC-PUFA were linked with an increased risk for GDM.

The effects of a 6-month intervention aimed to reduce sedentary time on skeletal muscle insulin sensitivity: a randomized controlled trial.

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.

Aberrations in the early pregnancy serum metabolic profile in women with prediabetes at two years postpartum.

INTRODUCTION: Aberrations in circulating metabolites have been associated with diabetes and cardiovascular risk. OBJECTIVES: To investigate if early and late pregnancy serum metabolomic profiles differ in women who develop prediabetes by two years postpartum compared to those who remain normoglycemic. METHODS: An NMR metabolomics platform was used to measure 228 serum metabolite variables from women with pre-pregnancy overweight in early and late pregnancy. Co-abundant groups of metabolites were compared between the women who were (n = 40) or were not (n = 138) prediabetic at two years postpartum. Random Forests classifiers, based on the metabolic profiles, were used to predict the prediabetes status, and correlations of the metabolites to glycemic traits (fasting glucose and insulin, HOMA2-IR and HbA1c) and hsCRP at postpartum were evaluated. RESULTS: Women with prediabetes had higher concentrations of small HDL particles, total lipids in small HDL, phospholipids in small HDL and free cholesterol in small HDL in early pregnancy (p = 0.029; adj with pre-pregnancy BMI p = 0.094). The small HDL related metabolites also correlated positively with markers of insulin resistance at postpartum. Similar associations were not detected for metabolites in late pregnancy. A Random Forests classifier based on serum metabolites and clinical variables in early pregnancy displayed an acceptable predictive power for the prediabetes status at postpartum (AUROC 0.668). CONCLUSION: Elevated serum concentrations of small HDL particles in early pregnancy associate with prediabetes and insulin resistance at two years postpartum. The serum metabolic profile during pregnancy might be used to identify women at increased risk for type 2 diabetes.

Fish Oil And/Or Probiotics Intervention in Overweight/Obese Pregnant Women and Overweight Risk in 24-Month-Old Children.

OBJECTIVES: To evaluate whether a fish oil and/or probiotics intervention in pregnant women with overweight or obesity would influence the tendency of their 24-month-old children to become overweight and alter their body fat percentage. METHODS: Women (n = 439) were double-blindly randomized into 4 intervention groups: fish oil+placebo, probiotics+placebo, probiotics+fish oil, and placebo+placebo (fish oil: 1.9 g docosahexaenoic acid and 0.22 g eicosapentaenoic acid, probiotics: Lacticaseibacillus rhamnosus HN001 and Bifidobacterium animalis ssp. lactis 420, 1010 colony-forming units each). The intervention lasted from early pregnancy until 6 months postpartum. Children's (n = 330) growth data (height, weight, head circumference), a secondary outcome of the trial, were evaluated at birth, 3, 6, 12, and 24 months of age and compared to Finnish growth charts. Body fat percentage was measured with air displacement plethysmography (24 months). Logistic regression and general linear models were used to analyze the data. RESULTS: Probiotics+placebo [weight-for-height% adj. Odds ratio (OR) = 0.36, 95% confidence interval (CI) = 0.14-0.95] and probiotics+fish oil [weight-for-age standard deviation score (SD-score) adj. OR = 0.22, 95% CI = 0.07-0.71] associated with lower overweight odds in 24-month-old children compared to placebo+placebo. Results remained essentially the same, when probiotics' main effect (combined probiotics+placebo and probiotics+fish oil) was estimated; that is, lower overweight odds (weight-for-height% adj. OR = 0.48, 95% CI = 0.25-0.95 and weight-for-age SD-score adj. OR = 0.42, 95% CI = 0.20-0.88) compared to non-probiotics. No fish oil main effect (combined fish oil+placebo and probiotics+fish oil) was seen. The intervention did not influence body fat percentage. CONCLUSIONS: The administration of probiotics solely and in combination with fish oil during pregnancy to women with overweight or obesity lowered the overweight odds of their 24-month-old children.

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.

Obesity risk is associated with altered cerebral glucose metabolism and decreased µ-opioid and CB1 receptor availability.

