Developmental Milestone Attainment in US Children Before and During the COVID-19 Pandemic.

Importance: Restrictions related to the COVID-19 pandemic disrupted the lives of young children, but the association between the pandemic and any changes in early childhood developmental milestone achievement in the US remains unclear. Objectives: To determine the association between the COVID-19 pandemic and changes in developmental screening scores among US children aged 0 to 5 years and to investigate whether caregivers self-reported more worries about their children or concerns about children's behavior during the pandemic, regardless of milestone achievement. Design, Setting, and Participants: This was a cohort study using an interrupted time series analysis comparing prepandemic (March 1, 2018, to February 29, 2020), interruption (March 1 to May 31, 2020), and intrapandemic (June 1, 2020, to May 30, 2022) periods among 50 205 children (randomly sampled from a population of 502 052 children) aged 0 to 5 years whose parents or caregivers completed developmental screening at pediatric visits at US pediatric primary care practices participating in a web-based clinical process support system. Exposure: COVID-19 pandemic period. Main Outcomes and Measures: Age-standardized Ages and Stages Questionnaire, Third Edition (ASQ) domain scores (communication, personal-social, problem-solving, gross motor, fine motor), and rate of caregivers' concerns about the child's behavior or worries about the child as measured on the ASQ. Results: A total of 50 205 children (25 852 [51.5%] male; mean [SD] age, 18.6 [16.0] months) and 134 342 ASQ observations were included. In adjusted models, significant age-specific mean score decreases from prepandemic to intrapandemic were observed in communication (-0.029; 95% CI, -0.041 to -0.017), problem-solving (-0.018; 95% CI, -0.030 to -0.006), and personal-social (-0.016; 95% CI, -0.028 to -0.004) domains. There were no changes in fine or gross motor domains prepandemic to intrapandemic. For infants aged 0 to 12 months, similar effect sizes were observed but only for communication (-0.027; 95% CI, -0.044 to -0.011) and problem-solving (-0.018; 95% CI, -0.035 to -0.001). After accounting for age-standardized ASQ scores, caregiver worries about the child increased slightly in the intrapandemic period compared with the prepandemic period (rate ratio, 1.088; 95% CI, 1.036-1.143), but there were no changes in caregiver concerns about the child's behavior. While changes in developmental screening scores were modest (2%-3%), nationwide, this could translate to more than 1500 additional recommended developmental referrals over baseline each month. Conclusions and Relevance: Modest changes in developmental screening scores are reassuring in the short term but may tax an already overburdened developmental behavioral pediatrics infrastructure. Continued attention to developmental surveillance is critical since the long-term population- and individual-level implications of these changes are unclear.

"It Can Be Confusing": Family Perspectives on Food Insecurity Screening in Urban Pediatric Primary Care Clinics.

Food insecurity, for which families are routinely screened at medical visits, has deleterious health consequences. This study sought to understand the lived experiences of families with lower incomes participating in food insecurity screening at two urban pediatric primary care clinics. Forty-three semi-structured interviews were performed in English and Spanish with families with public insurance after well visits where food insecurity screening was documented. Immersion-crystallization analysis was used to identify salient themes. Families reported discomfort with food insecurity screening, but nonetheless found screening acceptable when performed universally and privately. Families shared confusion about how their screening responses would be used and expected that resources would be available promptly for those who screen positive. Food insecurity screening may be improved for families through explanations of how responses will be used, allowing families to opt out, soliciting family preferences for resource referral, and offering promptly available resources for families with food insecurity.

"Why Do They Want to Know?": A Qualitative Assessment of Caregiver Perspectives on Social Drivers of Health Screening in Pediatric Primary Care.

OBJECTIVE: Despite strong evidence that social factors have a large influence on child health, systematic screening for social needs is not performed universally in pediatric primary care. This is due to multiple barriers, including concerns about acceptability to families. This study sought to assess family acceptability of social needs screening in pediatric primary care. METHODS: Eight semi-structured focus groups were performed with English and Spanish-speaking caregivers of pediatric patients from a diverse academic medical center. Focus groups explored the acceptability of social domains including housing, education, finances, food access, and safety. Focus group transcripts were qualitatively analyzed to identify themes. RESULTS: Four salient themes emerged: 1) the acceptability of social determinants of health screening questions was tied to participants' understanding of the connection between the topic and child health, 2) families preferred a warm handoff to community services, 3) families feared child protective services intervention as a result of sharing unmet social needs, and 4) positive provider rapport was an important factor in choosing to share social needs. CONCLUSIONS: Pediatric primary care providers should feel comfortable implementing social needs screening when they can clearly explain the connection to child health. They should become knowledgeable about organizations and partners within their communities and feel empowered to connect patients to these resources.

