NW Group Research Articles

Metabolic flexibility during normal pregnancy allows appropriate adaptation during gestation independently of BMI.

Overweight and obesity in reproductive-age women hasten the development of insulin resistance and increase risk for deterioration of pregnancy metabolism. These pregnancy-associated metabolic changes are similar to those of the metabolic syndrome. Thus, some metabolic flexibility must allow appropriate adaptation to the metabolic load that pregnancy imposes. We evaluated metabolic flexibility during uncomplicated pregnancy in women with pre-gestational normal weight or overweight. In 20 women with singleton pregnancies, pre-pregnancy BMI was categorized as normal-weight (Nw) or overweight (Ow). The women were seen quarterly, and fasting and postprandial blood samples were collected at each visit. Indirect fasting and/postprandial calorimetry was performed to evaluate metabolic flexibility (Δrespiratory quotient (RQ)=RQpostprandial - RQfasting). In the first trimester, metabolic flexibility was lower in the Ow group compared to the Nw group (0.031±0.0131 vs 0.077±0.018, respectively) without a statistically significant difference (p=0.053). In the second trimester, the Ow group was significantly more flexible than the Nw group (0.190±0.016 vs 0.077±0.015, respectively (p=0.004)). For the third trimester, the Ow and Nw groups did not differ in metabolic flexibility (0.074±0.013 vs 0.087±0.021, respectively) (p=0.40). The most influential variables for metabolic flexibility during pregnancy were lactate, leptin, β-hydroxybutyrate, glycerol, aromatic amino acids, medium and long chain acylcarnitine's. Our findings indicate that metabolic flexibility changes throughout pregnancy, independently of pre-pregnancy BMI. These changes maintain metabolic homeostasis between the mother and foetus, allowing for appropriate adjustments during pregnancy.

Effects of an unsupervised Nordic walking intervention on cognitive and physical function among older women engaging in volunteer activity

BackgroundNordic walking (NW) has been reported as a safe and effective exercise mode. However, the effects of NW on cognitive function are unknown. This study examined the effects of an unsupervised NW intervention on cognitive and physical function among older women engaging in volunteering. MethodsForty-seven women aged ≥70 years were enrolled and assigned into three groups (NW (n = 16); walking (n = 19); control group (n = 12)) based on residential areas. Participants in NW and walking groups received a pedometer and recorded daily step counts. The NW group received poles and 2 h of NW instruction. Participants were encouraged to perform the exercise individually more than once a week during the 3-month intervention. As baseline and follow-up assessments, cognitive function (Montreal Cognitive Assessment [MoCA-J] and Trail Making Test), physical function (handgrip strength, walking speed, balance ability, the Timed Up and Go test, and functional capacity), and objective physical activity were evaluated. ResultsIn the NW group, physical activity, maximal walking speed, and MoCA-J scores were improved during the intervention period. In the walking group, physical activity was increased after the intervention. Analysis of covariance showed that maximal walking speed among the NW group significantly improved compared with the walking group. Sub-group analysis of participants who exercised more than once a week showed that handgrip strength, gait speed, and MoCA-J scores were significantly improved in the NW compared with the walking group. ConclusionNW intervention improved cognitive and physical function compared with simple walking among older women.

Low Body Mass Index Levels and Idiopathic Scoliosis in Korean Children: A Cross-Sectional Study.

Background: The prevalence of idiopathic scoliosis is rapidly increasing in Korean children, but research on the disorder is limited compared to that in other countries. Accordingly, in the present study, we aimed to investigate the relationship between idiopathic scoliosis and body mass index (BMI) levels in Korean children. Methods: This cross-sectional study enrolled elementary school students and middle school first graders in the Capital Area in Korea. The participants underwent body composition measurements and screening for idiopathic scoliosis. Idiopathic scoliosis was defined as a Cobb angle of ≥10°. The students were classified into three groups—the severely underweight (SUW: BMI < 16 kg/m2) group, the underweight group (UW: 16 ≤ BMI < 18.5 kg/m2), and the normal weight group (NW: 18.5 ≤ BMI < 25 kg/m2) to compare the risk of idiopathic scoliosis across BMI levels. Results: The final cohort comprised 1375 participants. The odds ratio (OR) of idiopathic scoliosis was 0.69 (95% confidence interval (CI): 0.50–0.94) and 0.66 (95% CI: 0.49–0.89) for the UW and the NW groups, respectively, with the SUW group as the reference. This shows that the risk decreased significantly by 31% and 34% in the UW and the NW groups, respectively. After controlling for age and sex, the corresponding ORs were 0.72 (95% CI: 0.52–0.98) and 0.70 (95% CI: 0.51–0.96), and the risk significantly decreased by 28% and 30% in the UW and the NW groups, respectively. Conclusions: Low body weight is closely associated with spinal deformity and idiopathic scoliosis.