BACKGROUND: Obesity is a pressing public health concern worldwide. Novel pharmacological means are urgently needed to combat the increase of obesity and accompanying type 2 diabetes (T2D). Although fully established obesity is associated with neuromolecular alterations and insulin resistance in the brain, potential obesity-promoting mechanisms in the central nervous system have remained elusive. In this triple-tracer positron emission tomography study, we investigated whether brain insulin signaling, µ-opioid receptors (MORs) and cannabinoid CB1 receptors (CB1Rs) are associated with risk for developing obesity. METHODS: Subjects were 41 young non-obese males with variable obesity risk profiles. Obesity risk was assessed by subjects' physical exercise habits, body mass index and familial risk factors, including parental obesity and T2D. Brain glucose uptake was quantified with [18F]FDG during hyperinsulinemic euglycemic clamp, MORs were quantified with [11C]carfentanil and CB1Rs with [18F]FMPEP-d2. RESULTS: Subjects with higher obesity risk had globally increased insulin-stimulated brain glucose uptake (19 high-risk subjects versus 19 low-risk subjects), and familial obesity risk factors were associated with increased brain glucose uptake (38 subjects) but decreased availability of MORs (41 subjects) and CB1Rs (36 subjects). CONCLUSIONS: These results suggest that the hereditary mechanisms promoting obesity may be partly mediated via insulin, opioid and endocannabinoid messaging systems in the brain.

Iodine status in pregnant women and infants in Finland.

PURPOSE: Iodine insufficiency during pregnancy may adversely influence fetal growth and development. There is a lack of information on iodine status in pregnant women and infants in many countries including Finland. The aim of this study is to determine dietary intake of iodine and the iodine status in a population of Finnish pregnant women and their infants. METHODS: Urine samples were collected from women participating in a mother-child clinical study at early (n = 174) and late pregnancy (n = 186) and at three months of postpartum (n = 197), when infant samples were also collected (n = 123). Urine iodine concentration was measured using inductively coupled plasma mass spectrometry. Cutoffs for iodine insufficiency were < 150 µg/L during pregnancy and < 100 µg/L at postpartum and in infants. Iodine intake was assessed using 3-day food diaries. RESULTS: Increased risk of insufficiency, based on urinary iodine concentrations, was observed in the groups investigated in this study. Of the women studied, 66% had urinary iodine concentrations indicating insufficient intakes and iodine insufficiency at early pregnancy, 70% at late pregnancy and 59% at three months of postpartum. This was also the case in 29% of the three-month-old infants. Estimation of iodine intake revealed that iodine insufficient women had lower intakes of iodine from the diet, from food supplements and from diet plus supplements than iodine sufficient women in early pregnancy and at three months of post-partum. In late pregnancy, this difference was seen for iodine intake from supplements. CONCLUSION: The majority of the women manifested with low urine iodine concentrations both during and after pregnancy. Similarly, one-third of the infants presented with iodine insufficiency. Maternal iodine intake data support these findings. These observations may have implications for optimal child cognitive development.

A healthy dietary pattern with a low inflammatory potential reduces the risk of gestational diabetes mellitus.

PURPOSE: An optimal diet for lowering the risk of gestational diabetes mellitus (GDM) is still to be defined, but may comprise of nutrient intakes, dietary patterns, diet quality, and eating frequency. This study was designed to investigate the contribution of diet in developing GDM in a comprehensive way. METHODS: The dietary intake of overweight or obese women, a risk group for GDM (n = 351), was assessed using 3-day food diaries and diet quality questionnaires in early pregnancy. Eating frequency and nutrient intakes were calculated, and dietary patterns identified using principal component analysis. The inflammatory potential of the diet was determined by calculating the dietary inflammatory index (DII®) and energy-adjusted DII (E-DII™). GDM was diagnosed with an oral glucose tolerance test at 24-28 gestational weeks. RESULTS: Higher adherence to 'healthier dietary pattern' characterized by consumptions of vegetables and rye bread associated with a reduced risk of GDM (adjusted OR 0.27, 95% CI 0.11-0.70). Higher E-DII score, indicating pro-inflammatory diet, was associated with a 27% higher risk of GDM (adjusted OR 1.27; 95% CI 1.08-1.49) for each E-DII point. In the evaluation of nutrient intakes, total fat, saturated fatty acids (SFAs), and trans fatty acids were higher and fiber lower in women developing GDM compared to women not developing GDM (all p < 0.05). Intakes of total fat, SFAs, and trans fatty acids were also significant predictors for GDM (all p < 0.05). CONCLUSIONS: The results emphasize the importance of an overall healthy diet and limitation of foods with SFAs, and other nutrients with a high inflammatory potential in reducing the risk of GDM. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01922791, August 14, 2013.

