A randomized feasibility trial of medium chain triglyceride-supplemented ketogenic diet in people with Parkinson's disease.

BACKGROUND: A ketogenic diet (KD) may benefit people with neurodegenerative disorders marked by mitochondrial depolarization/insufficiency, including Parkinson's disease (PD). OBJECTIVE: Evaluate whether a KD supplemented by medium chain triglyceride (MCT-KD) oil is feasible and acceptable for PD patients. Furthermore, we explored the effects of MCT-KD on blood ketone levels, metabolic parameters, levodopa absorption, mobility, nonmotor symptoms, simple motor and cognitive tests, autonomic function, and resting-state electroencephalography (rsEEG). METHODS: A one-week in-hospital, double-blind, randomized, placebo-controlled diet (MCT-KD vs. standard diet (SD)), followed by an at-home two-week open-label extension. The primary outcome was KD feasibility and acceptability. The secondary outcome was the change in Timed Up & Go (TUG) on day 7 of the diet intervention. Additional exploratory outcomes included the N-Back task, Unified Parkinson's Disease Rating Scale, Non-Motor Symptom Scale, and rsEEG connectivity. RESULTS: A total of 15/16 subjects completed the study. The mean acceptability was 2.3/3, indicating willingness to continue the KD. Day 7 TUG time was not significantly different between the SD and KD groups. The nonmotor symptom severity score was reduced at the week 3 visit and to a greater extent in the KD group. UPDRS, 3-back, and rsEEG measures were not significantly different between groups. Blood ketosis was attained by day 4 in the KD group and to a greater extent at week 3 than in the SD group. The plasma levodopa metabolites DOPAC and dopamine both showed nonsignificant increasing trends over 3 days in the KD vs. SD groups. CONCLUSIONS: An MCT-supplemented KD is feasible and acceptable to PD patients but requires further study to understand its effects on symptoms and disease. TRIAL REGISTRATION: Trial Registration Number NCT04584346, registration dates were Oct 14, 2020 - Sept 13, 2022.

Lower subjective social status is associated with increased adiposity and self-reported eating in the absence of hunger due to negative affect among children reporting teasing distress.

OBJECTIVES: Low social standing and teasing are independently associated with increased body mass index (BMI) and overeating in children. However, children with low social status may be vulnerable to teasing. METHODS: We tested the statistical interaction of subjective social status (SSS) and subjective socioeconomic status (SSES) and teasing distress on BMI, fat mass index (FMI), and eating in the absence of hunger (EAH) in children (Mage = 13.09 years, SD = 2.50 years; 27.8% overweight/obese). Multiple linear regressions identified the main effects of self-reported SSS (compared to peers in school), distress due to teasing, and their interaction on BMI (n = 115), FMI (n = 114), and child- (n = 100) and parent-reported (n = 97) EAH. RESULTS: Teasing distress was associated with greater BMI, FMI, and child-reported EAH due to negative affect (a subscale of EAH) and total EAH scores. There were no associations of SSS with these outcomes. However, there was an interaction between SSS and teasing distress for BMI, FMI, and EAH from negative affect such that lower SSS was associated with higher BMI, FMI, and EAH from negative affect in the presence of teasing distress. However, there were no main effects or interactions (with teasing distress) of SSES on the outcomes. CONCLUSIONS: These findings suggest that the relationship between lower SSS and increased adiposity and overeating behaviors may be exacerbated by other threats to social standing, such as teasing. Children exposed to multiple social threats may be more susceptible to eating beyond physiological need and obesity than those who experience a single form of perceived social disadvantage.

Youth's energy intake during a laboratory-based loss-of-control eating paradigm: Associations with reported current dieting.

