A gut reaction: Microbiome-driven glycemic effects of non-nutritive sweeteners.

Non-nutritive sweeteners are increasingly consumed to satisfy cravings for sweet taste without the associated calories. Paradoxically, non-nutritive sweeteners have been linked to metabolic risks, but the underlying mechanisms are not understood. In this issue of Cell, Suez and colleagues pinpoint changes in the gut microbiome as a mechanism for non-nutritive sweetener-induced glycemic impairments in healthy adults.

Types of diabetes during pregnancy and risk of depression and anxiety in offspring from childhood to young adulthood.

AIMS: To assess maternal pre-existing type 1 diabetes (T1D), type 2 diabetes (T2D), gestational diabetes mellitus (GDM) during pregnancy and risk of depression and anxiety from childhood to young adulthood in offspring. MATERIALS AND METHODS: This birth cohort included singletons born during 1995-2015, followed using electronic medical records through 2020. Cox regression was used to estimate hazard ratio (HR) of depression or anxiety diagnosis during follow-up associated with in-utero exposure to maternal diabetes. RESULTS: Among 439 590 offspring, 29 891 (6.8%) had depression and 51 918 (11.8%) had anxiety. T1D, followed by T2D and GDM requiring antidiabetes medication were associated with risk of depression and anxiety in offspring. Compared with no diabetes during pregnancy, the adjusted HRs (95% confidence interval) of depression in offspring associated with T1D, T2D or GDM requiring medications were 1.44 (1.09-1.91), 1.30 (1.15-1.47) and 1.18 (1.11-1.26) respectively; conversely, HRs were 0.97 (0.82-1.15) for T2D and 0.99 (0.94-1.04) for GDM without medications. The associations with anxiety followed similar patterns. The significant associations were observed for offspring ages 5-12 and >12-18 years and attenuated for 18-25 years. CONCLUSION: These data suggest that the severity of diabetes (T1D vs. T2D requiring medications vs. GDM requiring medications) during pregnancy may increase the vulnerability of offspring for depression or anxiety.

Associations between affect dynamics and eating regulation in daily life: a preliminary ecological momentary assessment study.

Disordered eating behaviors consistently associated with emotion regulation difficulties. However, most studies have focused on affect intensity without considering dynamic affective patterns. We examined these patterns in relation to daily overeating, loss of control eating (LOCE), dietary restraint, and food craving in young adults using ecological momentary assessment (EMA).Adults (N = 24) completed a 10-day EMA protocol during which they reported momentary affect and eating patterns. Generalized linear mixed-models examined each index in relation to eating variable.Higher PA instability (within-person) was associated with higher ratings of binge-eating symptoms (B = 0.15, SE = 0.06, p = 0.007). Lower NA differentiation (within-person) was associated with higher levels of food craving (B = -10.11, SE = 4.74, p = 0.033).Our results support previous findings suggesting that acute fluctuations in PA may increase risk of binge-eating symptoms. Further, inability to differentiate between momentary states of NA was associated with cravings. This study highlights the importance of examining multiple facets of NA and PA in relation to eating regulation.Trial registration: ClinicalTrials.gov identifier: NCT02945475.

Patterns of Objectively Measured Sedentary Time and Emotional Disorder Symptoms Among Youth.

OBJECTIVE: We examined the within-person longitudinal and bidirectional associations between patterns of sedentary time accumulation [alpha (sedentary bout duration/length), sedentary breaks (number of breaks in sedentary bouts)], and symptoms of major depressive disorder and generalized anxiety disorder. METHODS: Children [N = 167, 10.1(0.9) years old, 54.5% female, 59.3% Hispanic, 35.9% overweight/obese at baseline] participated in a 3-year longitudinal study that consisted of assessments of sedentary time, and depressive and anxiety symptoms. At each assessment, participants wore accelerometers and completed the Revised Child Anxiety and Depression Scale. Separate random intercept cross-lagged panel models estimated the within-person longitudinal and bidirectional associations between alpha, sedentary breaks, and symptoms of major depressive disorder and generalized anxiety disorder across chronological age intervals. RESULTS: Having greater than one's own usual depressive symptoms at age 11 was associated with fewer sedentary breaks 1 year later. Having greater than one's own usual generalized anxiety symptoms at age 11 was associated with longer sedentary bouts and fewer sedentary breaks 1 year later. In contrast, having greater than one's own usual sedentary breaks at age 10 was associated with fewer generalized anxiety symptoms 1 year later. All other associations, including at younger ages, were null. CONCLUSION: Deviations from one's usual levels of depressive or anxiety symptoms may be important for how sedentary time is subsequently accumulated. Intraindividual processes appear to be at play, therefore more within-person research is needed. Intervention strategies for promoting a healthier accumulation of sedentary time may consider targeting occasions when depressive and anxiety symptoms are greater than usual.