Metagenomics analysis of gut microbiota in response to diet intervention and gestational diabetes in overweight and obese women: a randomised, double-blind, placebo-controlled clinical trial.

OBJECTIVE: Gut microbiota and diet are known to contribute to human metabolism. We investigated whether the metagenomic gut microbiota composition and function changes over pregnancy are related to gestational diabetes mellitus (GDM) and can be modified by dietary supplements, fish oil and/or probiotics. DESIGN: The gut microbiota of 270 overweight/obese women participating in a mother-infant clinical study were analysed with metagenomics approach in early (mean gestational weeks 13.9) and late (gestational weeks 35.2) pregnancy. GDM was diagnosed with a 2 hour 75 g oral glucose tolerance test. RESULTS: Unlike women with GDM, women without GDM manifested changes in relative abundance of bacterial species over the pregnancy, particularly those receiving the fish oil + probiotics combination. The specific bacterial species or function did not predict the onset of GDM nor did it differ according to GDM status, except for the higher abundance of Ruminococcus obeum in late pregnancy in the combination group in women with GDM compared with women without GDM. In the combination group, weak decreases over the pregnancy were observed in basic bacterial housekeeping functions. CONCLUSIONS: The specific gut microbiota species do not contribute to GDM in overweight/obese women. Nevertheless, the GDM status may disturb maternal gut microbiota flexibility and thus limit the capacity of women with GDM to respond to diet, as evidenced by alterations in gut microbiota observed only in women without GDM. These findings may be important when considering the metabolic complications during pregnancy, but further studies with larger populations are called for to verify the findings.

Weight gain and body composition during pregnancy: a randomised pilot trial with probiotics and/or fish oil.

We evaluated the effects of fish oil and/or probiotic supplementation in a randomised placebo-controlled intervention pilot trial on gestational weight gain (GWG) and body composition. Additionally, the influence of gestational diabetes (GDM) on GWG and body composition was assessed. We randomised 439 overweight women into intervention groups: fish oil + placebo, probiotics + placebo, fish oil + probiotics and placebo + placebo (fish oil: 1·9 g DHA and 0·22 g EPA and probiotics: Lactobacillus rhamnosus HN001 and Bifidobacterium animalis ssp. lactis 420, 1010 colony-forming units each). GDM was diagnosed with oral glucose tolerance test. Body composition was measured with air displacement plethysmography at randomisation (mean 13·9) and in late pregnancy (mean 35·2 gestational weeks). Intervention did not influence mean GWG or change in body fat mass/percentage (P > 0·17). Body composition in early pregnancy did not differ between the women who did or did not develop GDM (adjusted P > 0·23). Compared with the normoglycaemic women (n 278), women diagnosed with GDM (n 119) gained less weight (7·7 (sd 0·4) v. 9·3 (sd 0·4) kg, adjusted mean difference -1·66 (95 % CI -2·52, -0·80) and fat mass (0·4 (sd 0·4) v. 1·8 (sd 0·3) kg, adjusted mean difference -1·43 (95 % CI -2·19, -0·67) during the follow-up. In conclusion, adiposity of pregnant overweight women was not affected by supplementation with fish oil and/or probiotics, nor did it predict the development of GDM. However, adiposity was reduced in women with GDM compared with normoglycaemic women irrespective of the dietary intervention.

GlycA, a novel marker for low grade inflammation, reflects gut microbiome diversity and is more accurate than high sensitive CRP in reflecting metabolomic profile.

INTRODUCTION: Gut microbiota is, along with adipose tissue, recognized as a source for many metabolic and inflammatory disturbances that may contribute to the individual's state of health. OBJECTIVES: We investigated in cross-sectional setting the feasibility of utilizing GlycA, a novel low grade inflammatory marker, and traditional low grade inflammatory marker, high sensitivity CRP (hsCRP), in reflecting serum metabolomics status and gut microbiome diversity. METHODS: Fasting serum samples of overweight/obese pregnant women (n = 335, gestational weeks: mean 13.8) were analysed for hsCRP by immunoassay, GlycA and metabolomics status by NMR metabolomics and faecal samples for gut microbiome diversity by metagenomics. The benefits of GlycA as a metabolic marker were investigated against hsCRP. RESULTS: The GlycA concentration correlated with more of the metabolomics markers (144 out of 157), than hsCRP (55 out of 157) (FDR < 0.05). The results remained essentially the same when potential confounding factors known to associate with GlycA and hsCRP levels were taken into account (P < 0.05). This was attributable to the detected correlations between GlycA and the constituents and concentrations of several sized VLDL-particles and branched chain amino acids, which were statistically non-significant with regard to hsCRP. GlycA, but not hsCRP, correlated inversely with gut microbiome diversity. CONCLUSION: GlycA is a superior marker than hsCRP in assessing the metabolomic profile and gut microbiome diversity. It is proposed that GlycA may act as a novel marker that reflects both the gut microbiome and adipose tissue originated metabolic aberrations; this proposal will need to be verified with regard to clinical outcomes. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT01922791, August 14, 2013.