Dieting is theorized as a risk factor for loss-of-control (LOC)-eating (i.e., feeling a sense of lack of control while eating). Support for this association has largely relied on retrospective self-report data, which does not always correlate with objectively assessed eating behavior in youth. We hypothesized that during a laboratory-based LOC-eating paradigm, children and adolescents who reported current (at the time of the visit) dieting would consume meals consistent with LOC-eating (greater caloric intake, and intake of carbohydrates and fats, but less intake of protein). Participants were presented with a buffet-style meal and instructed to "Let yourself go and eat as much as you want." Current dieting (i.e., any deliberate change to the amount or type of food eaten to influence shape or weight, regardless of how effective the changes are) was assessed via interview. General linear models were adjusted for fat mass (%), lean mass (kg), height, sex, protocol, race and ethnicity, pre-meal hunger and minutes since consumption of a breakfast shake. Of 337 participants (Mage 12.8 ± 2.7y; 62.3 % female; 45.7 % non- Hispanic White and 26.1 % non-Hispanic Black; MBMIz 0.78 ± 1.11), only 33 (9.8 %) reported current dieting. Current dieting was not significantly associated with total energy intake (F = 1.63, p = .20, ηp2 = 0.005), or intake from carbohydrates (F = 2.45, p = .12, ηp2 = 0.007), fat (F = 2.65, p = .10, ηp2 = 0.008), or protein (F = 0.39, p = .53, ηp2 = 0.001). Contrary to theories that dieting promotes LOC-eating, current dieting was not associated with youth's eating behavior in a laboratory setting. Experimental approaches for investigating dieting are needed to test theories that implicate dieting in pediatric LOC-eating.

Beyond day and night: The importance of ultradian rhythms in mouse physiology.

Our circadian world shapes much of metabolic physiology. In mice ∼40% of the light and ∼80% of the dark phase time is characterized by bouts of increased energy expenditure (EE). These ultradian bouts have a higher body temperature (Tb) and thermal conductance and contain virtually all of the physical activity and awake time. Bout status is a better classifier of mouse physiology than photoperiod, with ultradian bouts superimposed on top of the circadian light/dark cycle. We suggest that the primary driver of ultradian bouts is a brain-initiated transition to a higher defended Tb of the active/awake state. Increased energy expenditure from brown adipose tissue, physical activity, and cardiac work combine to raise Tb from the lower defended Tb of the resting/sleeping state. Thus, unlike humans, much of mouse metabolic physiology is episodic with large ultradian increases in EE and Tb that correlate with the active/awake state and are poorly aligned with circadian cycling.

Diabetes Technology Meeting 2023.

Diabetes Technology Society hosted its annual Diabetes Technology Meeting from November 1 to November 4, 2023. Meeting topics included digital health; metrics of glycemia; the integration of glucose and insulin data into the electronic health record; technologies for insulin pumps, blood glucose monitors, and continuous glucose monitors; diabetes drugs and analytes; skin physiology; regulation of diabetes devices and drugs; and data science, artificial intelligence, and machine learning. A live demonstration of a personalized carbohydrate dispenser for people with diabetes was presented.

Lipodystrophy in methylmalonic acidemia associated with elevated FGF21 and abnormal methylmalonylation.

A distinct adipose tissue distribution pattern was observed in patients with methylmalonyl-CoA mutase deficiency, an inborn error of branched-chain amino acid (BCAA) metabolism, characterized by centripetal obesity with proximal upper and lower extremity fat deposition and paucity of visceral fat, that resembles familial multiple lipomatosis syndrome. To explore brown and white fat physiology in methylmalonic acidemia (MMA), body composition, adipokines, and inflammatory markers were assessed in 46 patients with MMA and 99 matched controls. Fibroblast growth factor 21 levels were associated with acyl-CoA accretion, aberrant methylmalonylation in adipose tissue, and an attenuated inflammatory cytokine profile. In parallel, brown and white fat were examined in a liver-specific transgenic MMA mouse model (Mmut-/- TgINS-Alb-Mmut). The MMA mice exhibited abnormal nonshivering thermogenesis with whitened brown fat and had an ineffective transcriptional response to cold stress. Treatment of the MMA mice with bezafibrates led to clinical improvement with beiging of subcutaneous fat depots, which resembled the distribution seen in the patients. These studies defined what we believe to be a novel lipodystrophy phenotype in patients with defects in the terminal steps of BCAA oxidation and demonstrated that beiging of subcutaneous adipose tissue in MMA could readily be induced with small molecules.