Proteomic analysis of overweight/obesity and related abnormal glucose and lipid metabolism caused by phlegm-dampness retention

To investigate the proteomic characteristics of overweight/obesity and related abnormal glucose and lipid metabolism caused by phlegm-dampness retention to identify related biomarkers. Seventy-one subjects were enrolled in the study. We assessed blood glucose, blood lipids, body mass index (BMI), and phlegm-dampness pattern, which was confirmed by a traditional Chinese medicine clinician. Of the participants, we included healthy participants with normal weight (NW, n = 23), overweight/obese participants with normal metabolism (ONM, n = 19), overweight/obese participants with pre-diabetes (OPD, n = 12), and overweight/obese participants with marginally-elevated blood lipids (OML, n = 17). Among them, the ONM, OPD, and OML groups were diagnosed with phlegm-dampness pattern. The data-independent acquisition (DIA) method was first used to analyze the plasma protein expression of each group, and the relevant differential proteins of each group were screened. The co-expressed proteins were evaluated by Venn analysis. The pathway analyses of the differential proteins were analyzed using Ingenuity Pathway Analysis (IPA) software. Parallel reaction monitoring (PRM) was used to verify the differential and common proteins in each group. After comparing ONM, OPD, and OML groups with NW group, we identified the differentially expressed proteins (DEPs). Next, we determined the DEPs among OPD, OML, and ONM groups. Using Venn analysis of the DEPs in each group, 24 co-expressed proteins were screened. Two co-expressed proteins were verified by PRM. IPA analysis showed that pathways including LXR/RXR activation, acute phase response signaling, and FXR/RXR activation were common to all three groups of phlegm-damp overweight/obesity participants. However, the activation or inhibition of these pathways was different among the three groups. Participants with overweight/obesity have similar proteomic characteristics, though each type shows specific proteomic characteristics. Two co-expressed proteins, VTN and ORM1, are potential biomarkers for glucose and lipid metabolism diseases with overweight/obesity caused by phlegm-dampness retention.

Modulatory Effect of Probiotic Lactobacillus rhamnosus PB01 on Mechanical Sensitivity in a Female Diet-Induced Obesity Model.

Obese animals and humans demonstrate higher sensitivity to pain stimuli. Among the endogenous factors prompting obesity, the intestinal microbiota has been proposed to influence responsiveness to pain. The beneficial effects of probiotics on obesity are well documented, whereas data on their analgesic efficacy is minimal. The protective effect of probiotics on nociception in diet-induced obese male mice has been previously demonstrated, but the sex differences in pain sensitivity and analgesic response do not allow for the generalization of these findings to the female gender. Hence, this study aimed at investigating the potential effects of oral probiotic supplementation on mechanical pain thresholds in female diet-induced obese mice compared with controls. Thirty-two adult female mice (N=32) were randomly divided into two groups receiving standard (normal-weight group; NW) or high-fat diet (diet-induced obesity; DIO). All rats received a single daily dose (1 × 109 CFU) of probiotics (Lactobacillus rhamnosus PB01, DSM14870) for four weeks by gavage. Mechanical pain thresholds were recorded by an electronic von Frey device at baseline, at the end of weeks 2, 4, 6, and 8 in both DIO and NW groups with and without consumption of probiotics. Blood samples were obtained for the measurement of lipid profile and reproductive hormone levels. Bodyweight was considerably lower (P < 0.001) in groups supplied with probiotics than groups without probiotics. Pressure pain threshold values showed a significant (P < 0.001) increase (reduced pain sensitivity) following probiotic supplementation, proposing a modulatory effect of probiotics on mechanical sensory circuits and mechanical sensitivity, which might be a direct consequence of weight loss or an indirect result of the probiotics' anti-inflammatory properties. Understanding the precise underlying mechanism for the effect of probiotics on weight loss and mechanical pain sensitivity seen in this study warrants further investigation.