Treatment of anger problems in previously deployed post-911 veterans: A randomized controlled trial.

BACKGROUND: Problems with anger and aggression affect many veterans who have deployed to a warzone, resulting in serious impairment in multiple aspects of functioning. Controlled studies are needed to improve treatment options for these veterans. This randomized controlled trial compared an individually delivered cognitive behavioral therapy adapted from Novaco's Anger Control Therapy to a manualized supportive therapy to control for common therapeutic factors. METHODS: Ninety-two post-911 veterans deployed during Operation Enduring Freedom (OEF), Operation Iraqi Freedom (OIF), or Operation New Dawn (OND) with moderate to severe anger problems were randomized to receive the cognitive behavioral intervention (CBI) or the supportive intervention (SI). Anger, aggression, multiple areas of functioning and quality of life were assessed at multiple time points inclu\ding 3- and 6-month follow-up. RESULTS: Hierarchical linear modeling (HLM) analyses showed significant treatment effects favoring CBI for anger severity, social and interpersonal functioning, and quality of life. The presence of a PTSD diagnosis did not affect outcomes. CONCLUSIONS: CBI is an effective treatment for OEF/OIF/OND veterans with anger problems following deployment, regardless of PTSD diagnosis.

Waiting times in emergency departments: exploring the factors associated with longer patient waits for emergency care in England using routinely collected daily data.

BACKGROUND: Long lengths of stay (also called waiting times) in emergency departments (EDs) are associated with higher patient mortality and worse outcomes. OBJECTIVE: To add to the literature using high-frequency data from a large number of hospitals to analyse factors associated with long waiting times, including exploring non-linearities for 'tipping points'. METHODS: Multivariate ordinary least squares regressions with fixed effects were used to analyse factors associated with the proportion of patients in EDs in England waiting more than 4 hours to be seen, treated and admitted or discharged. Daily situation reports (Sitrep), hospital episode statistics and electronic staffing records data over 90 days between December 2016 and February 2017 were used for all 138 English NHS healthcare providers with a major ED. RESULTS: Higher inpatient bed occupancy was correlated with longer ED waiting times, with a non-linear association. In a full hospital, with 100% bed occupancy, the proportion of patients who remained in the ED for more than 4 hours was 9 percentage points higher (95% CI 7.5% to 11.1%) than with an 85% occupancy level. For each percentage point change in the following factors, the proportion of ED stays over 4 hours also increased: more inpatients with hospital length of stay over 21 days (0.07%, 95% CI 0.008% to 0.13%); higher emergency admissions (0.08%, 95% CI 0.06% to 0.10%); and lower discharges relative to admissions on the same day (0.04%, 95% CI 0.02% to 0.06%), the following day (0.05%, 95% CI 0.03% to 0.06%) and at 2 days (0.05%, 95% CI 0.04% to 0.07%). CONCLUSIONS: These results suggest that tackling patient flow and capacity in the wider hospital, particularly very high bed occupancy levels and patient discharge, is important to reduce ED waiting times and improve patient outcomes.

Concordance of Vancomycin Population-Predicted Pharmacokinetics with Patient-Specific Pharmacokinetics in Adult Hospitalized Patients: A Case Series.