Glucose variability: A physiological correlate of eating disorder behaviors among individuals with binge-spectrum eating disorders.

OBJECTIVES: Elevated glucose variability may be one mechanism that increases risk for significant psychological and physiological health conditions among individuals with binge-spectrum eating disorders (B-EDs), given the impact of eating disorder (ED) behaviors on blood glucose levels. This study aimed to characterize glucose variability among individuals with B-EDs compared with age-matched, sex-matched, and body mass index-matched controls, and investigate the association between frequency of ED behaviors and glucose variability. METHODS: Participants were 52 individuals with B-EDs and 22 controls who wore continuous glucose monitors to measure blood glucose levels and completed ecological momentary assessment surveys to measure ED behaviors for 1 week. Independent samples t-tests compared individuals with B-EDs and controls and multiple linear regression models examined the association between ED behaviors and glucose variability. RESULTS: Individuals with B-EDs demonstrated numerically higher glucose variability than controls (t = 1.42, p = .08, d = 0.43), although this difference was not statistically significant. When controlling for covariates, frequency of ED behaviors was significantly, positively associated with glucose variability (t = 3.17, p = .003) with medium effect size (f2  = 0.25). Post hoc analyses indicated that binge eating frequency was significantly associated with glucose variability, while episodes of 5+ hours without eating were not. DISCUSSION: Glucose variability among individuals with B-EDs appears to be positively associated with engagement in ED behaviors, particularly binge eating. Glucose variability may be an important mechanism by which adverse health outcomes occur at elevated rates in B-EDs and warrants future study. PUBLIC SIGNIFICANCE: This study suggests that some individuals with binge ED and bulimia nervosa may experience elevated glucose variability, a physiological symptom that is linked to a number of adverse health consequences. The degree of elevation in glucose variability is positive associated with frequency of eating disorder behaviors, especially binge eating.

The effect of body mass index on hippocampal morphology and memory performance in late childhood and adolescence.

Childhood obesity is associated with negative physiological and cognitive health outcomes. The hippocampus is a diverse subcortical structure involved in learned feeding behaviors and energy regulation, and research has shown that the hippocampus is vulnerable to the effects of excess adiposity. Previous studies have demonstrated reduced hippocampal volume in overweight and obese children; however, it is unclear if certain subregions are selectively affected. The purpose of this study was to determine how excess body weight influences regional hippocampal surface morphology and memory performance in a large cross-sectional cohort of 588 children and adolescents between 8.33 and 19.92 years of age using body mass index expressed as a percentage of the 95th percentile cutoff (%BMIp95). We demonstrate %BMIp95 is associated with reduced radial thickness in the superior anterior region of the left hippocampus, and this relationship is predominantly driven by children younger than 14 years. We also found %BMIp95 was associated with worse performance on a spatial episodic memory task and this relationship was partially mediated by the radial thickness of the significant shape cluster. These results demonstrate the differential influence of excess body weight on regional hippocampal structure and hippocampal-dependent behavior in children and adolescents.

Selective morphological and volumetric alterations in the hippocampus of children exposed in utero to gestational diabetes mellitus.

Prior epidemiological studies have found that in utero exposure to gestational diabetes mellitus (GDM) is associated with increased risk for neurodevelopmental disorders. However, brain alterations associated with GDM are not known. The hippocampus is pivotal for cognition and emotional regulation. Therefore, we assessed relationships between in utero exposure to GDM and hippocampal morphology and subfield structure during childhood. One hundred seventeen children aged 7-11 years (57% girls, 57% exposed to GDM), born at Kaiser Permanente Southern California, participated in the BrainChild Study. Maternal GDM status was determined from electronic medical records. Children underwent brain magnetic resonance imaging. Freesurfer 6.0 was used to measure hippocampal and individual hippocampal subfield gray matter volume (mm3 ). Morphological analyses on the hippocampal surface were carried out using shape analysis. GDM-exposed children exhibited reduced radial thickness in a small, spatially-restricted portion of the left inferior body of the hippocampus that corresponds to the CA1 subfield. There was a significant interaction between GDM-exposure and sex on the right hippocampal CA1 subfield. GDM-exposed boys had reduced right CA1 volume compared to unexposed boys, but this association was no longer significant after controlling for age. No significant group differences were observed in girls. Our results suggest that GDM-exposure impacts shape of the left hippocampal CA1 subfield in both boys and girls and may reduce volume of right hippocampal CA1 only in boys. These in-depth findings illuminate the unique properties of the hippocampus impacted by prenatal GDM-exposure and could have important implications for hippocampal-related functions.

