Weight management in young adults with type 1 diabetes: The advancing care for type 1 diabetes and obesity network sequential multiple assignment randomized trial pilot results.

AIMS: Co-management of weight and glycaemia is critical yet challenging in type 1 diabetes (T1D). We evaluated the effect of a hypocaloric low carbohydrate, hypocaloric moderate low fat, and Mediterranean diet without calorie restriction on weight and glycaemia in young adults with T1D and overweight or obesity. MATERIALS AND METHODS: We implemented a 9-month Sequential, Multiple Assignment, Randomized Trial pilot among adults aged 19-30 years with T1D for ≥1 year and body mass index 27-39.9 kg/m2 . Re-randomization occurred at 3 and 6 months if the assigned diet was not acceptable or not effective. We report results from the initial 3-month diet period and re-randomization statistics before shutdowns due to COVID-19 for primary [weight, haemoglobin A1c (HbA1c), percentage of time below range <70 mg/dl] and secondary outcomes [body fat percentage, percentage of time in range (70-180 mg/dl), and percentage of time below range <54 mg/dl]. Models adjusted for design, demographic and clinical covariates tested changes in outcomes and diet differences. RESULTS: Adjusted weight and HbA1c (n = 38) changed by -2.7 kg (95% CI -3.8, -1.5, P < .0001) and -0.91 percentage points (95% CI -1.5, -0.30, P = .005), respectively, while adjusted body fat percentage remained stable, on average (P = .21). Hypoglycaemia indices remained unchanged following adjustment (n = 28, P > .05). Variability in all outcomes, including weight change, was considerable (57.9% were re-randomized primarily due to loss of <2% body weight). No outcomes varied by diet. CONCLUSIONS: Three months of a diet, irrespective of macronutrient distribution or caloric restriction, resulted in weight loss while improving or maintaining HbA1c levels without increasing hypoglycaemia in adults with T1D.

Mindfulness, disordered eating, and impulsivity in relation to glycemia among adolescents with type 1 diabetes and suboptimal glycemia from the Flexible Lifestyles Empowering Change (FLEX) intervention trial.

OBJECTIVE: To assess the relationship between mindfulness and glycemia among adolescents with type 1 diabetes (T1D) with suboptimal glycemia, and evaluate the potential mediation by ingestive behaviors, including disordered eating, and impulsivity. RESEARCH DESIGN AND METHODS: We used linear mixed models for hemoglobin A1c (HbA1c) and linear regression for continuous glucose monitoring (CGM) to study the relationship of mindfulness [Child and Adolescent Mindfulness Measure (CAMM)] and glycemia in adolescents with T1D from the 18-month Flexible Lifestyles Empowering Change (FLEX) trial. We tested for mediation of the mindfulness-glycemia relationship by ingestive behaviors, including disordered eating (Diabetes Eating Problem Survey-Revised), restrained eating, and emotional eating (Dutch Eating Behavior Questionnaire); and impulsivity (total, attentional, and motor, Barrett Impulsiveness Scale). RESULTS: At baseline, participants (n = 152) had a mean age of 14.9 ± 1.1 years and HbA1c of 9.4 ± 1.2% [79 ± 13 mmol/mol]. The majority of adolescents were non-Hispanic white (83.6%), 50.7% were female, and 73.0% used insulin pumps. From adjusted mixed models, a 5-point increase in mindfulness scores was associated with a -0.19% (95%CI -0.29, -0.08, p = 0.0006) reduction in HbA1c. We did not find statistically significant associations between mindfulness and CGM metrics. Mediation of the relationship between mindfulness and HbA1c by ingestive behaviors and impulsivity was not found to be statistically significant. CONCLUSIONS: Among adolescents with T1D and suboptimal glycemia, increased mindfulness was associated with lower HbA1c levels. Future studies may consider mindfulness-based interventions as a component of treatment for improving glycemia among adolescents with T1D, though more data are needed to assess feasibility and efficacy.

Alterations in ventral attention network connectivity in individuals with prediabetes.

