Relationships between physical activity, healthy eating and cortical thickness in children and young adults.

Prior neuroimaging studies have shown associations between healthy lifestyle factors and cortical thickness; however, results on the direction of this association have been inconsistent. While the majority of studies were performed in older adults within specific weight status categories, little has been reported in younger populations with a range of adiposity, including groups with healthy-weight, overweight, and obesity. Here we investigated relationships between indices of physical activity (PA) and healthy eating with cortical thickness in children and youth/young adults and examined whether these relationships differed by weight status and age groups. Study participants included 119 youth/young adults and 159 children. We hypothesized that greater levels of PA and/or healthy eating index (HEI) composite scores would be positively associated with cortical thickness, and that this association would differ in overweight or obese groups versus normal weight groups, as well as youth/young adults vs. child cohorts. Overall PA (minutes/day) was assessed using 24-hour PA recalls. HEI was calculated to assess diet quality. A structural MRI was performed, and FreeSurfer 6.0 was used to assess cortical thickness in 68 regions of interest (ROI). Mixed effects modeling was performed to investigate associations of PA or HEI with cortical thickness. FDR corrections were applied for multiple ROIs. PA was positively associated with cortical thickness in the caudal middle frontal cortex (FDR adjusted p = 0.042) and cuneus cortex (FDR adjusted p = 0.017) after controlling for sex, age group, and weight status. When stratified by age, in youth/young adults, higher time spent in PA was associated with greater cortical thickness in the frontal, temporal, parietal and occipital cortex, after adjusting for sex and weight group (FDR adjusted ps < 0.05). No significant associations between PA and cortical thickness were observed in children. No significant associations between PA and cortical thickness were observed when stratified by weight group. No significant associations between HEI and cortical thickness were observed. These results indicate that higher time spent in PA is associated with greater cortical thickness, a relationship that appears to be stronger during youth/young adulthood and may be related to more favorable brain health outcomes.

Associations Between Sleep and Metabolic Outcomes in Preadolescent Children.

Context: Growing evidence suggests an important role for sleep for the metabolic health of children. Objective: We aimed to determine how sleep is related to insulin sensitivity, insulin secretion, beta-cell function, and adiposity (BMI z-scores, body fat %, waist to height ratio) using objectively measured sleep and oral glucose tolerance test (OGTT)-derived measures. Methods: Sixty-two children aged 7-11 years, born at Kaiser Permanente Southern California, wore wrist accelerometers for 7 days to objectively measure sleep, completed an OGTT, and had anthropometric measures (height [cm], weight [kg], waist [cm], body fat [%]) collected. Using linear regression, associations between Matsuda insulin sensitivity index (ISI), insulinogenic index (IGI), disposition index (DI), BMI z-score, waist to height ratio, and body fat % with sleep parameters [total sleep time (TST; min), sleep efficiency (SE; %), time in bed (TIB; min), wake after sleep onset (WASO; min), and sleep latency (SL; min)] were assessed. Body fat % was tested as a mediator of the relationship between TST and ISI. Results: Longer TST was associated with better insulin sensitivity (P = 0.02), but not after adjusting for body fat %. Sleep parameters were not associated with IGI or DI. Longer TST was associated with lower % body fat (P = 0.01) and lower waist-to-height-ratios (P = 0.05). Body fat % explained 62% (P = 0.01) of the relationship between TST and ISI. Longer TIB was associated with lower adiposity measures (P < 0.05). There were no associations between SE, WASO, or SL and metabolic outcomes. Conclusion: Objectively measured sleep duration was associated with lower adiposity, and the relationship between sleep duration and ISI appeared partly through adiposity levels in preadolescent children. Longer sleep duration may be important for metabolic health.

FGF21 response to sucrose is associated with BMI and dorsal striatal signaling in humans.