Abstract 075: Differences In Body Composition At Baseline And In Response To Exercise Training By Metabolic Health And Weight Status

Background: Body composition is known to differ across metabolic health and weight phenotypes. Regular exercise improves body composition, yet little is known about differences in exercise response across metabolic health and weight phenotypes. Methods: Normal weight (n=376) and overweight/obese (OWOB) adults (n=456) from the HERITAGE Family Study (56% female, 38% Black) completed a 20-week endurance training program. Four groups based on baseline BMI and metabolic risk were created: metabolically healthy normal weight, MHNW; metabolically unhealthy normal weight, MUNW; metabolically healthy OWOB, MHO; and metabolically unhealthy OWOB, MUO. Unhealthy was defined as having ≥2 metabolic syndrome components. General linear models tested for differences in baseline and change in measures of body composition (fat mass [FM], fat-free mass [FFM], % body fat [%BF], visceral fat) after adjusting for age, sex, and ethnicity (and baseline value in change models). Results: Table 1 shows adjusted mean baseline and change in body composition values by group. Baseline body composition tended to track with weight status, with NW adults having lower FM, %BF, and visceral fat compared to obese adults (p&lt;0.05), regardless of metabolic health. However, the MHO group had lower baseline values of these traits compared to MUO (p&lt;0.05). Body composition measures significantly improved with exercise training in all groups, however, the magnitude of change differed between groups. For example, both NW groups had larger decreases in %BF compared to the obese groups, with MUNW showing the largest decrease. Conversely, MHNW showed the largest decrease in visceral fat, which was greater than both obese groups, but change in visceral fat was similar between MHO and MUNW. Conclusions: Normal weight adults tended to have better body composition profiles at baseline and larger improvements with exercise compared to obese adults, regardless of metabolic health. Within weight groups, body composition improved regardless of metabolic health status.

Human Milk Exosomal MicroRNA: Associations with Maternal Overweight/Obesity and Infant Body Composition at 1 Month of Life.

Among all the body fluids, breast milk is one of the richest sources of microRNAs (miRNAs). MiRNAs packaged within the milk exosomes are bioavailable to breastfeeding infants. The role of miRNAs in determining infant growth and the impact of maternal overweight/obesity on human milk (HM) miRNAs is poorly understood. The objectives of this study were to examine the impact of maternal overweight/obesity on select miRNAs (miR-148a, miR-30b, miR-29a, miR-29b, miR-let-7a and miR-32) involved in adipogenesis and glucose metabolism and to examine the relationship of these miRNAs with measures of infant body composition in the first 6 months of life. Milk samples were collected from a cohort of 60 mothers (30 normal-weight [NW] and 30 overweight [OW]/obese [OB]) at 1-month and a subset of 48 of these at 3 months of lactation. Relative abundance of miRNA was determined using real-time PCR. The associations between the miRNAs of interest and infant weight and body composition at one, three, and six months were examined after adjusting for infant gestational age, birth weight, and sex. The abundance of miR-148a and miR-30b was lower by 30% and 42%, respectively, in the OW/OB group than in the NW group at 1 month. miR-148a was negatively associated with infant weight, fat mass, and fat free mass, while miR-30b was positively associated with infant weight, percent body fat, and fat mass at 1 month. Maternal obesity is negatively associated with the content of select miRNAs in human milk. An association of specific miRNAs with infant body composition was observed during the first month of life, suggesting a potential role in the infant’s adaptation to enteral nutrition.

Increase in CD5L expression in the synovial membrane of knee osteoarthritis patients with obesity.

IntroductionObesity appears to be a powerful risk factor for the development of knee osteoarthritis (KOA), but the mechanisms of this are not fully understood. CD5L is expressed in tissue macrophages and is increased in obese mice. We hypothesized that CD5L expression is increased in the synovial membrane (SM) of obese KOA patients. Here, we investigated CD5L expression in the SM of these patients.Material and methodsNinety KOA patients (26 males, 64 females) were allocated to one of three groups based on body mass index (BMI): normal weight (NW, < 25 kg/m²), overweight (OW, 25-29.99 kg/m²) and obese (OB, ≥ 30 kg/m²), according to the World Health Organization BMI classification (each n = 30). Expression of CD5L in SM among the groups was compared using real-time polymerase chain reaction. To investigate CD5L-expressing cells in SM, CD14+ (macrophage fraction) and CD14– (fibroblast fraction) cells were separated from the SM.ResultsCD5L expression was significantly higher in the OB group than in the NW and OW groups (p < 0.001). CD5L expression was observed in the CD14+ fraction but not in the CD14– fraction.ConclusionsCD5L is highly expressed in the SM of KOA patients with obesity. Further investigation is required to identify the role of CD5L in the relationship between KOA pathology and obesity.

Nordic Walking and Free Walking Improve the Quality of Life, Cognitive Function, and Depressive Symptoms in Individuals with Parkinson's Disease: A Randomized Clinical Trial.