Objective: Type 2 diabetes (T2D) is associated with aberrant neural functioning; however, the point at which brain function alterations occur in the progression of T2D is unknown. Here, we tested for differences in functional connectivity in adults with prediabetes and healthy individuals. We hypothesized that prediabetes, defined by glycated hemoglobin (HbA1c) 5.7-6.4% would be associated with disruptions in default mode network (DMN) connectivity. Methods: Fourteen brain networks were tested in 88 adults (prediabetes: n = 44; HbA1c = 5.8±0.2%; healthy: n = 44; HbA1c = 4.7±0.2%) matched for sex, age, and BMI. Results: We did not find differences in DMN connectivity between groups. Individuals with prediabetes showed stronger connectivity between the ventral attention network and (1) a visual network (p FWE = 0.0001); (2) a somatosensory network (p FWE = 0.0027). Individuals with healthy HbA1c showed stronger connectivity of the ventral attention network and (1) cingulo-opercular network (p FWE = 0.002); (2) a thalamic-striatal-visual network (p FWE = 0.001). Conclusions: Relative to individuals with prediabetes, those with a healthy HbA1c showed stronger connectivity between brain networks underlying self-control and attention to stimuli. In contrast, those with prediabetes demonstrated stronger connectivity between brain networks associated with sensory and attention to stimuli. While T2D reported contribute to decreased DMN connectivity, prediabetes is characterized by a shift in functional connectivity from a self-control network towards increasing connectivity in sensory network.

Reward-related eating, self-regulation, and weight change in pregnancy and postpartum: the Pregnancy Eating Attributes Study (PEAS).

BACKGROUND/OBJECTIVES: Reward-related eating is hypothesized to underlie risk for weight gain in obesogenic environments, but its role is unknown during pregnancy and postpartum when weight change is normative, but excess weight gain and weight retention are common. This study examined associations of self-reported reward-related eating, self-regulation, and the home food environment with excessive gestational weight gain (GWG) and postpartum weight change. SUBJECTS/METHODS: Participants in the Pregnancy Eating Attributes Study observational cohort were enrolled at ≤12 weeks pregnancy and followed through 1-year postpartum (458 recruited; 367 retained through delivery). Participants completed four measures of reward-related eating-Modified Yale Food Addiction Scale, Power of Food Scale, Multiple Choice Procedure, and a Reinforcing Value of Food Questionnaire; two measures of self-regulation-Barratt Impulsiveness Scale and Delay of Gratification Inventory; and a Home Food Inventory. Measured weight and skinfolds were obtained. Multinomial logistic and multiple linear regression analyses estimated associations of reward-related eating, self-regulation, and home food environment with excessive GWG, gestational fat gain, postpartum weight change, and percent of GWG retained. RESULTS: Excessive GWG was associated with food reinforcement intensity, but not with any other measure of reward-related eating, self-regulation, or home food environment. Greater gestational fat gain was associated only with higher Multiple Choice Procedure. Postpartum weight change and percent of GWG retained were associated with greater delay of gratification and obesogenic home food environment, but not with any measure of reward-related eating or with impulsivity. CONCLUSIONS: Findings do not support the hypothesis that self-reported reward-related eating is associated with weight outcomes in pregnancy and postpartum but indicate a relation of delay of gratification with postpartum weight retention. Further research using both surveys and objective measures of reward-related eating is needed to advance our understanding of the relation of reward-related eating with weight changes during this critical period of a woman's life.

Identification of clinically relevant dysglycemia phenotypes based on continuous glucose monitoring data from youth with type 1 diabetes and elevated hemoglobin A1c.