BACKGROUND: Vancomycin empiric therapy is commonly dosed using clinical algorithms adapted from population-predicted pharmacokinetic parameters. However, precise dosing of vancomycin can be designed using patient-specific pharmacokinetic calculations. OBJECTIVE: The objective of this study is to assess the correlational fit between vancomycin population-predicted and patient-specific pharmacokinetic parameters [elimination rate constant (Ke) and half-life (t1/2)] in a case series of adult hospitalized patients. METHODS: This is a single-center case series of hospitalized adult patients who received vancomycin, had creatinine clearance calculation for derivation of population-predicted pharmacokinetic parameters, and had two vancomycin concentrations for calculation of patient-specific pharmacokinetic parameters. The primary objective of this case series is to evaluate the correlation between population-predicted and patient-specific pharmacokinetic parameters. The secondary objectives of this study are to evaluate the mean bias and precision between the population-predicted and patient-specific pharmacokinetic parameters and to assess the correlation between population-predicted and patient-specific pharmacokinetic parameters in special population subgroups (obese patients with body mass index ≥ 30 kg/m2 and patients with renal dysfunction). All correlation analyses were performed on the population-predicted pharmacokinetics using diverse methods of estimating renal function (Salazar-Corcoran and Cockcroft-Gault methods using either ideal, actual, or adjusted body weights). All significance testing was set at an α of < 0.05. IBM SPSS Statistics version 25 and SAS version 9.4 were used to conduct all statistical analyses. RESULTS: A total of 30 patients were included in the study; 33.3% (10/30) of the patients were obese and 56.7% (17/30) had renal dysfunction. In all patients in the study, the calculated population-predicted Ke and t1/2 using all four creatinine clearance estimation methods were each significantly correlated with patient-specific Ke and t1/2 (all Pearson correlation coefficients [r]: > + 0.7, p < 0.001). The population-predicted Ke and t1/2 calculated using Cockcroft-Gault creatinine clearance using adjusted body weight showed the strongest association with patient-specific Ke and t1/2. In the subgroup analyses, all the population-predicted Ke and t1/2 using four creatinine clearance estimation methods were each significantly correlated with patient-specific Ke and t1/2. The exception was the population-predicted t1/2 derived from Cockcroft-Gault creatinine clearance using actual body weight that did not show a significant correlation with patient-specific t1/2 in obese patients. CONCLUSIONS: In this case series, population-predicted pharmacokinetic parameters were strongly correlated with patient-specific pharmacokinetic parameters. The vancomycin population-predicted pharmacokinetic formula can be used safely to predict a patient's vancomycin pharmacokinetic disposition and can be maintained as an empiric dosing strategy in various hospitalized adult patients.

Visual and oculomotor outcomes in children with prenatal opioid exposure.

PURPOSE OF REVIEW: To summarize the visual and oculomotor outcomes in children with prenatal opioid exposure and review the effects of opioids on the developing central nervous system. RECENT FINDINGS: Animal models and imaging studies in children suggest that prenatal opioid exposure may affect neuronal survival and result in delayed maturation of white matter tracts and decreased volumes in certain brain areas. Visual evoked potential testing in children demonstrates delayed maturation of the afferent visual system in opioid-exposed groups compared with controls, though 'catch-up' development is seen with longitudinal follow-up. Strabismus and nystagmus are also more common in exposed children, and these findings appear to persist. SUMMARY: As rates of opioid dependence and prenatal opioid exposure continue to increase, it is important to evaluate the short-term and long-term effects of opioids on the developing visual system. An understanding of these risks is important when counseling the parents or guardians of opioid-exposed children, though larger studies with more long-term follow-up will improve our prognostic abilities.

Don't Miss This! Red Flags in the Pediatric Eye Exam: Pupils.

The pupillary exam in the pediatric population is a vital part of any clinician's workup. In the right clinical setting, pupillary abnormalities such as anisocoria, light-near dissociation, an afferent pupillary defect, and paradoxic pupillary constriction in the dark can be red flags that trigger further examination and workup. Through both careful physical examination and detailed history-taking and observation, potentially vision- and life-threatening conditions can be detected.

Impact of dietary fiber supplementation on modulating microbiota-host-metabolic axes in obesity.

Low dietary fiber intake is associated with higher rates of microbiota-associated chronic diseases such as obesity. Low-fiber diets alter not only microbial composition but also the availability of metabolic end products derived from fermentation of fiber. Our objective was to examine the effects of dietary fiber supplementation on gut microbiota and associated fecal and serum metabolites in relation to metabolic markers of obesity. We conducted a 12-week, single-center, double-blind, placebo-controlled trial with 53 adults with overweight or obesity. They were randomly assigned to a pea fiber (PF, 15 g/d in wafer form; n=29) or control (CO, isocaloric amount of wafers; n=24) group. Blood and fecal samples were collected at baseline and 12 weeks. Serum metabolomics, gut microbiota and fecal short-chain fatty acids (SCFAs) and bile acids (BAs) were examined. Within-group but not between-group analysis showed a significant effect of treatment on serum metabolites at 12 weeks compared to baseline. Fiber significantly altered fecal SCFAs and BAs with higher acetate and reduced isovalerate, cholate, deoxycholate and total BAs content in the PF group compared to baseline. Microbiota was differentially modulated in the two groups, including an increase in the SCFA producer Lachnospira in the PF group and decrease in the CO group. The change in body weight of participants showed a negative correlation with their change in Lachnospira (r=-0.463, P=.006) abundance. The current study provides insight into the actions of pea fiber and its impact on modulating microbiota-host-metabolic axes in obesity.