Nordic walking’s (NW) degree of effectiveness regarding health-related parameters in people with Parkinson’s Disease (PD) is a subject of debate. While NW seems to improve functionality, a clear non-motor benefit has not been demonstrated. The aim of this randomized controlled trial was to compare the effects of 9-week NW and free walking (FW) training programs on quality of life, cognitive function, and depressive symptoms in individuals with PD. Thirty-three people with PD, (Hoehn and Yahr 1–4) were randomized into two groups: NW (n = 16) and FW (n = 17). We analyzed quality of life, cognitive function, depressive symptoms, and motor symptoms. Significant improvements were found in the overall, physical, psychological, social participation, and intimacy domains of quality of life, as well as in cognitive function and depressive symptoms for both groups. Only the NW group showed improvement in the autonomy domain. Individuals with PD had a similar enhancement of non-motor symptoms after walking training, with or without poles. However, the NW group showed a more significant improvement in the autonomy domain, strengthening the applied and clinical potential of NW in people with PD. Future studies are needed to determine the efficacy of walking training without poles in subjects with PD.

Evaluating the Effects of Different Sleep Supplement Modes in Attenuating Metabolic Consequences of Night Shift Work Using Rat Model.

PurposeTo study the effects of chronic-simulated night shift work using the rat model and examines if a particular sleep supplement mode could be better in alleviating the effects.MethodsThe male Wistar rats were randomly divided into the control (CTL: 8 rats) and night shift work (NW: 24 rats) groups of rats. Based on the sleep supplement strategy, the NW group was further segregated into three subgroups (8 rats each); late sleep supplement group (LSS), early sleep supplement group (ESS), and intermittent sleep supplement group (ISS). Sleep deprivation was achieved using the standard small-platform-over water method. Parameters such as animal body weight and food intake were measured daily. The intraperitoneal glucose tolerance test, fasting plasma insulin concentration, insulin resistance index and insulin sensitivity were measured twice, in the 4th and 8th weeks of the study. Plasma corticosterone concentration and pathological changes in islets (insulitis) were measured at the end of the 8th week.ResultsIn NW group, night work resulted in a gain of body weight and albeit lower than that of the CTL group. NW rats also had higher food intake, showed impaired glucose metabolism and higher plasma corticosterone concentration. The sleep supplement experiments suggested that compared to the other modes, intermittent sleep supplement had significantly low changes in the body weight, glucose metabolism and the islet cells.ConclusionSimilar to previous studies, we also found that night shift work adversely impacts the body weight and glucose metabolism in rats. However, upon evaluating different sleep supplement strategies, we found the intermittent sleep supplement strategy to be most effective.

Different Amounts of Water Supplementation Improved Cognitive Performance and Mood among Young Adults after 12 h Water Restriction in Baoding, China: A Randomized Controlled Trial (RCT).

Water is indispensable to keeping the functions of the human body working properly, including that of the brain. The purpose of this research was to explore the impacts of water supplementation on cognitive performance and mood, and to determine the optimum amount of water to alleviate detriments of dehydration after 12 h water restriction. A randomized controlled trial was implemented among 64 young adults from Baoding, China. Fasting overnight for 12 h, and at 8:00 a.m. on day 2, osmolality of first morning urine and blood, cognitive performance, and mood were assessed as the dehydration test. Then, participants were randomly separated into four groups: water supplementation groups (WS groups 1, 2, and 3 with 500, 200, and 100 mL purified water, respectively) and no water supplementation group (NW group). Participants in WS groups were instructed to drink the water within 10 min, while those in NW group drank no water. After 90 min, the same measurements were taken as the rehydration test. There was significant interaction between TIME and VOLUME in thirst when comparing dehydration with rehydration tests (F = 6.172, p = 0.001). Significant thirst reductions were found in WS group 1 and WS group 2 (p = 0.003; p = 0.041), and a significant increase was found in the NW group (p = 0.039). In the rehydration test, significant interactions between TIME and VOLUME were found in scores of anger, fatigue, and TMD (total mood disturbance) (F = 3.815, p = 0.014; F = 10.429, p < 0.001; F = 5.246, p < 0.001), compared to the dehydration test. Scores of anger were only decreased in WS group 2 (p = 0.025), and scores of fatigue and TMD decreased in WS group 1 and WS group 2 (all p < 0.05). Significant interaction between TIME and VOLUME was only found for operation span test scores (F = 2.816, p = 0.047), with scores being only higher in WS group 1 in the rehydration test compared to the dehydration test (p = 0.003). Comparing WS group 1 and WS group 2, scores of thirst, fatigue, and TMD did not differ significantly (p > 0.05). Water supplementation improved working memory and attenuated anger, fatigue, and TMD. A small amount of water (200 mL) was sufficient to attenuate thirst, anger, fatigue, and TMD of young adults, but the larger volume (500 mL) appeared to be necessary to improve working memory. The amount of 500 mL was the optimum volume to improve the cognitive performance and mood among young adults.