Child physical activity as a modifier of the relationship between prenatal exposure to maternal overweight/obesity and neurocognitive outcomes in offspring.

BACKGROUND/OBJECTIVES: With rising obesity rates among pregnant women, more children are exposed in utero to maternal obesity. In prior epidemiological studies, exposure to maternal obesity was associated with lower intelligence quotient (IQ) scores and worse cognitive abilities in offspring. Further studies have shown that offspring exposed to maternal obesity, exhibit differences in the white matter microstructure properties, fractional anisotropy (FA) and mean diffusivity (MD). In contrast, physical activity was shown to improve cognition and white matter microstructure during childhood. We examined if child physical activity levels modify the relationship between prenatal exposure to maternal obesity with IQ and white matter microstructure in offspring. SUBJECTS/METHODS: One hundred children (59% girls) age 7-11 years underwent brain magnetic resonance imaging and IQ testing. Maternal pre-pregnancy BMI was abstracted from electronic medical records. White matter was assessed using diffusion tensor imaging with the measures, global FA, MD. The 3-day physical activity recall was used to measure moderate-to-vigorous physical activity and vigorous physical activity (VPA). Linear regression was used to test for interactions between prenatal exposure to maternal overweight/obesity and child PA levels on child IQ and global FA/MD. RESULTS: The relationship between prenatal exposure to maternal overweight/obesity and child IQ and global FA varied by child VPA levels. Children exposed to mothers with overweight/obesity who engaged in more VPA had higher IQ scores and global FA compared to exposed children who engaged in less VPA. Associations were independent of child age, sex, BMI Z-score and socioeconomic status. Children born to normal-weight mothers did not differ in either IQ or global FA by time in VPA. CONCLUSIONS: Our findings support findings in rodent models and suggest that VPA during childhood modifies the relationship between prenatal exposure to maternal obesity and child IQ and white matter microstructure.

Differential effects of fructose versus glucose on brain and appetitive responses to food cues and decisions for food rewards.

Prior studies suggest that fructose compared with glucose may be a weaker suppressor of appetite, and neuroimaging research shows that food cues trigger greater brain reward responses in a fasted relative to a fed state. We sought to determine the effects of ingesting fructose versus glucose on brain, hormone, and appetitive responses to food cues and food-approach behavior. Twenty-four healthy volunteers underwent two functional magnetic resonance imaging (fMRI) sessions with ingestion of either fructose or glucose in a double-blinded, random-order cross-over design. fMRI was performed while participants viewed images of high-calorie foods and nonfood items using a block design. After each block, participants rated hunger and desire for food. Participants also performed a decision task in which they chose between immediate food rewards and delayed monetary bonuses. Hormones were measured at baseline and 30 and 60 min after drink ingestion. Ingestion of fructose relative to glucose resulted in smaller increases in plasma insulin levels and greater brain reactivity to food cues in the visual cortex (in whole-brain analysis) and left orbital frontal cortex (in region-of-interest analysis). Parallel to the neuroimaging findings, fructose versus glucose led to greater hunger and desire for food and a greater willingness to give up long-term monetary rewards to obtain immediate high-calorie foods. These findings suggest that ingestion of fructose relative to glucose results in greater activation of brain regions involved in attention and reward processing and may promote feeding behavior.

Resting state hypothalamic response to glucose predicts glucose-induced attenuation in the ventral striatal response to food cues.