BACKGROUND/OBJECTIVE: To identify and characterize subgroups of adolescents with type 1 diabetes (T1D) and elevated hemoglobin A1c (HbA1c) who share patterns in their continuous glucose monitoring (CGM) data as "dysglycemia phenotypes." METHODS: Data were analyzed from the Flexible Lifestyles Empowering Change randomized trial. Adolescents with T1D (13-16 years, duration >1 year) and HbA1c 8% to 13% (64-119 mmol/mol) wore blinded CGM at baseline for 7 days. Participants were clustered based on eight CGM metrics measuring hypoglycemia, hyperglycemia, and glycemic variability. Clusters were characterized by their baseline features and 18 months changes in HbA1c using adjusted mixed effects models. For comparison, participants were stratified by baseline HbA1c (≤/>9.0% [75 mmol/mol]). RESULTS: The study sample included 234 adolescents (49.8% female, baseline age 14.8 ± 1.1 years, baseline T1D duration 6.4 ± 3.7 years, baseline HbA1c 9.6% ± 1.2%, [81 ± 13 mmol/mol]). Three Dysglycemia Clusters were identified with significant differences across all CGM metrics (P < .001). Dysglycemia Cluster 3 (n = 40, 17.1%) showed severe hypoglycemia and glycemic variability with moderate hyperglycemia and had a lower baseline HbA1c than Clusters 1 and 2 (P < .001). This cluster showed increases in HbA1c over 18 months (p-for-interaction = 0.006). No other baseline characteristics were associated with Dysglycemia Clusters. High HbA1c was associated with lower pump use, greater insulin doses, more frequent blood glucose monitoring, lower motivation, and lower adherence to diabetes self-management (all P < .05). CONCLUSIONS: There are subgroups of adolescents with T1D for which glycemic control is challenged by different aspects of dysglycemia. Enhanced understanding of demographic, behavioral, and clinical characteristics that contribute to CGM-derived dysglycemia phenotypes may reveal strategies to improve treatment.

Individual differences in appeal of energy dense foods predicts lower body mass change during adolescence.

Highly energy dense foods are often synonymous with high palatability, excess intake and weight gain. However, food preferences show individual differences. Food preferences are closely related to food intake, which can impact weight change over time. We examined whether the energy density of food images rated as appetizing and unappetizing foods related to baseline BMI and change in BMI over 3-year follow-up (n = 117; 45% Male, Baseline BMI: 21.1 ± 1.9. Participants completed hedonic visual analog scales (-100 to 100) ratings of 103 food images, and reported dietary intake at baseline, and had their height and weight directly measured over 3-year follow-up. Energy density (ED) of the food depicted in each image was calculated. For each participant, food images (kcal/g) were categorized into appetizing (32 images) and unappetizing foods (32 images) based on each individual's hedonic ratings. We observed significant interaction between energy density and hedonic value driven by an inverse relation between unappetizing food energy density and BMI change (p = 0.008). Specifically, participants who rated higher energy dense foods as unappetizing showed less weight gain (ß= -0.83; p = 0.00052). There was no significant relation between the energy density of appetizing foods and weight change (p = 0.67), suggesting that dislike of highly energy dense foods more strongly associates with lower weight gain than preference for low energy dense foods. Post-hoc analyses revealed that individuals with a higher preference for low energy density foods showed less weight gain over 3-years (ß = - 0.007, p = 0.02). Results support the idea that individual hedonic ratings for foods varying in energy density is a determinant of weight change in adolescents and may represent an important intervention target for obesity prevention programs.

Body mass variability is represented by distinct functional connectivity patterns.

Understanding weight-related differences in functional connectivity provides key insight into neurocognitive factors implicated in obesity. Here, we sampled three groups from human connectome project data: 1) 47 pairs of BMI-discordant twins (n = 94; average BMI-discordancy 6.7 ±â€¯3.1 kg/m2), 2) 47 pairs of gender and BMI matched BMI-discordant, unrelated individuals, and 3) 47 pairs of BMI-similar twins, to test for body mass dependent differences in between network functional connectivity. Across BMI discordant samples, three networks appeared to be highly sensitive to weight status; specifically, a network comprised of gustatory processing regions, a visual processing network, and the default mode network (DMN). Further, in the BMI-discordant twin sample, twins with lower BMI had stronger connectivity between striatal/thalamic and prefrontal networks (pFWE = 0.04). We also observed that individuals with a higher BMI than their twin had stronger connectivity between cerebellar and insular networks (pFWE = 0.04). Connectivity patterns observed in the BMI-discordant twin sample were not seen in a BMI-similar sample, providing evidence that the results are specific to BMI discordance. Beyond the involvement of gustatory and visual networks and the DMN, little overlap in results were seen between the two BMI-discordant samples. In concordance with previous findings, we hypothesize that stronger cortical-striatal-thalamic connectivity associated with lower body mass in twins may facilitate increased regulation of hedonically motivated behaviors. In twins with higher body mass, increased cerebellar-insula connectivity may be associated with compromised satiation signaling, an interpretation dovetailing prior research. The lack of overlapping results between the two BMI discordant samples may be a function of higher study design sensitivity in the BMI-discordant twin sample, relative to the more generalizable results in the unrelated sample. These findings demonstrate that distinct connectivity patterns can represent weight variability, adding to mounting evidence that implicates atypical brain functioning with the accumulation and/or maintenance of elevated weight.