A Real-World Evaluation of the Long-Term Safety and Efficacy of Infliximab in the Treatment Moderate-to-Severe Psoriasis.

IntroductionPsoriasis is a chronic immune-mediated inflammatory skin disease that occurs in 2.5–3.5% of the general population. Infliximab (INF), a TNF-α inhibitor biologic agent, is a long-standing efficacious treatment for psoriasis; however, not all patients sustain a long-term response (LTR) because of a number of factors including antibody production. There is a paucity of studies assessing infliximab efficacy over a period ≥ 5 years.MethodsA retrospective cohort chart review of our clinic patients who had undergone ≥ 5 years of treatment with infliximab for chronic plaque psoriasis was performed. The following variables were recorded and analyzed with the Fisher exact test: age, sex, body mass index ([BMI]; normal weight [NW], overweight [OW], obese [OB]), changes in infliximab strength (dose or frequency), concomitant systemic therapy, and side effects. Clinical improvement was assessed by comparing the total body surface area (tBSA) affected by psoriasis before and after treatment.ResultsThere was a significant difference in likelihood of achieving LTR between the NW, OW and OB groups (p = 0.044). Non-normal-weight patients (OW + OB) were significantly more likely to achieve and sustain LTR than NW patients (OR 9.07, p = 0.020). There were no other significant associations for the other evaluated variables.LimitationsPatients who began treatment with infliximab before 2009 (prior to the use of the clinic’s electronic medical record) were excluded. The Psoriasis Area and Severity Index (PASI) was not available for this study.ConclusionSurprisingly, patients who are overweight or obese are more likely to obtain long-term clinical benefit in their psoriasis symptoms with infliximab therapy than patients who are normal weight.Electronic supplementary materialThe online version of this article (10.1007/s13555-020-00436-1) contains supplementary material, which is available to authorized users.

Physical Activity Measured by Accelerometry in Mozambican Older Adult Women Attending a Regular Exercise Program.

Time spent in different Physical Activity (PA) Intensities of 72 Mozambican older adult women (67 ± 7years old) was assessed by means of triaxial accelerometers for 7 consecutive days, and participants were stratified based on their body mass index, as being normal weight (NW, n = 23); overweight (n = 16); or obese (OB, n = 33). Overall, most daily time was spent in sedentary activities (614 ± 111min or 69.1%) and light PA (181 ± 56min or 20.2%). On average, moderate to vigorous PA (MVPA) was performed during 10.6% of the day (93 ± 44min). Time spent in MVPA was significantly higher in the NW compared to OB category (112.8 ± 51.5 vs. 81.0 ± 36.3; p = .021). The overweight group did not differ in time spent in MVPA when compared to NW and OB group. Overall, 75% of the participants spent more than 60min a day in MVPA (NW: 83%; overweight: 81%; OB: 67%). Pearson's correlation between body mass index and total MVPA controlling for age was -.39 (p < .001). It was concluded that Mozambican older adult women living in urban and rural areas of Maputo province engaged in relatively high Physical Activity Intensities compared with individuals of similar ages in high-income countries, regardless of their nutritional status.

Identification of pathognomonic purine synthesis biomarkers by metabolomic profiling of adolescents with obesity and type 2 diabetes.

The incidence of type 2 diabetes is increasing more rapidly in adolescents than in any other age group. We identified and compared metabolite signatures in obese children with type 2 diabetes (T2D), obese children without diabetes (OB), and healthy, age- and gender-matched normal weight controls (NW) by measuring 273 analytes in fasting plasma and 24-hour urine samples from 90 subjects by targeted LC-MS/MS. Diabetic subjects were within 2 years of diagnosis in an attempt to capture early-stage disease prior to declining renal function. We found 22 urine metabolites that were uniquely associated with T2D when compared to OB and NW groups. The metabolites most significantly elevated in T2D youth included members of the betaine pathway, nucleic acid metabolism, and branched-chain amino acids (BCAAs) and their catabolites. Notably, the metabolite pattern in OB and T2D groups differed between urine and plasma, suggesting that urinary BCAAs and their intermediates behaved as a more specific biomarker for T2D, while plasma BCAAs associated with the obese, insulin resistant state independent of diabetes status. Correlative analysis of metabolites in the T2D signature indicated that betaine metabolites, BCAAs, and aromatic amino acids were associated with hyperglycemia, but BCAA acylglycine derivatives and nucleic acid metabolites were linked to insulin resistance. Of major interest, we found that urine levels of succinylaminoimidazole carboxamide riboside (SAICA-riboside) were increased in diabetic youth, identifying urine SAICA-riboside as a potential biomarker for T2D.