Feeding behavior is regulated by a complex interaction of central nervous system responses to metabolic signals that reflect nutrient availability and to food cues that trigger appetitive responses. Prior work has shown that the hypothalamus is a key brain area that senses and responds to changes in metabolic signals, and exposure to food cues induces the activation of brain areas involved in reward processing. However, it is not known how the hypothalamic responses to changes in metabolic state are related to reward responses to food cues. This study aimed to understand whether changes in hypothalamic activity in response to glucose-induced metabolic signals are linked to food-cue reactivity within brain areas involved in reward processing. We combined two neuroimaging modalities (Arterial Spin Labeling and Blood Oxygen Level Dependent) to measure glucose-induced changes in hypothalamic cerebral blood flow (CBF) and food-cue task induced changes in brain activity within reward-related regions. Twenty-five participants underwent a MRI session following glucose ingestion and a subset of twenty individuals underwent an additional water session on a separate day as a control condition (drink order randomized). Hunger was assessed before and after drink consumption. We observed that individuals who had a greater reduction in hypothalamic CBF exhibited a greater reduction in left ventral striatum food cue reactivity (Spearman's rho = 0.46, P = 0.048) following glucose vs. water ingestion. These results are the first to use multimodal imaging to demonstrate a link between hypothalamic metabolic signaling and ventral striatal food cue reactivity.

Gestational diabetes mellitus, maternal obesity, and adiposity in offspring.

OBJECTIVE: To determine the effects of maternal gestational diabetes mellitus (GDM) on offspring adiposity in a well-characterized cohort of Mexican American mother-child pairs. STUDY DESIGN: This study included 62 Mexican American mothers and their index offspring. Maternal GDM and normal glucose status during index pregnancy were documented, and mothers were previously matched by age, body mass index (BMI), and parity. Mother-child pairs were recruited when offspring were between the ages of 5 and 16 years. A medical history was collected, and anthropometrics were measured. Main outcome measures were offspring BMI, BMI z-scores, BMI percentiles, and hip and waist circumferences. RESULTS: GDM-exposed offspring (n = 37) had greater measures of BMI (all P ≤ .02) and greater waist and hip circumferences (both P = .002) compared with 25 offspring of non-GDM mothers. Adjustment for offspring age, sex, Tanner stage, birth weight, months of breastfeeding, maternal prepregnancy BMI, and pregnancy weight gain attenuated the differences, but BMI z-score and BMI percentile remained significantly greater in the GDM-exposed group (P < .05). CONCLUSION: Intrauterine exposure to GDM is associated with greater adiposity in Mexican American children, and this relationship is not mediated by maternal obesity. In contrast to previous reports, this study included only Mexican Americans; thus, ethnic variations may influence the contributions of maternal GDM and maternal obesity to offspring adiposity.

Behavioral contributions to the pathogenesis of type 2 diabetes.

Behavioral contributions to the pathogenesis of prediabetes and Type 2 diabetes (T2D) include lifestyle behaviors including dietary intake, exercise, sedentariness, sleep, and stress. The purpose of this paper is to review evidence for the metabolic pathways by which the behavior is linked to T2D. Evidence for interventions, which change each of the lifestyle behaviors, is discussed. The article will close with a brief discussion on how new technologies may provide opportunities to better understand relationships between moment-to-moment fluctuations in behaviors and diabetes pathogenesis, as well as provide opportunities to personalize and adapt interventions to achieve successful behavior change and maintenance of that change. Especially promising are new technologies, which assist in tracking lifestyle behaviors along with clinical and metabolic outcomes.

Perceived stress and associations between physical activity, sedentary time, and interstitial glucose in healthy adolescents.

BACKGROUND: Less moderate to vigorous physical activity (MVPA), more sedentary time (ST), and higher perceived stress are related to type 2 diabetes mellitus (T2DM) occurrence, but observational evidence addressing the interaction of these factors is lacking in youth. This pilot study investigated momentary stress as a moderator in the acute associations of MVPA and ST with subsequent glucose in healthy adolescents. METHODS: Participants (N=15, Mage=13.1±1.0 years, 10 girls, 5 with overweight/obesity) simultaneously wore a continuous glucose monitor (CGM), thigh-mounted accelerometer, and reported momentary stress via random ecological momentary assessments (EMA; Time T) for 7-14 days. MVPA and ST (min) were calculated for 60- and 120-minute time windows before each EMA prompt (Time T-1). Mean CGM-measured interstitial glucose (mg/dL) was calculated after each prompt (Mmin=120.0±25.4; Time T+1). Multilevel models assessed whether within-subject MVPA and ST (Time T-1) predicted mean glucose (Time T+1), with momentary stress as a moderator (Time T). RESULTS: There were 513 time-matched EMA reports of stress, accelerometer, and CGM data. Momentary stress moderated the effects of MVPA 60 (ß=-0.22, p=.001) and 120 min (ß=-0.08, p=.02) before the prompt on subsequent glucose levels. When youth spent more time in MVPA than their average and when momentary stress was higher than their average, subsequent glucose was lower. Stress did not moderate associations of ST with glucose (p>.05). CONCLUSIONS: Higher momentary stress may interact with higher MVPA to lower subsequent glucose in youth. Accelerometers, EMA, and CGMs can be integrated in future studies to further understand these associations in free-living environments.