Reward Region Responsivity Predicts Future Weight Gain and Moderating Effects of the TaqIA Allele.

Because no large prospective study has investigated neural vulnerability factors that predict future weight gain, we tested whether neural response to receipt and anticipated receipt of palatable food and monetary reward predicted body fat gain over a 3-year follow-up in healthy-weight adolescent humans and whether the TaqIA polymorphism moderates these relations. A total of 153 adolescents completed fMRI paradigms assessing response to these events; body fat was assessed annually over follow-up. Elevated orbitofrontal cortex response to cues signaling impending milkshake receipt predicted future body fat gain (r = 0.32), which is a novel finding that provides support for the incentive sensitization theory of obesity. Neural response to receipt and anticipated receipt of monetary reward did not predict body fat gain, which has not been tested previously. Replicating an earlier finding (Stice et al., 2008a), elevated caudate response to milkshake receipt predicted body fat gain for adolescents with a genetic propensity for greater dopamine signaling by virtue of possessing the TaqIA A2/A2 allele, but lower caudate response predicted body fat gain for adolescents with a genetic propensity for less dopamine signaling by virtue of possessing a TaqIA A1 allele, though this interaction was only marginal [p-value <0.05 corrected using voxel-level familywise error rate (pFWE) = 0.06]. Parental obesity, which correlated with TaqIA allele status (odds ratio = 2.7), similarly moderated the relation of caudate response to milkshake receipt to future body fat gain, which is another novel finding. The former interaction implies that too much or too little dopamine signaling and reward region responsivity increases risk for overeating, suggesting qualitatively distinct reward surfeit and reward deficit pathways to obesity. SIGNIFICANCE STATEMENT: Because no large prospective study has investigated neural vulnerability factors that predict future weight gain we tested whether neural response to receipt and anticipated receipt of palatable food and monetary reward predicted body fat gain over 3-year follow-up in healthy-weight adolescent humans and whether the TaqIA polymorphism moderates these relations. Elevated reward activation in response to food cues predicted future body fat gain. Elevated reward response to food receipt predicted body fat gain for adolescents with a TaqIA A2/A2 allele and lower reward response predicted body fat gain for those with a TaqIA A1 allele. Results imply that too much or too little dopamine signaling and reward region responsivity increases risk for overeating.

Hedonic Hunger Is Related to Increased Neural and Perceptual Responses to Cues of Palatable Food and Motivation to Consume: Evidence from 3 Independent Investigations.

BACKGROUND: The Power of Food Scale (PFS) seeks to identify individuals who experience high appetitive drive in response to food cues, which is a construct termed "hedonic hunger." OBJECTIVE: The purpose of this study was to assess cross-sectional correlates and predictive power of PFS scores to probe the construct of hedonic hunger. METHODS: Separate data from 3 studies (study 1, n = 44; study 2, n = 398; study 3, n = 100) were used to evaluate the construct of hedonic hunger. We examined the correlations between the PFS and neural responsivity during intake and anticipated intake of palatable foods, behavioral food reinforcement, perceptual hedonic ratings of food images, and change in body mass index (BMI) and binge eating over time. RESULTS: Hedonic hunger was strongly related to bilateral brain response in regions implicated in oral somatosensory processing during cue-elicited anticipation of food intake (study 1; right postcentral gyrus: r = 0.67, P < 0.001; left postcentral gyrus: r = 0.64, P < 0.001), and was correlated with behavioral food reinforcement (study 2; r = 0.31, P = 0.03) and perceptual hedonic ratings (study 3; r = 0.24, P = 0.02). Hedonic hunger was not associated with baseline BMI (studies 1-3: P = 0.14, 0.21, and 0.37, respectively) or change in BMI over the 2-y follow-up (studies 1 and 2: P = 0.14 and 0.37, respectively) but was significantly correlated with baseline binge eating in 2 samples (study 1: r = 0.58, P = 0.001; study 2: r = 0.31, P = 0.02; and study 3: P = 0.02). CONCLUSIONS: Hedonic hunger was not predictive of weight regulation. However, individuals who report high hedonic hunger are likely to show increased neural and perceptual responses to cues of palatable foods, increased motivation to consume such foods, and a greater likelihood of current binge eating.