156-LB: Effect of Maternal Obesity and GDM on Children’s Obesity and Fat Distribution

Background: Women with obesity or gestational diabetes (GDM) and their children are at risk for type 2 diabetes. Given that obesity and fat distribution are correlated with insulin resistance, we examined whether there are differences in total adiposity and fat distribution among women who were lean (NW) or obese (Ob) with no GDM history, verses women with prior GDM, and their children. We hypothesized that dyads in the GDM group would have greater adiposity and more centralized fat distribution compared to dyads in the NW and Ob groups. Methods: Mother-child dyads were enrolled 4-10 years after a pregnancy complicated by GDM (N=73), or without GDM and NW (N=76) or Ob (N=76). Body weight, height, and anthropometric measures of adiposity were collected. ANCOVA were used to assess group differences in BMI, BMIz (in children), sum of skinfolds (SS), waist to hip ratio (WHR), and central (suprailiac + subscapular) to peripheral (thigh + tricep) skinfold ratio (CvP). Models were adjusted for age and race for mothers, along with tanner stage and sex for children. Results: Women with prior GDM had greater BMI and SS compared to women in the NW group (P&amp;lt;0.0001), but did not differ from Ob. Despite similar total adiposity for GDM and Ob groups, the GDM group had greater WHR and CvP as compared to Ob (P&amp;lt;0.05). Among children, BMIz and WHR were greater in the GDM versus NW offspring (P&amp;lt;0.05), with children in the Ob group having a mean BMIz and WHR that was in between NW and GDM. Conclusion: Results support the hypothesis that women with prior GDM exhibit more central adiposity despite having similar BMI as women with Ob without prior GDM. Among children, BMIz and central adiposity increased progressively when comparing offspring of NW, Ob, and GDM mothers. The results indicate that both Ob and GDM in mothers during pregnancy may affect total and central adiposity in children. While additional research is needed, attention to maternal health before and during pregnancy is vital to mitigate against a cardiometabolic disease phenotype in children. Disclosure S. Martin: None. Funding American Heart Association (336101011); University of Alabama at Birmingham (DK079626, DK056336)

Maternal Obesity and Diet Quality Modulate the Villous Placental Metabolome

Abstract Objectives Maternal diet and body composition are important determinants of offspring obesity risk, which may be mediated via changes in placental function. Here we examined the influence of maternal obesity and diet quality on the placental metabolome using untargeted metabolomics. Methods Placenta were collected from a longitudinal observational study in which maternal anthropometrics, body composition, dietary intake (3 d food records) and other variables were collected every trimester. Untargeted metabolomics of villous placental tissues from normal weight (NW, n = 72), overweight (OW, n = 49), and obese women (OB, n = 29) based on BMI at first trimester, were performed using GC-TOF MS. Differential metabolite features were identified using univariate comparisons (ANOVA/Mann Whitney U tests) and partial least squares discriminant analysis (PLS-DA). Results Principal component analysis did not reveal global shifts in the metabolome with maternal OW or OB. While no differences survived multiple testing corrections (P &amp;lt; 0.05), univariate analysis indicated that OW/OB subjects showed increased abundance of 2-deoxypentitol and decreases in maltotriose and 3-hydroxybutanoic acid relative to NW subjects (un-adjusted P &amp;lt; 0.05). Alterations in a number of non-annotated metabolites were also observed between NW, OW and OB groups. PLS-DA models predicted maternal OB status with ∼80% accuracy in held out samples. Predictive metabolites were enriched for aspartate metabolism and ammonia recycling. The global placental metabolome was significantly associated with maternal diet quality (Healthy Eating Index 2010 score averaged over pregnancy; PC1 ANOVA P &amp;lt; 0.01) which was characterized by differences in 138 metabolites (ANOVA, un-adjusted P &amp;lt; 0.05). Abundance of heptadecanoic acid and glycerol-3-galactoside increased with HEI score. Conclusions Maternal obesity appears to alter amino acid or protein metabolism, whereas diet quality seemed to affect metabolism of fatty acids and BCAA. These results suggest a potential shift in nutrient delivery to the offspring. Funding Sources Supported by USDA-ARS Project 6026–51,000-010–05S.