Treatment of trauma related anger in operation enduring freedom, operation Iraqi freedom, and operation New Dawn veterans: Rationale and study protocol.

BACKGROUND: Problems with anger and aggression are highly prevalent in Veterans of multiple war eras, including the most recent conflicts in Afghanistan (Operation Enduring Freedom; OEF) and Iraq (Operation Iraqi Freedom; OIF). The consequences of these problems, such as increased rates of divorce, domestic violence, occupational instability, arrests and incarceration, are often devastating. Despite the seriousness of these problems, relatively little is known about effective treatments for anger in Veterans. METHOD AND DESIGN: This paper describes the rationale and study protocol of a randomized controlled trial comparing an adapted cognitive behavioral intervention (CBI) with an active control condition (supportive intervention, SI) for the treatment of anger problems in OEF/OIF Veterans. The sample includes 92 OEF/OIF Veterans, randomized to CBI or SI. Both treatments include 12 weekly, 75-min individual sessions. Participants are assessed at baseline, after sessions 4 and 8, at post-treatment, and at 3 and 6 months post-treatment. Primary outcomes are reduction in anger and aggression; secondary outcomes are improved functioning and quality of life. We hypothesize that CBI will be associated with significantly more improvement than SI on primary and secondary measures. DISCUSSION: Findings from this study will help to address the gap in evidence for effective treatments for anger in Veterans. The use of an active control condition will provide a stringent test of the effects of CBI beyond that of common factors of psychotherapy such as therapeutic relationship, mobilization of hope, and support. Findings have the potential to improve treatment outcomes for Veterans struggling with post-deployment anger problems.

Consuming yellow pea fiber reduces voluntary energy intake and body fat in overweight/obese adults in a 12-week randomized controlled trial.

BACKGROUND & AIMS: The purpose of this randomized, double-blind, placebo-controlled study was to assess the effects of yellow pea fiber intake on body composition and metabolic markers in overweight/obese adults. METHODS: Participants (9 M/41 F; age 44 ± 15 y, BMI 32.9 ± 5.9 kg/m2) received isocaloric doses of placebo (PL) or pea fiber (PF; 15 g/d) wafers for 12 weeks. Outcome measures included changes in anthropometrics, body composition (DXA), oral glucose tolerance test (OGTT), food intake (ad libitum lunch buffet), and biochemical indices. RESULTS: The PF group lost 0.87 ± 0.37 kg of body weight, primarily due to body fat (-0.74 ± 0.26 kg), whereas PL subjects gained 0.40 ± 0.39 kg of weight over the 12 weeks (P = 0.022). The PF group consumed 16% less energy at the follow-up lunch buffet (P = 0.026), whereas the PL group did not change. During the OGTT, glucose area under the curve (AUC) was lower in PF subjects at follow-up (P = 0.029); insulin increased in both groups over time (P = 0.008), but more so in the PL group (38% higher AUC vs. 10% higher in the PF group). There were no differences in gut microbiota between groups. CONCLUSIONS: In the absence of other lifestyle changes, incorporating 15 g/day yellow pea fiber may yield small but significant metabolic benefits and aid in obesity management. Clinical Trial Registry: ClinicalTrials.gov NCT01719900.

An LC-MRM method for measuring intestinal triglyceride assembly using an oral stable isotope-labeled fat challenge.

AIM: A traditional oral fatty acid challenge assesses absorption of triacylglycerol (TG) into the periphery through the intestines, but cannot distinguish the composition or source of fatty acid in the TG. Stable isotope-labeled tracers combined with LC-MRM can be used to identify and distinguish TG synthesized with dietary and stored fatty acids. RESULTS: Concentrations of three abundant TGs (52:2, 54:3 and 54:4) were monitored for incorporation of one or two (2)H11-oleate molecules per TG. This method was subjected to routine assay validation and meets typical requirements for an assay to be used to support clinical studies. CONCLUSION: Calculations for the fractional appearance rate of TG in plasma are presented along with the intracellular enterocyte precursor pool for 12 study participants.

Gut microbiota manipulation with prebiotics in patients with non-alcoholic fatty liver disease: a randomized controlled trial protocol.