Elevated BMI and Male Sex Are Associated with Greater Underreporting of Caloric Intake as Assessed by Doubly Labeled Water.

BACKGROUND: Inaccuracies in energy intake (EI) measurement hinder identification of risk factors that predict weight gain and evaluation of obesity prevention and treatment interventions. Research has used objective measures of EI to identify underreporting correlates, producing mixed results, suggesting the need to examine novel potential correlates. OBJECTIVE: With the use of an objective measure of EI from doubly labeled water (DLW) this report examined multiple potential underreporting correlates. METHODS: Adolescents from 2 studies (study 1, n = 91; mean age: 18.4 ± 0.58 y; 100% female; study 2, n = 162; mean age: 15.2 ± 1.99 y; 82 female adolescents; 80 male adolescents) completed a DLW assessment of EI, a food-frequency questionnaire, and measures of perceived pressure for thinness, thin-ideal internalization, body dissatisfaction, dieting, food-cue reactivity, eating disorder symptoms, socioeconomic status, and neural response to food; BMI (in kg/m(2)) was measured over a 2-y follow-up. RESULTS: Elevated BMI correlated with underreported EI in study 1 (r = 0.26, P < 0.05) and study 2 (r = 0.20, P = 0.01), as did male sex in study 2 (r = 0.24, P < 0.01); the other survey measures did not. Underreporting correlated negatively (r = -0.29; uncorr P < 0.001) with responsivity of brain regions implicated in motor control to palatable food receipt and positively (r = 0.31; uncorr P < 0.001) with responsivity of a region implicated in taste processing to cues signaling impending milkshake receipt. Underreporting did not predict future change in BMI in either study. CONCLUSIONS: Findings document marked underreporting and replicate evidence that BMI correlates positively with underreporting and extends this literature by revealing that several novel factors were unrelated to underreporting and further that neural responsivity to food correlated with underreporting, suggesting that adolescents who showed reduced responsivity in a motor control region to food receipt and elevated responsivity of gustatory regions to anticipated palatable food receipt showed greater underreporting. This trial was registered at clinicaltrials.gov as NCT00433680 and NCT02084836.

Brain-based etiology of weight regulation.

Caloric intake and energy balance are highly regulated to maintain metabolic homeostasis and weight. However, hedonic-motivated food intake, in particular consumption of highly rewarding foods, may act to override hemostatic signaling and contribute to overconsumption, weight gain, and obesity. Here, we review human neuroimaging literature that has delivered valuable insight into the neural correlates of hedonic-motivated ingestive behavior, weight gain, weight loss, and metabolic status. Our primary focus is the brain regions that are thought to encode aspects of food hedonics, gustatory and somatosensory processing, and executive functioning. Further, we discuss the variability of regional brain response as a function of obesity, weight gain, behavioral and surgical weight loss, as well as in type 2 diabetes.

Greater striatopallidal adaptive coding during cue-reward learning and food reward habituation predict future weight gain.