Influence of insulin sensitivity on food cue evoked functional brain connectivity in children.

Objective: Insulin resistance during childhood is a risk factor for developing type 2 diabetes and other health problems later in life. Studies in adults have shown that insulin resistance affects regional and network activity in the brain which are vital for behavior, e.g. ingestion and metabolic control. To date, no study has investigated whether brain responses to food cues in children are associated with peripheral insulin sensitivity. Methods: We included 53 children (36 girls) between the age of 7-11 years, who underwent an oral Glucose Tolerance Test (oGTT) to estimate peripheral insulin sensitivity (ISI). Brain responses were measured using functional magnetic resonance imaging (fMRI) before and after glucose ingestion. We compared food-cue task-based activity and functional connectivity (FC) between children with low and high ISI, adjusted for age and BMIz. Results: Independent of prandial state (i.e., glucose ingestion), children with lower ISI showed higher FC between the anterior insula and caudate and lower FC between the posterior insula and mid temporal cortex than children with higher ISI. Sex differences were found based on prandial state and peripheral insulin sensitivity in the insular FC. No differences were found on whole-brain food-cue reactivity. Conclusions: Children with low peripheral insulin sensitivity showed differences in food cue evoked response particularly in insula functional connectivity. These differences might influence eating behavior and future risk of developing diabetes.

Maternal obesity and diabetes during pregnancy and early autism screening score at well-child visits in standard clinical practice.

LAY ABSTRACT: Early intervention and treatment can help reduce disability in children diagnosed with autism spectrum disorder. Screening for autism spectrum disorder in young children identifies those at increased likelihood of diagnosis who may need further support. Previous research has reported that exposure to maternal obesity and diabetes during pregnancy is associated with higher likelihood of autism spectrum disorder diagnosis in children. However, little is known about whether these maternal conditions are associated with how very young children score on autism spectrum disorder screening tools. This study examined associations between exposure to maternal obesity and diabetes during pregnancy and offspring scores on the Quantitative Checklist for Autism in Toddlers, an autism spectrum disorder screening questionnaire administered between 18-24 months at well-child visits. A higher score on the Quantitative Checklist for Autism in Toddlers suggests a higher likelihood of autism spectrum disorder; children with scores 3 or greater are referred to developmental pediatricians for evaluation. Our study found that children of mothers with obesity or diabetes during pregnancy had higher scores than children whose mothers did not have these conditions. Associations with maternal obesity and gestational diabetes diagnosed at or before 26 weeks of pregnancy were also present in children who did not have later autism spectrum disorder diagnoses, suggesting that exposure to these conditions during early pregnancy may be associated with a broad range of social and behavioral abilities. Identifying associations between maternal health conditions and early Quantitative Checklist for Autism in Toddlers screening scores could influence future screening and provision of support for children of mothers with these conditions.

Interventions to preserve beta-cell function in the management and prevention of type 2 diabetes.

The International Diabetes Federation estimates that there are currently 336 million people worldwide who have type 2 diabetes (T2DM), and the global prevalence of diabetes has more than doubled since 1980. The rapid rise in rates of T2DM echoes a similar rise in rates of obesity, which causes insulin resistance and places an increased insulin secretory demand on pancreatic ß cells. While diabetes is diagnosed clinically by elevated plasma glucose levels, loss of ß-cell function is progressive over time and ß-cell dysfunction is far advanced by the time diabetes is diagnosed. Methods for preserving or restoring ß-cell function are important for the prevention and treatment of T2DM. Interventions that reduce body fat or that change fat biology provide the best evidence for slowing or arresting the deterioration of ß-cell function that causes T2DM. These interventions should form the basis of interventions to prevent and treat T2DM, particularly early in its course.

Effects of fructose vs glucose on regional cerebral blood flow in brain regions involved with appetite and reward pathways.

