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Diet may influence the gut microbiota and subsequently affect the host's health. Recent developments in methods analyzing the composition and function of the gut microbiota allow a deeper understanding of diet-gut microbiota relationships. A state-of-the-art methodology, shotgun metagenomics sequencing, offers a higher taxonomic resolution of the gut microbiota at the bacterial species and strain levels, and more accurate information regarding the functional potential of gut microbiota. Here, the available evidence on the relationship between diet and gut microbiota was critically reviewed, focusing on results emerging from recent metagenomics sequencing studies applied in randomized controlled trials and observational studies. The PubMed and Embase databases were used to search publications between January 2011 and September 2023. Thus far, the number of studies is limited, and the study designs and methods utilized have been variable. Nevertheless, the cumulative evidence from interventions relates to dietary fiber as a modifier of bacterial species, such as Anaerostipes hadrus and Faecalibacterium prausnitzii. Furthermore, observational studies have detected associations between different dietary patterns and food groups with certain microbial species. Utilization of metagenomics sequencing is becoming more common and will undoubtedly provide further insights into diet-gut microbiota relationships at the species level as well as their functional pathways in the near future. For reproducible results and to draw reliable conclusions across various studies on diet-gut microbiota relationships, there is a need for harmonization of the study designs and standardized ways of reporting., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Life Sciences Institute.)

The aim of this study was to investigate whether a reduction in accelerometer-measured sedentary behavior (SB) improves blood lipids in inactive adults with metabolic syndrome (MetS). Sixty-four participants were randomly assigned into intervention (INT, n = 33) and control (CONT, n = 31) groups. The INT group was instructed to reduce SB by 1 h/day without increasing formal exercise, whereas the CONT group was advised to maintain usual SB habits. SB and physical activity (PA) were measured with accelerometers throughout the intervention. Plasma lipid concentrations and dietary intake by food diaries were assessed at baseline and at the end of the intervention. High-density lipoprotein percentage of total cholesterol decreased during the intervention similarly in both groups (p = 0.047). Other blood lipids did not change from baseline to six months in either group. The CONT group had a statistically significant reduction in the intake of saturated fatty acids compared to the INT group (p = 0.03). Intervention resulting in a 40-minute reduction in daily SB and 20-minute increase in habitual MVPA seems to not be effective in improving blood lipids in adults with MetS. Reducing SB together with a higher volume and/or intensity of PA and proper nutrition may be needed to reduce the risk of cardiometabolic diseases.Trial registration. This study is registered at ClinicalTrials.gov (NCT03101228, 05/04/2017). https://www.clinicaltrials.gov/ct2/show/NCT03101228?term=NCT03101228&draw=2&rank=1 ., (© 2024. The Author(s).)

Objectives: Sedentary behaviour (SB) is a plausible intervention target for back pain mitigation. Therefore, this study aimed to investigate the effects of a 6-month SB reduction intervention on back pain and related disability outcomes, and paraspinal muscle (ie, erector spinae and transversospinales separately) insulin sensitivity (glucose uptake, GU) and muscle fat fraction (FF)., Methods: Sixty-four adults with overweight or obesity and metabolic syndrome were randomised into intervention (n=33) and control (n=31) groups. The intervention group aimed to reduce SB by 1 hour/day (measured with accelerometers) and the control group continued as usual. Back pain intensity and pain-related disability were assessed using 10 cm Visual Analogue Scales and the Oswestry Disability Index (ODI) questionnaire. Paraspinal muscle GU was measured using 18-fluorodeoxyglucose positron emission tomography during hyperinsulinaemic-euglycaemic clamp. FF was measured using MRI., Results: Pain-related disability increased during the intervention in both groups. Back pain intensity increased significantly more in the control group than in the intervention group in which back pain intensity remained unchanged (group×time p=0.030). No statistically significant between-group changes in pain-related disability, ODI or paraspinal GU and FF were observed. In the whole study group, the change in daily steps was associated positively with the change in paraspinal muscle GU., Conclusion: An intervention focusing on SB reduction may be feasible for preventing back pain worsening regardless of paraspinal muscle GU or FF., Trial Registration Number: NCT03101228., Competing Interests: Competing interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: TS received a speaker fee from Pihlajalinna Plc, Tampere, Finland. The other authors report no conflicts of interest. The results are presented clearly and honestly without fabrication, falsification or inappropriate data manipulation., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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 (β=0.58), water-insoluble dietary fiber (β=0.29), energy percent (E%) of carbohydrates (β=-0.32), saccharose (β=-0.32), mono- and polyunsaturated fatty acids (β=0.35, β=0.41, respectively). EGP was associated with whole-body insulin sensitivity (β=-0.53), and low-density lipoprotein cholesterol [β=-0.31], and when further adjusted for accelerometry wear time, EGP was associated with standing [β=-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., Competing Interests: JK received consultancy fees from GE Healthcare and AstraZeneca and speaker fees from GE Healthcare, Bayer, Lundbeck, Boehringer-Ingelheim, and Merck, outside of the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Laine, Sjöros, Garthwaite, Honka, Löyttyniemi, Eskola, Saarenhovi, Kallio, Koivumäki, Vähä-Ypyä, Sievänen, Vasankari, Hirvonen, Laitinen, Houttu, Kalliokoski, Saunavaara, Knuuti and Heinonen.)