Animal experiments indicate that after repeated pairings of palatable food receipt and cues that predict palatable food receipt, dopamine signaling increases in response to predictive cues, but decreases in response to food receipt. Using functional MRI and mixed effects growth curve models with 35 females (M age=15.5±0.9; M BMI=24.5±5.4) we documented an increase in BOLD response in the caudate (r=.42) during exposure to cues predicting impending milkshake receipt over repeated exposures, demonstrating a direct measure of in vivo cue-reward learning in humans. Further, we observed a simultaneous decrease in putamen (r=-.33) and ventral pallidum (r=-.45) response during milkshake receipt that occurred over repeated exposures, putatively reflecting food reward habitation. We then tested whether cue-reward learning and habituation slopes predicted future weight over 2-year follow-up. Those who exhibited the greatest escalation in ventral pallidum responsivity to cues and the greatest decrease in caudate response to milkshake receipt showed significantly larger increases in BMI (r=.39 and -.69 respectively). Interestingly, cue-reward learning propensity and food reward habituation were not correlated, implying that these factors may constitute qualitatively distinct vulnerability pathways to excess weight gain. These two individual difference factors may provide insight as to why certain people have shown obesity onset in response to the current obesogenic environment in western cultures, whereas others have not.

Using participant hedonic ratings of food images to construct data driven food groupings.

Little is known regarding how individuals' hedonic ratings of a variety of foods interrelate and how hedonic ratings correspond to habitual dietary intake. Participant ratings of food appeal of 104 food images were collected while participants were in a fed state (n = 129). Self-reported frequency of intake of the food items, perceived hunger, body mass index (BMI), and dietary restraint were also assessed. Principal components analysis (PCA) was employed to analyze hedonic ratings of the foods, to identify component structures and to reduce the number of variables. The resulting component structures comprised 63 images loading on seven components including Energy-Dense Main Courses, Light Main Courses and Seafood as well as components more analogous to traditional food groups (e.g., Fruits, Grains, Desserts, Meats). However, vegetables were not represented in a unique, independent component. All components were positively correlated with reported intake of the food items (r's = .26-.52, p <.05), except for the Light Main Course component (r = .10). BMI showed a small positive relation with aggregated food appeal ratings (r = .19; p <.05), which was largely driven by the relations between BMI and appeal ratings for Energy-Dense Main Courses (r = .24; p <.01) and Desserts (r = .27; p <.01). Dietary restraint showed a small significant negative relation to Energy-Dense Main Courses (r = -.21; p <.05), and Meats (r = -.18; p <.05). The present investigation provides novel evidence regarding how individuals' hedonic ratings of foods aggregate into food components and how these component ratings relate to dietary intake. The notable absence of a vegetable component suggests that individuals' liking for vegetables is highly variable and, from an empirical standpoint, not related to how they respond hedonically to other food categories.

Energy expenditure during nutritional rehabilitation: a scoping review to investigate hypermetabolism in individuals with anorexia nervosa.

BACKGROUND: Weight gain and nutritional rehabilitation are essential first steps to achieve medical stabilization in anorexia nervosa, and frequent resistance to weight gain requires patients to consume high kilocalorie loads. Adaptive hypometabolism is common when patients begin treatment, and rebound hypermetabolism is suspected to be a significant barrier to weight gain. The aim of this review was to summarize existing data describing metabolic changes in anorexia nervosa during weight restoration. The reported findings challenge current hypotheses of weight gain resistance and highlight key areas for future research. METHODS: Using scoping review guidelines, three databases were searched for studies investigating metabolic changes in anorexia nervosa before and after renourishment. Two reviewers systematically screened the titles and abstracts of 447 articles, and full-text versions of 106 studies were assessed for eligibility. A total of 36 studies were included for review. Data regarding the study description, sample population (including age, weight, BMI, duration of treatment, and caloric intake), and metabolic variable descriptions were extracted. RESULTS: Female patients with anorexia nervosa from studies across 13 countries were included. Across the studies, average BMI increased from 13.7 kg/m2 at admission to 17.57 kg/m2. Patients presented to treatment with clinically reduced energy expenditure levels. After varying levels of nutritional rehabilitation and weight restoration, measured energy expenditure increased significantly in 76% of the studies. Energy expenditure values at the second timepoint increased to the standard range for normal weight female teenagers and adults. Despite these increases, the studies do not indicate the presence of a hypermetabolic state during renourishment. Additionally, all studies including both measured and predicted energy expenditure reported that predicted energy expenditure overestimated measured values. CONCLUSION: This study provides a detailed evaluation of the literature investigating energy expenditure and metabolic rate in patients with anorexia nervosa before and following a period of renourishment. The findings from this review identify important gaps in the current beliefs of energy expenditure in anorexia nervosa and highlight a need for further exploration of metabolic alterations during weight restoration.