BACKGROUND: Evidence for the role of the gut microbiome in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) is emerging. Strategies to manipulate the gut microbiota towards a healthier community structure are actively being investigated. Based on their ability to favorably modulate the gut microbiota, prebiotics may provide an inexpensive yet effective dietary treatment for NAFLD. Additionally, prebiotics have established benefits for glucose control and potentially weight control, both advantageous in managing fatty liver disease. Our objective is to evaluate the effects of prebiotic supplementation, adjunct to those achieved with diet-induced weight loss, on heptic injury and liver fat, the gut microbiota, inflammation, glucose tolerance, and satiety in patients with NAFLD. METHODS/DESIGN: In a double blind, placebo controlled, parallel group study, adults (BMI ≥25) with confirmed NAFLD will be randomized to either a 16 g/d prebiotic supplemented group or isocaloric placebo group for 24 weeks (n = 30/group). All participants will receive individualized dietary counseling sessions with a registered dietitian to achieve 10 % weight loss. Primary outcome measures include change in hepatic injury (fibrosis and inflammation) and liver fat. Secondary outcomes include change in body composition, appetite and dietary adherence, glycemic and insulinemic responses and inflammatory cytokines. Mechanisms related to prebiotic-induced changes in gut microbiota (shot-gun sequencing) and their metabolic by-products (volatile organic compounds) and de novo lipogenesis (using deuterium incorporation) will also be investigated. DISCUSSION: There are currently no medications or surgical procedures approved for the treatment of NAFLD and weight loss via lifestyle modification remains the cornerstone of current care recommendations. Given that prebiotics target multiple metabolic impairments associated with NAFLD, investigating their ability to modulate the gut microbiota and hepatic health in patients with NAFLD is warranted. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02568605) Registered 30 September 2015.

Mitochondrial metabolism mediates oxidative stress and inflammation in fatty liver.

Mitochondria are critical for respiration in all tissues; however, in liver, these organelles also accommodate high-capacity anaplerotic/cataplerotic pathways that are essential to gluconeogenesis and other biosynthetic activities. During nonalcoholic fatty liver disease (NAFLD), mitochondria also produce ROS that damage hepatocytes, trigger inflammation, and contribute to insulin resistance. Here, we provide several lines of evidence indicating that induction of biosynthesis through hepatic anaplerotic/cataplerotic pathways is energetically backed by elevated oxidative metabolism and hence contributes to oxidative stress and inflammation during NAFLD. First, in murine livers, elevation of fatty acid delivery not only induced oxidative metabolism, but also amplified anaplerosis/cataplerosis and caused a proportional rise in oxidative stress and inflammation. Second, loss of anaplerosis/cataplerosis via genetic knockdown of phosphoenolpyruvate carboxykinase 1 (Pck1) prevented fatty acid-induced rise in oxidative flux, oxidative stress, and inflammation. Flux appeared to be regulated by redox state, energy charge, and metabolite concentration, which may also amplify antioxidant pathways. Third, preventing elevated oxidative metabolism with metformin also normalized hepatic anaplerosis/cataplerosis and reduced markers of inflammation. Finally, independent histological grades in human NAFLD biopsies were proportional to oxidative flux. Thus, hepatic oxidative stress and inflammation are associated with elevated oxidative metabolism during an obesogenic diet, and this link may be provoked by increased work through anabolic pathways.

Exercise training modifies gut microbiota in normal and diabetic mice.

Cecal microbiota from type 2 diabetic (db/db) and control (db/(+)) mice was obtained following 6 weeks of sedentary or exercise activity. qPCR analysis revealed a main effect of exercise, with greater abundance of select Firmicutes species and lower Bacteroides/Prevotella spp. in both normal and diabetic exercised mice compared with sedentary counterparts. Conversely, Bifidobacterium spp. was greater in exercised normal but not diabetic mice (exercise × diabetes interaction). How exercise influences gut microbiota requires further investigation.

Palmitoleic acid is elevated in fatty liver disease and reflects hepatic lipogenesis.