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., (© 2024. The Author(s).)

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 (V̇o 2max ; 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 [β = 0.35 (95% confidence interval: 0.04, 0.67)], impaired insulin-stimulated MetFlex (ΔRER) [β=-0.41 (-0.72, -0.09)], and lower fasting FATox [β=-0.36 (-0.67, -0.04)]. Standing associated with lower fasting RER [β=-0.32 (-0.62, -0.02)]. Higher standing time and steps/day associated with higher fasting FATox [β = 0.31 (0.01, 0.61), and β = 0.26 (0.00, 0.53)]. Light-intensity and total PA associated with better insulin-stimulated MetFlex [β = 0.33 (0.05, 0.61)], and β = 0.33 (0.05, 0.60)]. Higher V̇o 2max associated with higher CHOox during maximal exercise [β = 0.81 (0.62, 1.00)], as well as during insulin stimulation [β = 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.

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, 10 10 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.

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 [ 18 F]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.

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&#95;7&#95; 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&#95;1&#95;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&#95;1&#95;39BFAA in late pregnancy (FDR < 0.25). α-Diversity or β-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., (© 2023. The Author(s).)

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 (VO 2max ) 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 VO 2max statistically significantly (group × time p > 0.05). Maximal absolute power output (W max ) 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] W max /kg FFM , p = 0.036). Finally, the changes in daily step count correlated positively with the changes in VO 2max 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 VO 2max in adults with metabolic syndrome. However, succeeding in increasing daily step count may increase VO 2max ., (© 2023 The Authors. Scandinavian Journal of Medicine & Science In Sports published by John Wiley & Sons Ltd.)

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., (© 2023. The Author(s).)

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 VO 2 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 (β = -0.374), standing (β = 0.376), steps (β = 0.351), and VO 2 max (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.)

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., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Sports Medicine.)

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., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objective: To investigate whether alterations in brain glucose uptake (BGU), insulin action in the brain-liver axis and whole-body insulin sensitivity occur in young adults in pre-obese state., Methods: Healthy males with either high risk (HR; n = 19) or low risk (LR; n = 22) for developing obesity were studied with [18F]fluoro-d-glucose ([18F]FDG)-positron emission tomography during hyperinsulinemic-euglycemic clamp. Obesity risk was assessed according to BMI, physical activity and parental overweight/obesity and type 2 diabetes. Brain, skeletal muscle, brown adipose tissue (BAT), visceral adipose tissue (VAT) and abdominal and femoral s.c. adipose tissue (SAT) glucose uptake (GU) rates were measured. Endogenous glucose production (EGP) was calculated by subtracting the exogenous glucose infusion rate from the rate of disappearance of [18F]FDG. BGU was analyzed using statistical parametric mapping, and peripheral tissue activity was determined using Carimas Software imaging processing platform., Results: BGU was higher in the HR vs LR group and correlated inversely with whole-body insulin sensitivity (M value) in the HR group but not in the LR group. Insulin-suppressed EGP did not differ between the groups but correlated positively with BGU in the whole population, and the correlation was driven by the HR group. Skeletal muscle, BAT, VAT, abdominal and femoral SAT GU were lower in the HR group as compared to the LR group. Muscle GU correlated negatively with BGU in the HR group but not in the LR group., Conclusion: Increased BGU, alterations in insulin action in the brain-liver axis and decreased whole-body insulin sensitivity occur early in pre-obese state.