OBJECTIVE: This study examined associations between BMI and dietary sugar intake with sucrose-induced fibroblast growth factor 21 (FGF21) and whether circulating FGF21 is associated with brain signaling following sucrose ingestion in humans. METHODS: A total of 68 adults (29 male; mean [SD), age 23.2 [3.8] years; BMI 27.1 [4.9] kg/m2 ) attended visits after a 12-hour fast. Plasma FGF21 was measured at baseline and at 15, 30, and 120 minutes after sucrose ingestion (75 g in 300 mL of water). Brain cerebral blood flow responses to sucrose were measured using arterial spin labeling magnetic resonance imaging. RESULTS: Higher circulating FGF21 levels were associated with reduced blood flow in the striatum in response to sucrose (ß = -7.63, p = 0.03). This association was greatest among persons with healthy weight (ß = -15.70, p = 0.007) and was attenuated in people with overweight (ß = -4.00, p = 0.63) and obesity (ß = -12.45, p = 0.13). BMI was positively associated with FGF21 levels in response to sucrose (ß = 0.53, p = 0.02). High versus low dietary sugar intake was associated with greater FGF21 responses to acute sucrose ingestion in individuals with healthy weight (ß = 8.51, p = 0.04) but not in individuals with overweight or obesity (p > 0.05). CONCLUSIONS: These correlative findings support evidence in animals showing that FGF21 acts on the brain to regulate sugar consumption through a negative feedback loop.

Brain responses to glucose ingestion are greater in children than adults and are associated with overweight and obesity.

OBJECTIVE: This study investigated whether brain regions involved in the regulation of food intake respond differently to glucose ingestion in children and adults and the relationship between brain responses and weight status. METHODS: Data included 87 children (ages 7-11 years) and 94 adults (ages 18-35 years) from two cohorts. Healthy weight, overweight, and obesity were defined by Centers for Disease Control and Prevention criteria. Brain responses to glucose were determined by measuring cerebral blood flow using arterial spin labeling magnetic resonance imaging in brain regions involved in the regulation of eating behavior. RESULTS: Children showed significantly larger increases in brain responses to glucose than adults in the dorsal striatum (p < 0.01), insula (p < 0.01), hippocampus (p < 0.01), and dorsal-lateral prefrontal cortex (p < 0.01). Responses to glucose in the dorsal striatum (odds ratio [OR] = 1.52, 95% CI 1.05-2.20; p = 0.03), hippocampus (OR = 1.51, 95% CI: 1.02-2.22; p = 0.04), insula (OR = 1.64, 95% CI: 1.11-2.42; p = 0.01), and orbitofrontal cortex (OR = 1.63 95% CI: 1.12-2.39; p = 0.01) were positively associated with overweight or obesity, independent of age group. CONCLUSIONS: Children have greater brain responses to glucose ingestion than adults in regions involved in eating behavior, and these responses are associated with weight status.

Obesity and Sex-Related Associations With Differential Effects of Sucralose vs Sucrose on Appetite and Reward Processing: A Randomized Crossover Trial.