BACKGROUND: Biochemical evidence has linked the coordinate control of fatty acid (FA) synthesis with the activity of stearoyl-CoA desaturase-1 (SCD1). The ratio of 16:1n-7 to 16:0 [SCD116] in plasma triacylglycerol FA has been used as an index to reflect liver SCD116 activity and has been proposed as a biomarker of FA synthesis, although this use has not been validated by comparison with isotopically measured de novo lipogenesis (DNL(Meas)). OBJECTIVE: We investigated plasma lipid 16:1n-7 and FA indexes of elongation and desaturation in relation to lipogenesis. DESIGN: In this cross-sectional investigation of metabolism, 24 overweight adults, who were likely to have elevated DNL, consumed D2O for 10 d and had liver fat (LF) measured by magnetic resonance spectroscopy. Very-low-density lipoprotein (VLDL)-triacylglycerols and plasma free FA [nonesterified fatty acids (NEFAs)] were analyzed by using gas chromatography for the FA composition (molar percentage) and gas chromatography-mass spectrometry and gas chromatography-combustion isotope ratio mass spectrometry for deuterium enrichment. RESULTS: In all subjects, VLDL-triacylglycerol 16:1n-7 was significantly (P < 0.01) related to DNL(Meas) (r = 0.56), liver fat (r = 0.53), and adipose insulin resistance (r = 0.56); similar positive relations were shown with the SCD116 index, and the pattern in NEFAs echoed that of VLDL-triacylglycerols. Compared with subjects with low LF (3.1 ± 2.7%; n = 11), subjects with high LF (18.4 ± 3.6%; n = 13) exhibited a 45% higher VLDL-triacylglycerol 16:1n-7 molar percentage (P < 0.01), 16% of subjects had lower 18:2n-6 (P = 0.01), and 27% of subjects had higher DNL as assessed by using a published DNL index (ratio of 16:0 to 18:2n-6; P = 0.03), which was isotopically confirmed by DNL(Meas) (increased 2.5-fold; P < 0.01). Compared with 16:0 in the diet, the low amount of dietary 16:1n-7 in VLDL-triacylglycerols corresponded to a stronger signal of elevated DNL. CONCLUSION: The current data provide support for the use of the VLDL-triacylglycerol 16:1n-7 molar percentage as a biomarker for elevated liver fat when isotope use is not feasible; however, larger-scale confirmatory studies are needed.

Evaluation of yellow pea fibre supplementation on weight loss and the gut microbiota: a randomized controlled trial.

BACKGROUND: Fibre intake among North Americans is currently less than half the recommended amount. Consumers are interested in food products that could promote weight loss and improve health. Consequently, evaluation of unique fibre sources with potential gut-mediated benefits for metabolic health warrants investigation. Our objective is to assess the effects of yellow pea fibre supplementation on weight loss and gut microbiota in an overweight and obese adult population. METHODS/DESIGN: In a double blind, placebo controlled, parallel group study, overweight and obese (BMI = 25-38) adults will be randomized to either a 15 g/d yellow pea fibre supplemented group or isocaloric placebo group for 12 weeks (n = 30/group). The primary outcome measure is a change in body fat from baseline to 12 weeks. Secondary outcomes include glucose tolerance, appetite regulation, serum lipids and inflammatory markers. Anthropometric data (height, weight, BMI, and waist circumference) and food intake (by 3-day weighed food records) will be measured at baseline and every 4 weeks thereafter. Subjective ratings of appetite will be recorded by participants at home on a weekly basis using validated visual analogue scales. At week 0 and at the end of the study (week 12), an ad libitum lunch buffet protocol for objective food intake measures and dual-energy X-ray absorptiometry (DXA) scan for body composition will be completed. Participants will be instructed not to change their exercise habits during the 12 week study. Glucose and insulin will be measured during an oral glucose tolerance test at weeks 0 and 12. Levels of lipids and CRP will be measured and inflammatory markers (adiponectin, leptin, TNF-α, IL-6 and IL-8) in the serum will be quantified using Milliplex kits. Mechanisms related to changes in gut microbiota, serum and fecal water metabolomics will be assessed. DISCUSSION: Globally the development of functional foods and functional food ingredients are critically needed to curb the rise in metabolic disease. This project will assess the potential of yellow pea fibre to improve weight control via gut-mediated changes in metabolic health in overweight and obese adults. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01719900) Registered October 23, 2012.

Increased de novo lipogenesis is a distinct characteristic of individuals with nonalcoholic fatty liver disease.