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 (β=-0.404 to -0.372, 95% CI: -0.704 to -0.048), HOMA-IR (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.

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).)

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., (© 2022. The Author(s).)

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]), HbA 1c (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., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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, 10 10 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., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

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.

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., (© 2021. The Author(s).)

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 CB 1 receptors (CB 1 Rs) 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 [ 18 F]FDG during hyperinsulinemic euglycemic clamp, MORs were quantified with [ 11 C]carfentanil and CB 1 Rs with [ 18 F]FMPEP-d 2 ., 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 CB 1 Rs (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., (© 2021. The Author(s).)

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. VO 2 max (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 VO 2 max 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., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: If a pregnant woman is overweight, this can evoke metabolic alterations that may have health consequences for both mother and child., Methods: Pregnant women with overweight/obesity (n = 358) received fish oil+placebo, probiotics+placebo, fish oil+probiotics or placebo+placebo from early pregnancy onwards. The serum metabolome was analysed from fasting samples with a targeted NMR-approach in early and late pregnancy. GDM was diagnosed by OGTT., Findings: The intervention changed the metabolic profile of the women, but the effect was influenced by their GDM status. In women without GDM, the changes in nine lipids (FDR<0.05) in the fish oil+placebo-group differed when compared to the placebo+placebo-group. The combination of fish oil and probiotics induced changes in more metabolites, 46 of the lipid metabolites differed in women without GDM when compared to placebo+placebo-group; these included reduced increases in the concentrations and lipid constituents of VLDL-particles and less pronounced alterations in the ratios of various lipids in several lipoproteins. In women with GDM, no differences were detected in the changes of any metabolites due to any of the interventions when compared to the placebo+placebo-group (FDR<0.05)., Interpretation: Fish oil and particularly the combination of fish oil and probiotics modified serum lipids in pregnant women with overweight or obesity, while no such effects were seen with probiotics alone. The effects were most evident in the lipid contents of VLDL and LDL only in women without GDM., Funding: State Research Funding for university-level health research in the Turku University Hospital Expert Responsibility Area, Academy of Finland, the Diabetes Research Foundation, the Juho Vainio Foundation, Janssen Research & Development, LLC., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

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.

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: We investigated the impact of fish oil and/or probiotics on serum and vaginal inflammatory and metabolic proteins and their relation to the onset of gestational diabetes mellitus (GDM)., Methods: Overweight/obese pregnant women received fish oil + placebo, probiotics + placebo, fish oil + probiotics or placebo + placebo from early pregnancy until six months postpartum (fish oil: 1.9 g docosahexaenoic acid and 0.22 g eicosapentaenoic acid; probiotics: Lactobacillus rhamnosus HN001 and Bifidobacterium animalis ssp. lactis 420, 10 10 colony-forming units each). Serum high sensitivity C-reactive protein (hsCRP) and serum/vaginal (s/v) phosphorylated insulin-like growth factor binding-protein-1 (phIGFBP-1), IGFBP-1 and matrix metalloproteinase 8 (MMP-8) were analyzed. GDM was diagnosed according to 2 h 75 g OGTT., Results: The intervention had no impact on the change in proteins during pregnancy. Nevertheless, s-MMP-8 decreased and s-IGFBP-1 increased more in obese than in overweight women in the fish oil + probiotics group, while a decrease in s-MMP-8 was seen in obese women and an increase was seen in overweight women in the probiotics + placebo group. The late pregnancy s-phIGFBP-1 was higher in women who developed GDM in fish oil + probiotics-group compared to fish oil + placebo-group. The concentrations of s-phIGFBP-1 (635.9 ± 315.3 ng/mL vs. 753.2 ± 335.1 ng/mL, p = 0.005) and s-IGFBP-1 (3.78 ± 0.72 ng/mL vs. 3.96 ± 0.69 ng/mL, p = 0.042) were lower in early pregnancy in women who developed GDM than in women remaining healthy., Conclusions: The intervention per se had no impact on the proteins, but obesity and GDM may modify the effect. IGFBPs may affect the development of GDM.