Importance: Nonnutritive sweeteners (NNSs) are used as an alternative to nutritive sweeteners to quench desire for sweets while reducing caloric intake. However, studies have shown mixed results concerning the effects of NNSs on appetite, and the associations between sex and obesity with reward and appetitive responses to NNS compared with nutritive sugar are unknown. Objective: To examine neural reactivity to different types of high-calorie food cues (ie, sweet and savory), metabolic responses, and eating behavior following consumption of sucralose (NNS) vs sucrose (nutritive sugar) among healthy young adults. Design, Setting, and Participants: In a randomized, within-participant, crossover trial including 3 separate visits, participants underwent a functional magnetic resonance imaging task measuring blood oxygen level-dependent signal in response to visual cues. For each study visit, participants arrived at the Dornsife Cognitive Neuroimaging Center of University of Southern California at approximately 8:00 am after a 12-hour overnight fast. Blood was sampled at baseline and 10, 35, and 120 minutes after participants received a drink containing sucrose, sucralose, or water to measure plasma glucose, insulin, glucagon-like peptide(7-36), acyl-ghrelin, total peptide YY, and leptin. Participants were then presented with an ad libitum meal. Participants were right-handed, nonsmokers, weight-stable for at least 3 months before the study visits, nondieters, not taking medication, and with no history of eating disorders, illicit drug use, or medical diagnoses. Data analysis was performed from March 2020 to March 2021. Interventions: Participants ingested 300-mL drinks containing either sucrose (75 g), sucralose (individually sweetness matched), or water (as a control). Main Outcomes and Measures: Primary outcomes of interest were the effects of body mass index (BMI) status and sex on blood oxygen level-dependent signal to high-calorie food cues, endocrine, and feeding responses following sucralose vs sucrose consumption. Secondary outcomes included neural, endocrine, and feeding responses following sucrose vs water and sucralose vs water (control) consumption, and cue-induced appetite ratings following sucralose vs sucrose (and vs water). Results: A total of 76 participants were randomized, but 2 dropped out, leaving 74 adults (43 women [58%]; mean [SD] age, 23.40 [3.96] years; BMI range, 19.18-40.27) who completed the study. In this crossover design, 73 participants each received water (drink 1) and sucrose (drink 2), and 72 participants received water (drink 1), sucrose (drink 2), and sucralose (drink 3). Sucrose vs sucralose was associated with greater production of circulating glucose, insulin, and glucagon-like peptide-1 and suppression of acyl-ghrelin, but no differences were found for peptide YY or leptin. BMI status by drink interactions were observed in the medial frontal cortex (MFC; P for interaction < .001) and orbitofrontal cortex (OFC; P for interaction = .002). Individuals with obesity (MFC, ß, 0.60; 95% CI, 0.38 to 0.83; P < .001; OFC, ß, 0.27; 95% CI, 0.11 to 0.43; P = .002), but not those with overweight (MFC, ß, 0.02; 95% CI, -0.19 to 0.23; P = .87; OFC, ß, -0.06; 95% CI, -0.21 to 0.09; P = .41) or healthy weight (MFC, ß, -0.13; 95% CI, -0.34 to 0.07; P = .21; OFC, ß, -0.08; 95% CI, -0.23 to 0.06; P = .16), exhibited greater responsivity in the MFC and OFC to savory food cues after sucralose vs sucrose. Sex by drink interactions were observed in the MFC (P for interaction = .03) and OFC (P for interaction = .03) after consumption of sucralose vs sucrose. Female participants had greater MFC and OFC responses to food cues (MFC high-calorie vs low-calorie cues, ß, 0.21; 95% CI, 0.05 to 0.37; P = .01; MFC sweet vs nonfood cues, ß, 0.22; 95% CI, 0.02 to 0.42; P = .03; OFC food vs nonfood cues, ß, 0.12; 95% CI, 0.02 to 0.22; P = .03; and OFC sweet vs nonfood cues, ß, 0.15; 95% CI, 0.03 to 0.27; P = .01), but male participants' responses did not differ (MFC high-calorie vs low-calorie cues, ß, 0.01; 95% CI, -0.19 to 0.21; P = .90; MFC sweet vs nonfood cues, ß, -0.04; 95% CI, -0.26 to 0.18; P = .69; OFC food vs nonfood cues, ß, -0.08; 95% CI, -0.24 to 0.08; P = .32; OFC sweet vs nonfood cues, ß, -0.11; 95% CI, -0.31 to 0.09; P = .31). A sex by drink interaction on total calories consumed during the buffet meal was observed (P for interaction = .03). Female participants consumed greater total calories (ß, 1.73; 95% CI, 0.38 to 3.08; P = .01), whereas caloric intake did not differ in male participants (ß, 0.68; 95% CI, -0.99 to 2.35; P = .42) after sucralose vs sucrose ingestion. Conclusions and Relevance: These findings suggest that female individuals and those with obesity may be particularly sensitive to disparate neural responsivity elicited by sucralose compared with sucrose consumption. Trial Registration: ClinicalTrials.gov Identifier: NCT02945475.

Obesity and Dietary Added Sugar Interact to Affect Postprandial GLP-1 and Its Relationship to Striatal Responses to Food Cues and Feeding Behavior.