Nutritional rehabilitation and weight restoration are two primary goals of anorexia nervosa treatment that pose significant physiological and psychological challenges for patients. Patients often require high caloric loads to continue an adequate weight gain trajectory, but the underlying cause of weight gain resistance remains unknown. We completed a scoping review of research into energy expenditure and metabolic rate during treatment. Our search identified 447 relevant articles from academic databases, and 106 were deemed eligible after screening. We extracted data, including sample characteristics, kilocalorie intake, energy expenditure, and treatment information, from 36 studies. When individuals arrived for treatment, their energy expenditure was lower than that of individuals without an eating disorder due to the prolonged state of nutrient deprivation. After varying amounts of time and kilocalorie intake, most studies reported significant increases in energy expenditure. However, energy expenditure after a period of renourishment did not indicate an overactive metabolism (i.e., "hypermetabolism"). Funders should consider supporting exploration of additional factors that may be functioning as barriers to weight gain during treatment, in pursuit of making treatment more efficient and long-lasting. Additionally, future research describing metabolism in anorexia nervosa should provide more consistent methodologies, robust statical testing, and comprehensive reporting of dietary intake.

Eating behaviors and estimated body fat percentage among adolescents with type 1 diabetes.

AIMS: Estimate associations between select eating behaviors and estimated body fat percentage (eBFP) and explore effect modification by sex among adolescents with type 1 diabetes (T1D). METHODS: This analysis included 257 adolescents (mean age 14.9 ± 1.14 years; 49.8 % female) with baseline hemoglobin A1c (HbA1c) between 8 and 13 % (64 mmol/mol-119 mmol/mol) from a randomized trial designed to improve glycemia. Eating behaviors and eBFP were determined from surveys and validated equations respectively. Linear mixed models were used to estimate associations. Effect modification was assessed via stratified plots, stratified associations, and interaction terms. RESULTS: Disordered eating, dietary restraint, and eBFP were significantly higher among females while external eating was higher among males. Disordered eating (ß: 0.49, 95 %CI: 0.24, 0.73, p = 0.0001) and restraint (ß: 1.11, 95 %CI: 0.29, 1.92, p = 0.0081) were positively associated with eBFP while external eating was not (ß: -0.19, 95 %CI: -0.470, 0.096, p = 0.20). Interactions with sex were not significant (p-value range: 0.28-0.64). CONCLUSION: Disordered eating and dietary restraint were positively associated with eBFP, highlighting the potential salience of these eating behaviors to cardiometabolic risk for both female and male adolescents. Prospective studies should investigate whether these eating behaviors predict eBFP longitudinally to inform obesity prevention strategies in T1D.

Multilocus genetic composite reflecting dopamine signaling capacity predicts reward circuitry responsivity.

The objective of the study was to test the hypotheses that humans with genotypes putatively associated with low dopamine (DA) signaling capacity, including the TaqIA A1 allele, DRD2-141C Ins/Ins genotype, DRD4 7-repeat or longer allele, DAT1 10-repeat allele, and the Met/Met COMT genotype, and with a greater number of these genotypes per a multilocus composite, show less responsivity of reward regions that primarily rely on DA signaling. Functional magnetic resonance imaging (fMRI) paradigms were used to investigate activation in response to receipt and anticipated receipt of palatable food and monetary reward. DNA was extracted from saliva using standard methods. Participants were 160 adolescents (mean age = 15.3 years, SD = 1.07 years; mean body mass index = 20.8, SD = 1.9). The main outcome was blood oxygenation level-dependent activation in the fMRI paradigms. Data confirmed that these fMRI paradigms activated reward, attention, somatosensory, and gustatory regions. Individuals with, versus without, these five genotypes did not show less activation of DA-based reward regions, but those with the Met/Met versus the Val/Val COMT genotype showed less middle temporal gyrus activation and those with the DRD4-L versus the DRD4-S genotype showed less middle occipital gyrus activation in response to monetary reward. Critically, the multilocus composite score revealed that those with a greater number of these genotypes showed less activation in reward regions, including the putamen, caudate, and insula, in response to monetary reward. The results suggest that the multilocus genetic composite is a more sensitive index of vulnerability for low reward region responsivity than individual genotypes.