Does Human Milk Insulin Help Program Infant Pancreatic Function? Variation in Neonatal Human Milk Insulin Is Associated with Later Measures of Infant Glycemic Control

Abstract Objectives Whether variation in human milk (HM) insulin contributes to neonatal blood sugar regulation and pancreatic programming remains unknown. This pilot study investigates whether HM insulin concentrations correlate with infant pancreatic function in exclusively breastfed 5-month old infants. We hypothesize that neonatal exposure to elevated HM insulin will “under stimulate” the infant pancreas, resulting in an exaggerated glycemic response to oral glucose at 5 months. Methods Exclusively breastfed infants of normoglycemic mothers (NG; n = 5) and mothers with minor insulin resistance (IR; n = 5) were administered a 1.75 g/kg oral glucose challenge. Infant capillary glucose was assessed at Fasting (&amp;gt;2 hours), 30 minutes (T30) and 60 minute (T60) after glucose administration. Fasting HM insulin was measured at 2-weeks and 5-months. Repeated Measures ANOVA and linear regression analyses were utilized. Results Using repeated measures analysis, the IR group exhibited a more dramatic glycemic response to the glucose challenge (P = 0.031): exhibiting lower fasting glucose (P = 0.085; n = 10) and higher glucose excursion from fasting to T30 (P = 0.007) compared to the NG group. HM insulin did not differ between the NW and IR groups at 2-weeks or 5-months. However, higher HM insulin concentrations at 2-weeks did correlate with a more dramatic infant glycemic response to oral glucose at 5 months. Fasting HM insulin at 2 weeks was positively associated with infant glucose at T30 (P = 0.033) and with the increase in glucose from fasting to T30 (P = 0.081; n = 8). Furthermore, fasting HM insulin at 2-weeks was negatively associated with infant glucose at T60 (P = 0.031) and the change in glucose from T30-T60 (P = 0.032; n = 7). Conclusions These pilot results suggest that HM insulin may contribute to postnatal programming of infant pancreatic function such that chronic exposure to elevated HM insulin may result in a dampened pancreatic response to an oral glucose challenge. Confirmation in a larger sample size is necessary. Funding Sources NIH/NIDDK; The Gerber Foundation.

Activation of Systemic Inflammation and Oxidative Stress in Adolescent Girls with Polycystic Ovary Syndrome in Combination with Metabolic Disorders and Excessive Body Weight.

Relevance: Mitochondrial dysfunction and systemic inflammation are believed to play pivotal role in the pathogenesis of polycystic ovary syndrome (PCOS) and related complications of metabolic disorders in adult patients. Though such researches are limited or almost absent in adolescents. The aim of the study is to evaluate the impact of mitochondrial dysfunction and systemic inflammation on PCOS pathogenesis during adolescence with regard to body mass index and insulin resistance. Design: a case-control study. Methods: The study included 95 adolescent girls (15 to 17 years old inclusive) diagnosed with PCOS based on the Rotterdam criteria. The control group consisted of 30 healthy girls of the same age with a regular menstrual cycle. All participants were subjected to a full clinical and instrumental examination, as well as an assessment of the levels of leptin, C-reactive protein (CRP), and malondialdehyde (MDA) as oxidative stress marker. Serum levels of IL-6, IL-10, IL-18, TNF-α, and plasma concentrations of macrophage migration inhibitory factor (MIF), sFas, and sFasL were determined. Patients with PCOS were divided into groups according to the presence of metabolic disorders (MD) (impaired glucose tolerance and/or over insulin resistance) and normal weight or excessive weight (NW or OW). Results: Patients with PCOS of NW in the absence of metabolic disorders (MD−/NW) had a lower concentration of MDA and a higher level of IL-10 compared to healthy girls (p < 0.05). The group (MD−/NW) was characterized with lower levels of CRP, leptin, MDA, and higher levels of sFasL, when compared to OW patients with PCOS in the absence of metabolic disorders (MD−/OW) (p < 0.05). Overweight adolescent girls with PCOS and metabolic disorders (MD+/OW) showed higher CRP, leptin, and a two-fold increase in IL-6 and IL-18 concentrations compared to the control group of healthy girls (p < 0.05 for all parameters). The group (MD+/OW) was also characterized with higher levels of CRP, leptin, MDA, IL-18, MIF (p < 0.05), when compared to overweight patients with PCOS in the absence of metabolic disorders (MD−/NW). In comparison with the MD−/OW group, the obese insulin resistant girls with PCOS (MD+/OW) had a highera level of IL-18 (p < 0.05). Moreover, the MD+/OW girls demonstrated a significant increase in CRP, MDA and IL-18 levels when compared to the MD+/NW group (p < 0.05). OW girls with PCOS without MD (MD−/OW) had lower concentrations of sFasL compared to healthy girls (p < 0.05), and higher levels of MDA compared to MD+/NW (p < 0.05). Adolescent girls of NW with PCOS and with MD (MD+/NW) had lower levels of MDA compared to the control group of healthy girls (p < 0.05). These data are confirmed by a correlation analysis and two-factor ANOVA test. Conclusions: Lean girls with PCOS demonstrate the protective mechanism of decrease in oxidative stress mediated by the activation of antioxidant defense, reduction of lipid peroxidation and systemic inflammation. Excessive weight and metabolic disorders in adolescents with PCOS are the most significant factors in reducing the capacity of antioxidant systems, activation of oxidative stress, mitochondrial dysfunction, and systemic inflammation.