Does Wrist-Worn Accelerometer Wear Compliance Wane over a Free-Living Assessment Period? An NHANES Analysis.

PURPOSE: Accelerometers are used to objectively measure physical behaviors in free-living environments, typically for seven consecutive days or more. We examined whether participants experience "wear fatigue," a decline in wear time day over day, during typical assessment period acquired in a nationally representative sample of 6- to 80-yr-olds in the United States. METHODS: Participants were instructed to wear an ActiGraph GT3X+ on their nondominant wrist continuously for seven consecutive days. Participants with seven complete days of recorded data, regardless of wear status, were included in the analyses ( N = 13,649). Wear was scored with the sleep, wake, and nonwear algorithm. RESULTS: Participants averaged 1248 ± 3.6 min·d -1 (mean ± SE) of wear over the assessment, but wear time linearly decreased from day 1 (1295 ± 3.2 min) to day 7 (1170 ± 5.3 min), resulting in a wear fatigue of -18.1 ± 0.7 min·d -1 ( ß ± SE). Wear fatigue did not differ by sex but varied by age-group-highest in adolescents (-26.8 ± 2.4 min·d -1 ) and lowest in older adults (-9.3 ± 0.9 min·d -1 ). Wear was lower in evening (1800-2359 h) and early morning (0000-0559 h) compared with the middle of the day and on weekend days compared with weekdays. We verified similar wear fatigue (-23.5 ± 0.7 min·d -1 ) in a separate sample ( N = 14,631) with hip-worn devices and different wear scoring. Applying minimum wear criteria of ≥10 h·d -1 for ≥4 d reduced wear fatigue to -5.3 and -18.7 min·d -1 for the wrist and hip, respectively. CONCLUSIONS: Patterns of wear suggest noncompliance may disproportionately affect estimates of sleep and sedentary behavior, particularly for adolescents. Further study is needed to determine the effect of wear fatigue on longer assessments.

Dietary linoleic acid lowering alone does not lower arachidonic acid or endocannabinoids among women with overweight and obesity: A randomized, controlled trial.

The linoleic acid (LA)-arachidonic acid (ARA)-inflammatory axis suggests dietary LA lowering benefits health because it lowers ARA and ARA-derived endocannabinoids (ECB). Dietary LA reduction increases concentrations of omega-3 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and DHA derived ECB. The aim of this study was to examine targeted reduction of dietary LA, with and without EPA and DHA, on plasma EPA and DHA and ECB (2-arachidonoyl glycerol [2-AG], anandamide [AEA], and docosahexaenoyl ethanolamide [DHA-EA]). Healthy, pre-menopausal women (n = 62, BMI 30 ± 3 kg/m2 , age 35 ± 7 years; mean ± SD) were randomized to three 12-week controlled diets: (1) high LA, low omega-3 EPA and DHA (H6L3); (2) low LA, low omega-3 EPA and DHA (L6L3); or (3) low LA, high omega-3 EPA and DHA (L6H3). Baseline plasma fatty acids and ECB were similar between diets. Starting at 4 weeks, L6L3 and L6H3 lowered plasma LA compared to H6L3 (p < 0.001). While plasma ARA changed from baseline by 8% in L6L3 and -8% in L6H3, there were no group differences. After 4 weeks, plasma EPA and DHA increased from baseline in women on the L6H3 diet (ps < 0.001) and were different than the H6L3 and L6L3 diets. No differences were found between diets for AEA or 2-AG, however, in L6L3 and L6H3, AEA increased by 14% (ps < 0.02). L6H3 resulted in 35% higher DHA-EA (p = 0.013) whereas no changes were seen with the other diets. Lowering dietary LA did not result in the expected changes in fatty acids associated with the LA-ARA inflammatory axis in women with overweight and obesity.

Independent and Interactive Associations of Subjective and Objective Socioeconomic Status With Body Composition and Parent-Reported Hyperphagia Among Children.