Caloric deprivation increases responsivity of attention and reward brain regions to intake, anticipated intake, and images of palatable foods.

Dietary restraint theoretically increases risk for binge eating, but prospective and experimental studies have produced contradictory findings, apparently because dietary restraint scales do not identify individuals who are reducing caloric intake. Yet, experimentally manipulated caloric deprivation increases responsivity of brain regions implicated in attention and reward to food images, which may contribute to binge eating. We tested whether self-imposed acute and longer-term caloric restriction increases responsivity of attention and reward regions to images, anticipated receipt, and receipt of palatable food using functional magnetic resonance imaging among female and male adolescents (Study 1 n=34; Study 2 n=51/81). Duration of acute caloric deprivation correlated positively with activation in regions implicated in attention, reward, and motivation in response to images, anticipated receipt, and receipt of palatable food (e.g., anterior cingulate cortex, orbitofrontal cortex, putamen, and precentral gyrus respectively). Youth in a longer-term negative energy balance likewise showed greater activation in attention (anterior cingulate cortex, ventral medial prefrontal cortex), visual processing (superior visual cortex), reward (caudate) and memory (hippocampus) regions in response to receipt and anticipated receipt of palatable food relative to those in neutral or positive energy balance. Results confirm that self-imposed caloric deprivation increases responsivity of attention, reward, and motivation regions to food, which may explain why caloric deprivation weight loss diets typically do not produce lasting weight loss.

Food reinforcement architecture: A framework for impulsive and compulsive overeating and food abuse.

Few reward-based theories address key drivers of susceptibility to food cues and consumption beyond fullness. Decision-making and habit formation are governed by reinforcement-based learning processes that, when overstimulated, can drive unregulated hedonically motivated overeating. Here, a model food reinforcement architecture is proposed that uses fundamental concepts in reinforcement and decision-making to identify maladaptive eating habits that can lead to obesity. This model is unique in that it identifies metabolic drivers of reward and incorporates neuroscience, computational decision-making, and psychology to map overeating and obesity. Food reinforcement architecture identifies two paths to overeating: a propensity for hedonic targeting of food cues contributing to impulsive overeating and lack of satiation that contributes to compulsive overeating. A combination of those paths will result in a conscious and subconscious drive to overeat independent of negative consequences, leading to food abuse and/or obesity. Use of this model to identify aberrant reinforcement learning processes and decision-making systems that can serve as markers of overeating risk may provide an opportunity for early intervention in obesity.

Correlates of neural adaptation to food cues and taste: the role of obesity risk factors.

Identifying correlates of brain response to food cues and taste provides critical information on individual differences that may influence variability in eating behavior. However, a few studies examine how brain response changes over repeated exposures and the individual factors that are associated with these changes. Using functional magnetic resonance imaging, we examined how brain response to a palatable taste and proceeding cues changed over repeated exposures and how individual differences in weight, familial obesity risk, dietary restraint and reward responsiveness correlate with these changes. In healthy-weight adolescents (n = 154), caudate and posterior cingulate cortex (PCC) response increased with repeated cue presentations, and oral somatosensory cortex and insula response increased with repeated milkshake tastes. The magnitude of increase over exposures in the left PCC to cues was positively associated with body mass index percentile (r = 0.18, P = 0.026) and negatively associated with dietary restraint scores (r = -0.24, P = 0.003). Adolescents with familial obesity risk showed higher cue-evoked caudate response across time, compared to the low-risk group (r = 0.12, P = 0.035). Reward responsiveness positively correlated with right oral somatosensory cortex/insula response to milkshake over time (r = 0.19, P = 0.018). The results show that neural responses to food cues and taste change over time and that individual differences related to weight gain are correlated with these changes.