Objective: Whether the presence of gestational diabetes (GDM) and its treatment mode influence the serum metabolic profile in women with overweight or obesity was studied., Methods: The serum metabolic profiles of 352 women with overweight or obesity participating in a mother-infant clinical study were analyzed with a targeted NMR approach (at 35.1 median gestational weeks). GDM was diagnosed with a 2-hour 75-g oral glucose tolerance test., Results: The metabolomic profile of the women with GDM (n = 100) deviated from that of women without GDM (n = 252). Differences were seen in 70 lipid variables, particularly higher concentrations of very low-density lipoprotein particles and serum triglycerides were related to GDM. Furthermore, levels of branched-chain amino acids and glycoprotein acetylation, a marker of low-grade inflammation, were higher in women with GDM. Compared with women with GDM treated with diet only, the women treated with medication (n = 19) had higher concentrations of severalizes of VLDL particles and their components, leucine, and isoleucine, as well as glycoprotein acetylation., Conclusions: A clearly distinct metabolic profile was detected in GDM, which deviated even more if the patient was receiving medical treatment. This suggests a need for more intense follow-up and therapy for women with GDM during pregnancy and postpartum to reduce their long-term adverse health risks., (© 2020 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society (TOS).)

Background & Aims: Aberrations in body composition are expected in children suffering from chronic inflammatory conditions. The objective is to examine whether children with inflammatory bowel disease (IBD: Crohn's disease and ulcerative colitis), coeliac disease, asthma and juvenile idiopathic arthritis (JIA) have an altered body composition as compared to healthy children., Methods: A systematic review, registered in Prospero (registration number: CRD42018107645), was conducted according to PRISMA guidelines. We conducted a search of three databases, Pubmed, Cochrane and Scopus. An assessment of the quality of the study was performed., Results: Data from 50 studies, 32 with IBD, 8 with coeliac disease, 2 with asthma and 8 with JIA, involving 2399 children were selected for review after applying the eligibility criteria. In all but 4 studies, children with Crohn's disease exhibited decreased amounts of fat mass and fat free mass. Reductions in fat mass were also evident in studies in children with coeliac disease. It is uncertain whether body composition is altered in children with asthma or JIA., Conclusions: Children with Crohn's disease manifest with lowered adiposity and lean mass and therefore are likely to be at risk for suffering malnutrition-related clinical complications. Apart from Crohn's disease, data examining body composition in children with chronic inflammatory conditions are scarce and there is a paucity of reports examining the relationship between inflammation and body composition. Interpretation of the current study results is hampered by the low quality of the studies and due to the fact that the analyses have been habitually secondary outcomes., Competing Interests: Conflict of interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Lower level of insulin-like growth factor-binding protein (IGFBP-1) has been observed in insulin resistance, while higher level of matrix metalloproteinase-8 (MMP-8) has been linked to obesity. The aim here was to study in overweight and obese women, typically manifesting with insulin resistance, whether IGFBP-1 and MMP-8 are related to and reflect systemic low-grade inflammation, metabolism and diet. Fasting serum from overweight and obese pregnant women (n = 100) in early pregnancy were analysed for IGFBP-1, phosphorylated IGFBP-1 (phIGFBP-1) and MMP-8. High-sensitivity CRP and GlycA were used as markers for low grade inflammation. GlycA and lipids were quantified using NMR. IGFBP-1 associated negatively with GlycA, evidenced by higher concentrations in the lowest quartile (median 1.53 (IQR 1.45-1.72)) compared to the highest (1.46 (1.39-1.55)) (P = 0.03). Several lipid metabolites, particularly HDL-cholesterol, correlated inversely with phIGFBP-1 (FDR<0.1). Nutritional status and diet contributed to the levels of IGFBP-1, demonstrated as an inverse correlation with maternal weight (Spearman r = -0.205, P = 0.04) and dietary intake of vitamin A (r = -0.253, P = 0.014) and a direct correlation with dietary intake of polyunsaturated fatty acids (Spearman r = 0.222, P = 0.03). MMP-8 correlated inversely with pyridoxine (r = -0.321, P = 0.002) and potassium (r = -0.220, P = 0.033). Maternal serum IGFBP-1 may contribute to maternal lipid metabolism in overweight and obese women during early pregnancy. These findings may be of importance in identification of metabolic disturbances preceding the adverse metabolic outcomes in pregnancy., (© 2020 The Authors.)

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.