&lt;p&gt;Increase in Tryptase and Its Role in the Synovial Membrane of Overweight and Obese Patients with Osteoarthritis of the Knee&lt;/p&gt;

PurposeThe mechanisms governing evidence that obesity is a risk factor for osteoarthritis (OA) are not well understood. We previously reported an increase in mast cell (MC) marker expression in the osteoarthritic synovial membrane (SM) of patients with obesity. We hypothesized that an enzyme produced by MC, β-tryptase, may be increased in the SM of obese patients with knee OA and contribute to synovial inflammation. This study investigated the expression of the β-tryptase encoding gene, TPSB2, in the SM of obese patients with knee OA and β-tryptase-mediated regulation of IL-1β in synovial cells.Patients and MethodsA total of 216 patients radiographically diagnosed with knee OA were grouped according to the World Health Organization’s body mass index classifications: normal weight (NW; <25 kg/m2), overweight (OW; 25–29.99 kg/m2) and obese (OB; ≥30 kg/m2). Quantitative polymerase chain reaction was conducted to examine TPSB2 expression in the SM among the three groups. We also examined TPSB2 and IL1B expression in MC-rich (CD3-CD14-CD19-CD90-) and MC-poor (CD3+, CD14+, CD19+, or CD90+) fractions freshly isolated from synovial tissue. Further, the effect of β-tryptase on IL1B expression was investigated in cultured CD14-positive (macrophage-rich fraction) and CD14-negative (fibroblast-rich fraction) cells.ResultsThere was significantly elevated TPSB2 expression in the OW and OB groups compared to the NW group. The MC-rich fraction had significantly higher levels of TPSB2, CD117 and CD203c than the MC-poor fraction. Recombinant human β-tryptase stimulated IL1B expression in both the synovial fibroblast and macrophage fractions.ConclusionObese patients with knee OA showed elevated TPSB2 expression in the SM. Tryptase may play a role in synovial inflammation in obese patients with OA.

Weight and LVAD Outcomes; Not Just a "Bridge to the Fridge?"

Obesity in LVAD recipients has been well documented. There is a lack of data on the predictive effect of baseline weight and weight gain after LVAD implantation on morbidity and mortality. The aim of our study was to evaluate if weight at LVAD implant and the change in weight during LVAD support could predict morbidity and/or mortality. We reviewed the impact of baseline weight and weight gain on post-LVAD survival in patients who received a durable LVAD at our institution from January 1, 2014 until December 31, 2017. Patients who were supported for more than 12 months were divided into two groups: patients with baseline BMI < 30 (NW) and BMI > 30 (OW) and were evaluated for association of weight change with overall survival and freedom from LVAD related complications. Baseline characteristics of 189 patients are summarized in Table 1. One year survival was 74 ± 5% in patients with baseline BMI <30, and 77 ± 5% in patients with BMI >30. Baseline BMI was not associated with survival in multivariate Cox proportional hazard analysis (P = 0.91). Out of 89 patients who were still being supported 12 months after the LVAD implantation, 51 (57%) had BMI >30. Median weight gain in NW group at 12 months was 12(6,18)kg compared to 7(3,12)kg in OW group (P=0.02). There was no association of BMI at 12 months or weight change with overall post-LVAD survival, freedom from infection, pump malfunction, and neurological dysfunction. Freedom from right heart dysfunction at 12 months was 84 ± 5% in patients with BMI>30 compared to 97±3% in patients with BMI<30. For patients who crossed over from a baseline BMI<30 to BMI>30 at 12 months, weight gain emerged as a significant predictor of right heart failure (HR: 16.133 [95% CI; 1.806-145.026] p=0.013) CONCLUSION: Baseline, as well as 12 months post implantation BMI, had no impact on overall post-LVAD survival. Patients with NW at implant who crossed over to OW had no effect on survival, infection, pump complication or neurological dysfunction. However, this population had significantly less freedom from right heart failure.