Background: Subjective socioeconomic status (SSES) and objective socioeconomic status (OSES) have been independently associated with body composition and eating behavior in children. While low OSES may constrain access to healthier foods, low SSES has been associated with increased preference for and motivation to consume higher energy foods and portions independent of OSES. Despite these distinct ways that OSES and SSES may affect children's eating behavior and adiposity, their joint contributions remain unclear. We investigated the independent and interactive associations of SSES and OSES with children's BMI, fat mass index (FMI), and caregiver-reported hyperphagia. Methods: Data were derived from the Children's Growth and Behavior Study, an ongoing observational study. Multiple linear regressions used child's SSES and OSES of the family as independent factors and modeled the statistical interaction of SSES and OSES with BMI (n = 128), FMI (n = 122), and hyperphagia and its subscales (n = 76) as dependent variables. Results: SSES was independently and negatively associated with hyperphagia severity and OSES was independently and negatively associated with both FMI and hyperphagia severity. There was a statistical interaction effect of SSES and OSES on hyperphagia severity-lower SSES was associated with greater hyperphagia severity only at lower levels of OSES. Conclusions: These findings demonstrate a relationship between low OSES and child adiposity and that the relationship between child SSES and hyperphagia severity may be most relevant for children from households with lower family OSES. Future research on socioeconomic disparities in children's body composition and eating behaviors should examine the interaction of SSES and OSES. Clinical Trial Registration: NCT02390765.

Glycemia and Gluconeogenesis with Metformin and Liraglutide: A Randomized Trial in Youth-onset Type 2 Diabetes.

OBJECTIVE: Elevated rates of gluconeogenesis are an early pathogenic feature of youth-onset type 2 diabetes (Y-T2D), but targeted first-line therapies are suboptimal, especially in African American (AA) youth. We evaluated glucose-lowering mechanisms of metformin and liraglutide by measuring rates of gluconeogenesis and ß-cell function after therapy in AA Y-T2D. METHODS: In this parallel randomized clinical trial, 22 youth with Y-T2D: age 15.3±2.1y (mean±SD), 68% female, BMI 40.1±7.9kg/m2, duration of diagnosis 1.8±1.3y were randomized to metformin alone (Met) or metformin+liraglutide (Met+Lira) and evaluated before and after 12 weeks. Stable isotope tracers were used to measure gluconeogenesis [2H2O] and glucose production [6,6-2H2]glucose after an overnight fast and during a continuous meal. ß-cell function (sigma) and whole-body insulin sensitivity (mSI) were assessed during a frequently sampled 2h-OGTT. RESULTS: At baseline, gluconeogenesis, glucose production, and fasting and 2h glucose were comparable in both groups, though Met+Lira had higher HbA1c. Met+Lira had a greater decrease from baseline in fasting glucose (-2.0±1.3 vs. -0.6±0.9 mmol/L, P=0.008) and a greater increase in sigma (0.72±0.68 vs. -0.05±0.71, P=0.03). The change in fractional gluconeogenesis was similar between groups (Met+Lira: -0.36±9.4 vs. Met: 0.04±12.3%, P=0.9) and there were no changes in prandial gluconeogenesis or mSI. Increased glucose clearance in both groups was related to sigma (r=0.63, P=0.003) but not gluconeogenesis or mSI. CONCLUSIONS: Among Y-T2D, metformin with or without liraglutide improved glycemia but did not suppress high rates of gluconeogenesis. Novel therapies that will enhance ß-cell function and target the elevated rates of gluconeogenesis in Y-T2D are needed.

Associations of food reinforcement and food- related inhibitory control with adiposity and weight gain in children and adolescents.