BACKGROUND & AIMS: There have been few studies of the role of de novo lipogenesis in the development of nonalcoholic fatty liver disease (NAFLD). We used isotope analyses to compare de novo lipogenesis and fatty acid flux between subjects with NAFLD and those without, matched for metabolic factors (controls). METHODS: We studied subjects with metabolic syndrome and/or levels of alanine aminotransferase and aspartate aminotransferase >30 mU/L, using magnetic resonance spectroscopy to identify those with high levels (HighLF, n = 13) or low levels (LowLF, n = 11) of liver fat. Clinical and demographic information was collected from all participants, and insulin sensitivity was measured using the insulin-modified intravenous glucose tolerance test. Stable isotopes were administered and gas chromatography with mass spectrometry was used to analyze free (nonesterified) fatty acid (FFA) and triacylglycerol flux and lipogenesis. RESULTS: Subjects with HighLF (18.4% ± 3.6%) had higher plasma levels of FFAs during the nighttime and higher concentrations of insulin than subjects with LowLF (3.1% ± 2.7%; P = .04 and P < .001, respectively). No differences were observed between groups in adipose flux of FFAs (414 ± 195 µmol/min for HighLF vs 358 ± 105 µmol/min for LowLF; P = .41) or production of very-low-density lipoprotein triacylglycerol from FFAs (4.06 ± 2.57 µmol/min vs 4.34 ± 1.82 µmol/min; P = .77). In contrast, subjects with HighLF had more than 3-fold higher rates of de novo fatty acid synthesis than subjects with LowLF (2.57 ± 1.53 µmol/min vs 0.78 ± 0.42 µmol/min; P = .001). As a percentage of triacylglycerol palmitate, de novo lipogenesis was 2-fold higher in subjects with HighLF (23.2% ± 7.9% vs 10.1% ± 6.7%; P < .001); this level was independently associated with the level of intrahepatic triacylglycerol (r = 0.53; P = .007). CONCLUSIONS: By administering isotopes to subjects with NAFLD and control subjects, we confirmed that those with NAFLD have increased synthesis of fatty acids. Subjects with NAFLD also had higher nocturnal plasma levels of FFAs and did not suppress the contribution from de novo lipogenesis on fasting. These findings indicate that lipogenesis might be a therapeutic target for NAFLD.

De novo lipogenesis and cholesterol synthesis in humans with long-standing type 1 diabetes are comparable to non-diabetic individuals.

BACKGROUND: Synthesis of lipid species, including fatty acids (FA) and cholesterol, can contribute to pathological disease. The purpose of this study was to investigate FA and cholesterol synthesis in individuals with type 1 diabetes, a group at elevated risk for vascular disease, using stable isotope analysis. METHODS: Individuals with type 1 diabetes (n = 9) and age-, sex-, and BMI-matched non-diabetic subjects (n = 9) were recruited. On testing day, meals were provided to standardize food intake and elicit typical feeding responses. Blood samples were analyzed at fasting (0 and 24 h) and postprandial (2, 4, 6, and 8 hours after breakfast) time points. FA was isolated from VLDL to estimate hepatic FA synthesis, whereas free cholesterol (FC) and cholesteryl ester (CE) was isolated from plasma and VLDL to estimate whole-body and hepatic cholesterol synthesis, respectively. Lipid synthesis was measured using deuterium incorporation and isotope ratio mass spectrometry. RESULTS: Fasting total hepatic lipogenesis (3.91 ± 0.90% vs. 5.30 ± 1.22%; P = 0.41) was not significantly different between diabetic and control groups, respectively, nor was synthesis of myristic (28.60 ± 4.90% vs. 26.66 ± 4.57%; P = 0.76), palmitic (12.52 ± 2.75% vs. 13.71 ± 2.64%; P = 0.65), palmitoleic (3.86 ± 0.91% vs. 4.80 ± 1.22%; P = 0.65), stearic (5.55 ± 1.04% vs. 6.96 ± 0.97%; P = 0.29), and oleic acid (1.45 ± 0.28% vs. 2.10 ± 0.51%; P = 0.21). Postprandial lipogenesis was also not different between groups (P = 0.38). Similarly, fasting synthesis of whole-body FC (8.2 ± 1.3% vs. 7.3 ± 0.8%/day; P = 0.88) and CE (1.9 ± 0.4% vs. 2.0 ± 0.3%/day; P = 0.96) and hepatic FC (8.2 ± 2.0% vs. 8.1 ± 0.8%/day; P = 0.72) was not significantly different between diabetic and control subjects. CONCLUSIONS: Despite long-standing disease, lipogenesis and cholesterol synthesis was not different in individuals with type 1 diabetes compared to healthy non-diabetic humans.