It has been hypothesized that the incretin hormone, glucagon-like peptide-1 (GLP-1), decreases overeating by influencing mesolimbic brain regions that process food-cues, including the dorsal striatum. We previously showed that habitual added sugar intake was associated with lower glucose-induced circulating GLP-1 and a greater striatal response to high calorie food cues in lean individuals. Less is known about how dietary added sugar and obesity may interact to affect postprandial GLP-1 and its relationship to striatal responses to food cues and feeding behavior. The current study aimed to expand upon previous research by assessing how circulating GLP-1 and striatal food cue reactivity are affected by acute glucose consumption in participants with varied BMIs and amounts of habitual consumption of added sugar. This analysis included 72 participants from the Brain Response to Sugar Study who completed two study visits where they consumed either plain water or 75g glucose dissolved in water (order randomized; both drinks were flavored with non-caloric cherry flavoring) and underwent repeated blood sampling, a functional magnetic resonance imaging (fMRI) based food-cue task, and an ad-libitum buffet meal. Correlations between circulating GLP-1 levels, striatal food-cue reactivity, and food intake were assessed, and interactions between obesity and added sugar on GLP-1 and striatal responses were examined. An interaction between BMI and dietary added sugar was associated with reduced post-glucose GLP-1 secretion. Participants who were obese and consumed high levels of added sugar had the smallest increase in plasma GLP-1 levels. Glucose-induced GLP-1 secretion was correlated with lower dorsal striatal reactivity to high-calorie versus low-calorie food-cues, driven by an increase in reactivity to low calorie food-cues. The increase in dorsal striatal reactivity to low calorie food-cues was negatively correlated with sugar consumed at the buffet. These findings suggest that an interaction between obesity and dietary added sugar intake is associated with additive reductions in postprandial GLP-1 secretion. Additionally, the results suggest that changes to dorsal striatal food cue reactivity through a combination of dietary added sugar and obesity may affect food consumption.

BMI status and associations between affect, physical activity and anxiety among U.S. children during COVID-19.

BACKGROUND: There is concern regarding how the COVID-19 pandemic may impact the psychological and physical health of children, but to date, studies on mental health during the pandemic in children are limited. Furthermore, unprecedented lifestyle stressors associated with the pandemic may aggravate the childhood obesity epidemic, but the role of BMI on child activity levels and psychological outcomes during COVID-19 is unknown. OBJECTIVES: We investigated how emotional responses (positive/negative affect), physical activity (PA) and sedentary behaviours related to anxiety among U.S. children with healthy weight and overweight/obesity during the pandemic. METHODS: Sixty-four typically developing children (63% girls, 53% healthy weight) aged 9 to 15 years completed two virtual visits during the height of 'stay-at-home' measures from April 22 to July 29, 2020. Children completed 24-hours PA recalls, state portion of State-Trait Anxiety Inventory for Children and the 10-item Positive and Negative Affect Schedule for Children. RESULTS: Independent of child BMI status, child anxiety scores were over five standard deviations greater than normative values from paediatric populations prior to the pandemic. Higher positive affect and PA were each associated with reduced anxiety levels in children with overweight/obesity, whereas higher positive affect was associated with reduced anxiety in children with healthy weight. Greater leisure screen time was associated with higher negative affect irrespective of child BMI status. CONCLUSIONS: These associations highlight the potential mental health benefits of maintaining positive affect, engaging in PA and limiting leisure screen time for children during the pandemic and suggest that these associations may be particularly relevant for children with overweight/obesity.

Appetite-Regulating Hormones Are Reduced After Oral Sucrose vs Glucose: Influence of Obesity, Insulin Resistance, and Sex.

CONTEXT: Fructose compared to glucose has adverse effects on metabolic function, but endocrine responses to oral sucrose vs glucose is not well understood. OBJECTIVE: We investigated how oral sucrose vs glucose affected appetite-regulating hormones, and how biological factors (body mass index [BMI], insulin sensitivity, sex) influence endocrine responses to these 2 types of sugar. DESIGN: Sixty-nine adults (29 men; 23.22 ±â€…3.74 years; BMI 27.03 ±â€…4.96 kg/m2) completed the study. On 2 occasions, participants consumed 300-mL drinks containing 75 g of glucose or sucrose. Blood was sampled at baseline, 10, 35, and 120 minutes post drink for plasma glucose, insulin, glucagon-like peptide (GLP-1)(7-36), peptide YY (PYY)total, and acyl-ghrelin measures. Hormone levels were compared between conditions using a linear mixed model. Interaction models were performed, and results were stratified to assess how biological factors influence endocrine responses. RESULTS: Sucrose vs glucose ingestion provoked a less robust rise in glucose (P < .001), insulin (P < .001), GLP-1 (P < .001), and PYY (P = .02), whereas acyl-ghrelin suppression was similar between the sugars. We found BMI status by sugar interactions for glucose (P = .01) and PYY (P = .03); obese individuals had smaller increases in glucose and PYY levels after consuming sucrose vs glucose. There were interactions between insulin sensitivity and sugar for glucose (P = .003) and insulin (P = .04), and a sex by sugar interaction for GLP-1 (P = .01); men demonstrated smaller increases in GLP-1 in response to oral sucrose vs glucose. CONCLUSION: Sucrose is less efficient at signaling postprandial satiation than glucose, and biological factors influence differential hormone responses to sucrose vs glucose consumption.