Some, but not all studies have reported that, among youth with disordered eating and high weight, the relative reinforcing value of food (RRV-F, i.e., how hard a person will work for a high-energy-dense food when another reward is available) is greater, and food-related inhibitory control (i.e., ability to withhold a response to food-related stimuli) is lower, compared to peers without disordered eating or overweight. In most studies, high RRV-F and low food-related inhibitory control have been studied separately, as independent factors, with each suggested to predict excess weight and adiposity (fat mass) gain. We hypothesized that the interaction of these factors would prospectively exacerbate risk for weight and adiposity (fat mass) gain three years later in a sample of healthy youth. At baseline, RRV-F was measured using a Behavior Choice Task with the rewards being standardized servings of chocolate candies, cheese crackers, or fruit snacks. Food-related inhibitory control was determined by performance in response to food and non-food stimuli during a Food Go/No-Go task. At baseline and 3-year visits, total body adiposity was measured by dual-energy X-ray absorptiometry (DXA) and body mass index (BMI) was obtained using measured weight and height. A linear regression was conducted with 3-year adiposity as the dependent variable. RRV-F, food-related inhibitory control, and the RRV-F x food-related inhibitory control interaction as independent variables. Baseline adiposity, age, height, sex, race/ethnicity, and days between visits were included as covariates for model predicting 3-year adiposity. Baseline BMI, age, sex, race/ethnicity, and days between visits were included as covariates for model predicting 3-year BMI. One-hundred and nine youth (mean 12.4±2.7y, mean 0.50±1.02 BMIz, 30.3% with overweight/obesity, 45.9% female, 51.4% non-Hispanic White), 8-17 years at baseline, were studied. Baseline food-related inhibitory control (ßunstandardized = 0.33, p = .037, 95% CI [.02, 0.64]), but not baseline RRV-F (ßunstandardized = -0.003, p = .914), 95% CI [-0.05, 0.05]) was significantly associated with 3-year adiposity such that those with the poorest food-related inhibitory control (great number of commision errors) had the greatest adiposity gain. The interaction between RRV-F and food-related inhibitory control did not predict 3-year adiposity (ßunstandardized = -0.07, p = .648, 95% CI [-0.39, 0.25]). The pattern of findings was the same for models examining non-food related inhibitory control. Neither baseline food-related inhibitory control (ßunstandardized = 2.16, p = .256, 95% CI [-1.59, 5.92]), baseline RRV-F (ßunstandardized = 0.14, p = .660, 95% CI [-0.48, 0.75]), nor their interaction (ßunstandardized = -1.18, p = .547, 95% CI [-5.04, 2.69]) were significantly associated with 3-year BMI. However, non-food related inhibitory control (ßunstandardized = 0.54, p = .038, 95% CI [.22, 7.15]) was significantly associated with 3-year BMI. In summary, food-related inhibitory control but not RRV-F, was associated with changes in adiposity in a sample of children and adolescents. Among generally healthy youth, food-related inhibitory control may be a more relevant risk factor than food reinforcement for adiposity gain. Additional data are needed to determine how inhibitory control and reward systems, as well as other disinhibited eating behaviors/traits, may interact to promote excess weight gain over time in youth.

The Complex Effects of Light on Metabolism in Humans.

Light is an essential part of many life forms. The natural light-dark cycle has been the dominant stimulus for circadian rhythms throughout human evolution. Artificial light has restructured human activity and provided opportunities to extend the day without reliance on natural day-night cycles. The increase in light exposure at unwanted times or a reduced dynamic range of light between the daytime and nighttime has introduced negative consequences for human health. Light exposure is closely linked to sleep-wake regulation, activity and eating patterns, body temperature, and energy metabolism. Disruptions to these areas due to light are linked to metabolic abnormalities such as an increased risk of obesity and diabetes. Research has revealed that various properties of light influence metabolism. This review will highlight the complex role of light in human physiology, with a specific emphasis on metabolic regulation from the perspective of four main properties of light (intensity, duration, timing of exposure, and wavelength). We also discuss the potential influence of the key circadian hormone melatonin on sleep and metabolic physiology. We explore the relationship between light and metabolism through circadian physiology in various populations to understand the optimal use of light to mitigate short and long-term health consequences.

Physical Activity Levels (PAL) in US Adults-2019.