Distinct Metabolic Profile in Early Pregnancy of Overweight and Obese Women Developing Gestational Diabetes.

BACKGROUND: Reliable biomarkers for gestational diabetes mellitus (GDM) would be beneficial in the early prevention of adverse metabolic outcomes during pregnancy and beyond. OBJECTIVES: The objective of this study was to investigate whether the early pregnancy serum metabolic profile differs in women developing GDM from those remaining healthy. Furthermore, we evaluated the potential of these metabolites to act as predictive markers for GDM. METHODS: This was a prospective study investigating overweight and obese [prepregnancy BMI (in kg/m2) ≥25 and >30, respectively] pregnant women (prepregnancy median BMI: 28.5; IQR: 26.4-31.5; n = 357). Fasting serum samples were analyzed with a targeted NMR approach in early pregnancy (median: 14.3 weeks of gestation). GDM was diagnosed on the basis of a 2-h, 75-g oral-glucose-tolerance test at a median of 25.7 weeks of gestation. RESULTS: In early pregnancy, 78 lipid metabolites differed in women who later developed GDM (n = 82) compared with those who remained healthy (n = 275) (ANCOVA, adjusted for confounding factors and corrected for multiple comparisons; false discovery rate <0.05). Higher concentrations of several-sized VLDL particles and medium- and small-sized HDL particles, and lower concentrations of very large-sized HDL particles, were detected in women developing GDM. Furthermore, concentrations of amino acids including 2 branched-chain amino acids, isoleucine and leucine, and GlycA, a marker for low-grade inflammation, were higher in women who developed GDM. Receiver operating characteristic analysis revealed that the most predictive marker for GDM was a higher concentration of small-sized HDL particles (AUC: 0.71; 95% CI: 0.67, 0.77; P < 0.001). CONCLUSIONS: We identified a distinct early pregnancy metabolomic profile especially attributable to small HDL particles in women developing GDM. The aberrant metabolic profile could represent a novel way to allow early identification of this most common medical condition affecting pregnant women. This trial was registered at clinicaltrials.gov as NCT01922791.

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.

Gut microbiota composition and function in pregnancy as determinants of prediabetes at two-year postpartum.

AIMS: Deep metagenomics offers an advanced tool for examining the relationship between gut microbiota composition and function and the onset of disease; in this case, does the composition and function of gut microbiota during pregnancy differ in women who develop prediabetes and those who do not at two-year postpartum, and whether the gut microbiota composition associates with glycemic traits. METHODS: In total, 439 women were recruited in early pregnancy. Gut microbiota was assessed by metagenomics analysis in early (13.9 ± 2.0 gestational weeks) and late pregnancy (35.1 ± 1.0 gestational weeks). Prediabetes was determined using American Diabetes Association criteria as fasting plasma glucose 5.6-6.9 mmol/l analyzed by an enzymatic hexokinase method. Of the women, 39 (22.1%) developed prediabetes by two-year postpartum. RESULTS: The relative abundances of Escherichia unclassified (FDR < 0.05), Clostridiales bacterium 1_7_ 47FAA (FDR < 0.25) and Parabacteroides (FDR < 0.25) were higher, and those of Ruminococcaceae bacterium D16 (FDR < 0.25), Anaerotruncus unclassified (FDR < 0.25) and Ruminococcaceae noname (FDR < 0.25) were lower in early pregnancy in those women who later developed prediabetes. In late pregnancy, Porphyromonas was higher and Ruminococcus sp 5_1_39BFAA was lower in prediabetes (FDR < 0.25). Furthermore, fasting glucose concentrations associated inversely with Anaerotruncus unclassified in early pregnancy and directly with Ruminococcus sp 5_1_39BFAA in late pregnancy (FDR < 0.25). α-Diversity or ß-diversity did not differ significantly between the groups. Predictions of community function during pregnancy were not associated with prediabetes. CONCLUSIONS: Our study shows that some bacterial species during pregnancy contributed to the onset of prediabetes within two-year postpartum. These were attributable primarily to a lower abundance of short-chain fatty acids-producing bacteria.