Prenatal exposure to gestational diabetes is associated with anxiety and physical inactivity in children during COVID-19.

BACKGROUND: The coronavirus disease 2019 (COVID-19) is associated with adverse child mental health outcomes and reduced physical activity. Moreover, prenatal exposure to gestational diabetes (GDM) is associated with increased risk for adverse psychological outcomes in children. OBJECTIVES: Assess prenatal exposure to GDM on anxiety levels and physical activity in children during the COVID-19 pandemic. METHODS: Sixty-five children age 9 to 15 reported their physical activity and anxiety levels using the 24-hours physical activity recall and the State-Trait Anxiety Inventory for Children via phone or video meetings. Prenatal exposure to GDM was obtained from maternal electronic medical records. RESULTS: The 38 GDM-exposed children reported significantly higher anxiety levels and were less likely to engage in any vigorous physical activity (VPA) (5% vs 30%) compared to the 27 GDM-unexposed children. Lower levels of physical activity were significantly associated with higher levels of anxiety. Less engagement in VPA explained 75% of the association between GDM exposure and anxiety levels. CONCLUSIONS: Engaging in physical activity during the COVID-19 pandemic may be beneficial for reducing anxiety, particularly amongst GDM-exposed children.

Associations between Affect, Physical Activity, and Anxiety Among US Children During COVID-19.

We investigated how emotional responses (positive and negative affect), physical activity (PA), and sedentary behaviors related to anxiety among US children during the COVID-19 pandemic. Sixty-four typically-developing children (63% girls) age 9-15 years old completed two virtual visits during height of "stay-at-home" measures between April 22 - July 29, 2020. Children completed 24-hour PA recalls, state portion of State-Trait Anxiety Inventory for Children (STAIC), and the shortened 10-item Positive and Negative Affect Schedule for Children (PANAS-C). Children reported state anxiety scores that were more than 5 standard deviations greater than values from healthy pediatric populations prior to the pandemic. Children with higher positive affect and who reported more time in PA reported less state anxiety. Sedentary and leisure screen time were positively correlated with negative affect. Our findings suggest that maintaining positive affect, engaging in PA, and limiting leisure screen time may be important for child mental health during stressful periods. STATEMENT OF RELEVANCE: There is increasing concern regarding how the COVID-19 pandemic may impact the psychological and physical health of children. To date, studies on mental health during the pandemic in children are limited. We investigated links between activity levels and psychological outcomes in children during the height of the "stay-at-home" measures. We found that children had anxiety scores that were more than 5 standard deviations greater than normative values from healthy pediatric populations prior to the pandemic, and 94% of children exceeded the American Academy of Pediatrics recommendations on leisure screen time. Positive affect and physical activity were associated with reduced anxiety levels in children during the pandemic. These findings highlight the important mental health benefits of maintaining positive affect, engaging in physical activity, and limiting leisure screen time for children, especially during stressful periods.

Children's Anxiety and Physical Activity during COVID-19 in Relation to Prenatal Exposure to Gestational Diabetes.

Research goal: Assess the relationships between anxiety levels, physical activity and in utero exposure to Gestational Diabetes mellitus (GDM) in children age 9 to 15, during the COVID-19 pandemic. METHODS: During the COVID-19 pandemic, participants completed phone call or video calls with study personnel where they were asked to report on their physical activity and anxiety levels using the 24-hour physical activity recall and the State-Trait Anxiety Inventory for Children. GDM-exposure was assessed using electronic medical records. RESULTS: Children who reported higher levels of moderate to vigorous physical activity or vigorous physical activity, reported lower anxiety symptoms. Children exposed to GDM in utero reported higher anxiety scores and lower engagement in vigorous physical activity compared to unexposed children. Moreover, the pathway through which children exposed to GDM in utero, reported higher anxiety was partially explained by reduced engagement in vigorous physical activity (75%, p=0.05). CONCLUSIONS: Engaging in physical activity during the COVID-19 pandemic may be beneficial for reducing anxiety, particularly among children exposed to GDM in utero, who are at increased risk for adverse psychological outcomes.