PURPOSE: Physical activity levels (PAL) are associated with mortality risk and were instrumental in estimating national energy requirements, but we are unaware of population-based estimates of PAL in US adults. Thus, we conducted a nationwide survey using a validated previous-day recall method to estimate PAL and the behavioral determinants of low and higher PAL. METHODS: Participants from the AmeriSpeak panel 20-75 yr of age ( N = 2640) completed Activities Completed over Time in 24-hours previous-day recalls. PAL values were estimated as the average metabolic equivalent value over 24 h. Recalls were conducted on randomly selected days in October and November 2019. Survey sample design weights were applied to reflect the US population. RESULTS: Mean age was 45.3 yr, 51% were female, 67% were non-Hispanic White, and 37% had a body mass index of ≥30 kg·m -2 . US adults reported a mean PAL of 1.63 (95% confidence interval, 1.60-1.65), and 39% (37%-42%) of adults reported PAL ≥1.6 on a given day. Men reported higher PAL than women (1.67 vs 1.59), and older adults reported lower PAL. Adults with PAL <1.4 spent 81% (12.1 h·d -1 ) of their waking day sedentary and 19% (2.7 h·d -1 ) in total physical activity. Adults with PAL considered to be "active"(1.6-1.89) spent only 49% (8.0 h·d -1 ) of their waking day sedentary, and 51% (8.3 h·d -1 ) physically active. CONCLUSIONS: Our study provides novel estimates of PAL in a nationwide sample of US adults and a description of the type and intensity of sedentary and physically active behaviors contributing to low and higher PAL. These findings may inform public health messages aimed at increasing physical activity in adults and potentially contribute to obesity prevention efforts.

A Glycemia Risk Index (GRI) of Hypoglycemia and Hyperglycemia for Continuous Glucose Monitoring Validated by Clinician Ratings.

BACKGROUND: A composite metric for the quality of glycemia from continuous glucose monitor (CGM) tracings could be useful for assisting with basic clinical interpretation of CGM data. METHODS: We assembled a data set of 14-day CGM tracings from 225 insulin-treated adults with diabetes. Using a balanced incomplete block design, 330 clinicians who were highly experienced with CGM analysis and interpretation ranked the CGM tracings from best to worst quality of glycemia. We used principal component analysis and multiple regressions to develop a model to predict the clinician ranking based on seven standard metrics in an Ambulatory Glucose Profile: very low-glucose and low-glucose hypoglycemia; very high-glucose and high-glucose hyperglycemia; time in range; mean glucose; and coefficient of variation. RESULTS: The analysis showed that clinician rankings depend on two components, one related to hypoglycemia that gives more weight to very low-glucose than to low-glucose and the other related to hyperglycemia that likewise gives greater weight to very high-glucose than to high-glucose. These two components should be calculated and displayed separately, but they can also be combined into a single Glycemia Risk Index (GRI) that corresponds closely to the clinician rankings of the overall quality of glycemia (r = 0.95). The GRI can be displayed graphically on a GRI Grid with the hypoglycemia component on the horizontal axis and the hyperglycemia component on the vertical axis. Diagonal lines divide the graph into five zones (quintiles) corresponding to the best (0th to 20th percentile) to worst (81st to 100th percentile) overall quality of glycemia. The GRI Grid enables users to track sequential changes within an individual over time and compare groups of individuals. CONCLUSION: The GRI is a single-number summary of the quality of glycemia. Its hypoglycemia and hyperglycemia components provide actionable scores and a graphical display (the GRI Grid) that can be used by clinicians and researchers to determine the glycemic effects of prescribed and investigational treatments.

Effects of interrupting daily sedentary behavior on children's glucose metabolism: A 6-day randomized controlled trial.