Reducing Sedentary Time and Whole-Body Insulin Sensitivity in Metabolic Syndrome: A 6-Month Randomized Controlled Trial.

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.

Distinct Diet-Microbiota-Metabolism Interactions in Overweight and Obese Pregnant Women: a Metagenomics Approach.

Diet and gut microbiota are known to modulate metabolic health. Our aim was to apply a metagenomics approach to investigate whether the diet-gut microbiota-metabolism and inflammation relationships differ in pregnant overweight and obese women. This cross-sectional study was conducted in overweight (n = 234) and obese (n = 152) women during early pregnancy. Dietary quality was measured by a validated index of diet quality (IDQ). Gut microbiota taxonomic composition and species diversity were assessed by metagenomic profiling (Illumina HiSeq platform). Markers for glucose metabolism (glucose, insulin) and low-grade inflammation (high sensitivity C-reactive protein [hsCRP], glycoprotein acetylation [GlycA]) were analyzed from blood samples. Higher IDQ scores were positively associated with a higher gut microbiota species diversity (r = 0.273, P = 0.007) in obese women, but not in overweight women. Community composition (beta diversity) was associated with the GlycA level in the overweight women (P = 0.04) but not in the obese. Further analysis at the species level revealed a positive association between the abundance of species Alistipes finegoldii and the GlycA level in overweight women (logfold change = 4.74, P = 0.04). This study has been registered at ClinicalTrials.gov under registration no. NCT01922791 (https://clinicaltrials.gov/ct2/show/NCT01922791). IMPORTANCE We observed partially distinct diet-gut microbiota-metabolism and inflammation responses in overweight and obese pregnant women. In overweight women, gut microbiota community composition and the relative abundance of A. finegoldii were associated with an inflammatory status. In obese women, a higher dietary quality was related to a higher gut microbiota diversity and a healthy inflammatory status.

Effects of reduced sedentary time on cardiometabolic health in adults with metabolic syndrome: A three-month randomized controlled trial.

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.

Potential pathobionts in vaginal microbiota are affected by fish oil and/or probiotics intervention in overweight and obese pregnant women.

New means to stabilize the microbial balance during pregnancy could benefit maternal health. Our objectives were to investigate in overweight/obese pregnant women 1) the impact of long-chain polyunsaturated fatty acids (fish oil) and/or probiotics on the vaginal microbiota, 2) its relation to gestational diabetes mellitus (GDM) and 3) its interaction with vaginal active matrix metalloproteinase-8 (aMMP-8) and serum high sensitivity C-reactive protein (hsCRP) and phosphorylated insulin-like growth factor-binding protein-1 (phIGFBP-1), IGFBP-1 and aMMP-8. The women were allocated to fish oil + placebo, probiotics + placebo, fish oil + probiotics and placebo + placebo-groups, from early pregnancy onwards (fish oil: 1.9 g docosahexaenoic acid and 0.22 g eicosapentaenoic acid; probiotics: Lacticaseibacillus rhamnosus HN001 (formerly Lactobacillus rhamnosus HN001) and Bifidobacterium animalis ssp. lactis 420, 1010 colony-forming units each). Vaginal and serum samples (early pregnancy, n = 112; late pregnancy, n = 116), were analyzed for vaginal microbiota using 16S rRNA gene amplicon sequencing and vaginal aMMP-8 and serum hsCRP, aMMP-8, phIGFBP-1 and IGFBP-1 by immunoassays. GDM was diagnosed from a 2-h 75 g OGTT. ClinicalTrials.gov, NCT01922791. The intervention exerted effects on many low-abundant bacteria. Compared to the placebo-group, there was a lower abundance of potential pathobionts, namely Ureaplasma urealyticum in the fish oil-group, Ureaplasma, U. urealyticum and Prevotella disiens in the probiotics-group, Dialister invisus and Prevotella timonensis in the fish oil + probiotics-group. Moreover, probiotics decreased the abundance of a few potential pathobionts during pregnancy. Many bacteria were related to GDM. The vaginal aMMP-8 level correlated significantly with α-diversity and inversely with two Lactobacillus species. Dietary interventions, especially probiotics, may have beneficial effects on the vaginal microbiota during pregnancy.