The current scientific literature proposes that both the amount and type of dietary fat modulate homeostasis of the gut microbiota; disturbances in homeostasis may have metabolic consequences with potentially serious clinical manifestations. The evidence for interactions between dietary fat and gut microbiota has been mostly derived from animal studies, but there is now also evidence emerging from human studies. We will review the current literature on how dietary fat influences the gut microbiota, particularly focusing on the type of fat. Mechanisms detailing how this crosstalk may impact on host metabolism and health will also be discussed. Some studies have reported somewhat controversial findings and therefore we will evaluate critically which possible aspects should be considered when interpreting current and planning further studies to explore the diet-microbiota crosstalk and its metabolic and clinical implications for the host., (Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

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., (Copyright © American Society for Nutrition 2019.)

Objective: To assess whether the risk of gestational diabetes mellitus (GDM) may be lowered and glucose metabolism improved by daily administration of fish oil and/or probiotic supplements in overweight and obese pregnant women., Research Design and Methods: We randomized in a double-blind manner 439 women (mean 13.9 ± 2.1 gestational weeks [gw]) into four intervention groups: fish oil + placebo, probiotics + placebo, fish oil + probiotics, and placebo + placebo. Fish oil (1.9 g docosahexaenoic acid and 0.22 g eicosapentaenoic acid) and probiotic supplements ( Lactobacillus rhamnosus HN001 and Bifidobacterium animalis ssp. lactis 420, 10 10 colony-forming units each) were provided for daily consumption from randomization beyond delivery. Primary outcomes were the incidence of GDM diagnosed with oral glucose tolerance test targeted at 24-28 gw and the change in fasting glucose between randomization and late pregnancy (mean 35.2 ± 0.9 gw). Insulin concentration, insulin resistance HOMA2-IR index, and pregnancy outcomes were determined, as were adverse effects related to the intervention. Analyses were by intent to treat., Results: No differences were found among the intervention groups in the maternal and neonatal pregnancy outcomes or side effects related to the intervention ( P > 0.05). The proportion of women with GDM (94 of 377; fish oil + placebo, 23 of 96, 24.0%; probiotics + placebo, 25 of 99, 25.3%; fish oil + probiotics, 26 of 91, 28.6%; and placebo + placebo, 20 of 91, 22.0%) and the change in glucose, insulin, or HOMA2-IR ( n = 364) did not differ among the intervention groups ( P > 0.11 for all comparisons)., Conclusions: An intervention with fish oil and/or probiotics during pregnancy seemed to be both safe and well tolerated but conferred no benefits in lowering the risk of GDM or improving glucose metabolism in overweight and obese women., (© 2019 by the American Diabetes Association.)

Background: Overweight and obesity may predispose women to clinical complications during their pregnancy. We hypothesize that a higher degree of overweight status is related to a range of aberrations in biomarkers already in early pregnancy. Our objective was to investigate whether intestinal microbiota, serum metabolic and inflammatory profiles differ in relation to the degree of overweight status in pregnant women., Methods: This study investigated 52 overweight and 47 obese pregnant women in early pregnancy. Fecal samples were analyzed for intestinal microbiota composition by 16S ribosomal RNA gene sequencing and Qiime pipeline. Circulating serum metabolites, including lipids, amino acids and GlycA, a marker of low-grade inflammation, were analyzed by NMR metabolomics and hsCRP was quantified by immunoassay. Serum zonulin levels were analyzed to depict intestinal permeability by Zonulin ELISA kit and LPS activity for endotoxemia by Limulus amebocyte lysate assay. The analyses were adjusted for multiple comparisons using Benjamini-Hochberg procedure for false discovery rate controlling., Results: The relative abundance of bacterial family Prevotellaceae (adjusted P = 0.19) and markers of low-grade inflammation, hsCRP (P = 0.0015) and GlycA (P < 0.001) and three branched chain amino acids (isoleucine, adjusted P = 0.024; leucine, adjusted P = 0.026; valine, adjusted P = 0.10) and one aromatic amino acid (phenylalanine, adjusted P = 0.050) and concentrations of several VLDL particles and lipid measures in several VLDL particles were higher in obese pregnant women compared to their overweight pregnant counterparts (adjusted P < 0.12). In contrast, lipid measures in a few HDL particles and many fatty acids were lower in obese compared to overweight pregnant women (adjusted P < 0.12)., Conclusions: The detected alterations in intestinal microbiota and metabolic and inflammatory profiles related to obesity status may offer new alternative tools to supplement standard clinical measures to predict the risk for metabolic alterations during the early phase of pregnancy., (Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)