BACKGROUND: Metabolic disease risk in youth is influenced by sedentary behaviors. Acute in-lab studies show that, during a single day, interrupting a sedentary period with short bouts of physical activity improves glucometabolic outcomes. OBJECTIVE: To determine if acutely improved glucose metabolism persists after multi-day interruptions of sitting with walking brief bouts. We hypothesized that children who underwent interrupting sitting on multiple days would demonstrate lower insulin area under the curve during an oral glucose tolerance test compared to uninterrupted sitting. METHODS: Healthy, normoglycemic children (N = 109) ages 7-11 years were randomized to one of two conditions: Control (3 h of daily Uninterrupted Sitting) or Interrupted Sitting (3-min of moderate-intensity walking every 30 min for 3 h daily); with dietary intake controlled through provision of foodstuffs for the entire experiment. Participants attended six consecutive daily visits at a research ambulatory unit. The primary outcome was insulin area under the curve during the oral glucose tolerance test on day 6 during interrupted or uninterrupted sitting; secondary outcomes included glucose and c-peptide area under the curve, energy intake at a buffet meal on day 6, and free-living activity. RESULTS: Among 93 children (42 uninterrupted sitting, 51 interrupted sitting), daily interrupted sitting resulted in 21% lower insulin (ß = 0.102 CI:0.032-0.172, p = 0.005) and a 10% lower C-peptide (ß = 0.043, CI:0.001-0.084, p = 0.045) area under the curve. Matsuda and Glucose Effectiveness Indices were also improved (p's < 0.05). There were no group differences in energy intake or expenditure. CONCLUSIONS: Sustained behavioral change by interrupting sedentary behaviors is a promising intervention strategy for improving metabolic risk in children.

Examining cognitive-behavioral therapy change mechanisms for decreasing depression, weight, and insulin resistance in adolescent girls at risk for type 2 diabetes.

OBJECTIVE: Depression in adolescence is linked to risk for type 2 diabetes (T2D). In this secondary data analysis of a randomized controlled trial comparing cognitive-behavioral therapy (CBT) to a control program to ameliorate insulin resistance via reducing depression symptoms, we examine which CBT change mechanisms (e.g., behavioral activation, cognitive restructuring) contributed to decreased depression and subsequent improvements in body mass index (BMI), percent body fat, and insulin resistance. METHODS: Girls 12-17y with overweight/obesity and family history of T2D were randomized to six-week group CBT (n = 61) or health education (HealthEd; n = 58). At baseline and post-treatment, adolescents completed questionnaires assessing activities, thoughts, and depression symptoms. At baseline, post-treatment, and one-year, BMI was calculated and insulin outcomes were derived from two-hour oral glucose tolerance testing. At baseline and one-year, percent body fat was assessed with dual-energy x-ray absorptiometry. Indirect effects of CBT components were tested on one-year changes in BMI, percent body fat, and insulin indices through decreases in depression symptoms during treatment. Intervention was tested as a moderator. RESULTS: In CBT, but not HealthEd, there was an indirect effect of increased physical activity during treatment on decreased one-year BMI via reductions in depression symptoms during treatment. Also, there were conditional indirect effects in CBT of increased pleasantness of physical and social activity during treatment on decreased one-year BMI via decreased depression symptoms during treatment. CONCLUSION: Behavioral activation may be a useful intervention to decrease depression and reduce excess weight gain in the targeted prevention of T2D in at-risk adolescent girls. NCT01425905, clinicaltrials.gov.

Postprandial Plasma Lipidomics Reveal Specific Alteration of Hepatic-derived Diacylglycerols in Nonalcoholic Fatty Liver Disease.

BACKGROUND & AIMS: Hepatic energy metabolism is a dynamic process modulated by multiple stimuli. In nonalcoholic fatty liver disease (NAFLD), human studies typically focus on the static fasting state. We hypothesized that unique postprandial alterations in hepatic lipid metabolism are present in NAFLD. METHODS: In a prospective clinical study, 37 patients with NAFLD and 10 healthy control subjects ingested a standardized liquid meal with pre- and postprandial blood sampling. Postprandial plasma lipid kinetics were characterized at the molecular lipid species level by untargeted lipidomics, cluster analysis, and lipid particle isolation, then confirmed in a mouse model. RESULTS: There was a specific increase of multiple plasma diacylglycerol (DAG) species at 4 hours postprandially in patients with NAFLD but not in controls. This was replicated in a nonalcoholic steatohepatitis mouse model, where postprandial DAGs increased in plasma and concomitantly decreased in the liver. The increase in plasma DAGs appears early in the disease course, is dissociated from NAFLD severity and obesity, and correlates with postprandial insulin levels. Immunocapture isolation of very low density lipoprotein in human samples and stable isotope tracer studies in mice revealed that elevated postprandial plasma DAGs reflect hepatic secretion of endogenous, rather than meal-derived lipids. CONCLUSIONS: We identified a selective insulin-related increase in hepatic secretion of endogenously derived DAGs after a mixed meal as a unique feature of NAFLD. DAGs are known to be lipotoxic and associated with atherosclerosis. Although it is still unknown whether the increased exposure to hepatic DAGs contributes to extrahepatic manifestations and cardiovascular risk in NAFLD, our study highlights the importance of extending NAFLD research beyond the fasting state.

Activating Human Adipose Tissue with the ß3-Adrenergic Agonist Mirabegron.

An appealing strategy for treatment of metabolic disease in humans is activation of brown adipose tissue (BAT), a thermogenic organ best visualized through 18F-FDG PET/CT. BAT has been activated to varying degrees by mild cold exposure. However, this approach can cause undesirable stress, and there remains no consensus protocol. Here, we describe standardized methods for both acute and chronic activation of BAT using the orally administered ß3-adrenergic receptor (AR) agonist, mirabegron. Acute pharmacological stimulation has enabled quantification of whole-body BAT volume and metabolic activity using PET/CT imaging, and chronic stimulation increases these properties of BAT over time.

Screen Time and Body Image in Icelandic Adolescents: Sex-Specific Cross-Sectional and Longitudinal Associations.

Studies of adolescent body image and screen use are mostly limited to girls, and longitudinal data are scarce. We examined cross-sectional and longitudinal associations between these variables in mid-adolescent boys and girls. Data was collected when participants were at age 15 and 17, by questionnaire and objective measurements (n = 152 had complete data). Sex-specific linear regression was used to explore cross-sectional and longitudinal associations of self-reported screen use (total use, and time spent in gaming, TV/DVD/internet-based watching and internet use for communication) and body image, adjusting for vigorous physical activity, symptoms of depression, and body composition. Screen time was negatively associated with body image at both time points, although more strongly at age 15, and for girls only. Gaming and TV/DVD/internet watching was more strongly associated with body image than internet use for communication. Girls with above median screen time at both ages had 14% lower body image score at age 17 than girls with below median screen time at both time points. Our results suggest that screen use is likely to play a role in the development of body dissatisfaction among adolescent females. Limiting screen time may, therefore, help to mitigate body dissatisfaction in adolescent girls.

Retrieval-induced forgetting in children and adolescents with and without obesity.

BACKGROUND/OBJECTIVES: Previous research indicates that youth with obesity exhibit deficits in executive functioning (EF), which often take the form of impaired response inhibition. One aspect of EF not previously studied in obesity is the adaptive process known as retrieval-induced forgetting (RIF), the suppression/inhibition of intrusive or non-target items by the retrieval of specific items from memory. The present study investigated if child or adolescent obesity disrupts the ability to inhibit retrieval of intrusive memories. SUBJECTS/METHODS: We compared the manifestation of RIF in children (ages 8-12) and adolescents (ages 13-18) as a function of their weight status and sex. We also evaluated the effects of these variables on simple recall of items from episodic memory under conditions where competition from intrusive items was reduced. RESULTS: Children with obesity did not demonstrate significant RIF, whereas RIF was exhibited by preteens without obesity and by teenage participants with- and without obesity (Weight Status × Age Group interaction p = 0.028). This pattern of results did not differ as a function of sex for either age group. No differences in episodic memory were found. Additional analyses using Age as continuous covariate (and not as a nominal group) comparing participants who exhibited RIF with those who did not, found that the no RIF group consumed fast-food meals more frequently (p = 0.024) and had higher percentages of total body adiposity and android fat compared to the RIF group (p's < 0.05). CONCLUSIONS: The findings expand what is known about the effects of childhood obesity on cognitive functioning, identify impaired RIF with specific behavioral and dietary factors and increased adiposity, and suggest the possibility that impairments in the ability to inhibit intrusive memories of food and eating may contribute to poor early-life weight control.