IMPORTANCE: Increases in fructose consumption have paralleled the increasing prevalence of obesity, and high-fructose diets are thought to promote weight gain and insulin resistance. Fructose ingestion produces smaller increases in circulating satiety hormones compared with glucose ingestion, and central administration of fructose provokes feeding in rodents, whereas centrally administered glucose promotes satiety. OBJECTIVE: To study neurophysiological factors that might underlie associations between fructose consumption and weight gain. DESIGN, SETTING, AND PARTICIPANTS: Twenty healthy adult volunteers underwent 2 magnetic resonance imaging sessions at Yale University in conjunction with fructose or glucose drink ingestion in a blinded, random-order, crossover design. MAIN OUTCOME MEASURES: Relative changes in hypothalamic regional cerebral blood flow (CBF) after glucose or fructose ingestion. Secondary outcomes included whole-brain analyses to explore regional CBF changes, functional connectivity analysis to investigate correlations between the hypothalamus and other brain region responses, and hormone responses to fructose and glucose ingestion. RESULTS: There was a significantly greater reduction in hypothalamic CBF after glucose vs fructose ingestion (-5.45 vs 2.84 mL/g per minute, respectively; mean difference, 8.3 mL/g per minute [95% CI of mean difference, 1.87-14.70]; P = .01). Glucose ingestion (compared with baseline) increased functional connectivity between the hypothalamus and the thalamus and striatum. Fructose increased connectivity between the hypothalamus and thalamus but not the striatum. Regional CBF within the hypothalamus, thalamus, insula, anterior cingulate, and striatum (appetite and reward regions) was reduced after glucose ingestion compared with baseline (P < .05 significance threshold, family-wise error [FWE] whole-brain corrected). In contrast, fructose reduced regional CBF in the thalamus, hippocampus, posterior cingulate cortex, fusiform, and visual cortex (P < .05 significance threshold, FWE whole-brain corrected). In whole-brain voxel-level analyses, there were no significant differences between direct comparisons of fructose vs glucose sessions following correction for multiple comparisons. Fructose vs glucose ingestion resulted in lower peak levels of serum glucose (mean difference, 41.0 mg/dL [95% CI, 27.7-54.5]; P < .001), insulin (mean difference, 49.6 µU/mL [95% CI, 38.2-61.1]; P < .001), and glucagon-like polypeptide 1 (mean difference, 2.1 pmol/L [95% CI, 0.9-3.2]; P = .01). CONCLUSION AND RELEVANCE: In a series of exploratory analyses, consumption of fructose compared with glucose resulted in a distinct pattern of regional CBF and a smaller increase in systemic glucose, insulin, and glucagon-like polypeptide 1 levels.

Prenatal Exposure to Gestational Diabetes Mellitus is Associated with Mental Health Outcomes and Physical Activity has a Modifying Role.

Background: Studies suggest a link between prenatal gestational diabetes mellitus (GDM) exposure and poor mental health outcomes. We examined associations between prenatal GDM exposure and depressive and anxiety symptoms in children and assessed physical activity as a potential modifier of these associations. Method: Seventy children (AgeM(SD): 12(2.0), 56% GDM, 59% female) and their parents completed surveys: Center for Epidemiological Studies Depression Scale for Children (CES-DC), State-Trait Anxiety Inventory for Children (STAIC), Child Behavior Checklist (CBCL), and 3-day physical activity recall (3DPAR). Associations between mental health measures with GDM exposure and interactions between GDM exposure and child moderate-to-vigorous physical activity (MVPA) were assessed using regression. Results: GDM-exposed children had higher anxiety (p = 0.03) and internalizing symptoms (CBCL) (p = 0.04) than unexposed children. There was an interaction between GDM exposure and child MVPA on anxiety (p = 0.02), internalizing (p = 0.04) and externalizing symptoms (p = 0.004). In the low MVPA group, GDM exposed children had more depressive (p = 0.03), anxiety (p = 0.003), and internalizing symptoms (p = 0.03) than unexposed children. In the high MVPA group, there were no group differences except with externalizing symptoms (p = 0.04). Conclusion: Prenatal GDM is associated with higher anxiety and internalizing symptoms in children. Child MVPA modified the relationship between GDM exposure and mental health outcomes suggesting that physical activity during childhood could mitigate the negative mental health outcomes associated with prenatal GDM exposure.

Associations among prenatal exposure to gestational diabetes mellitus, brain structure, and child adiposity markers.

OBJECTIVE: The aim of this study was to investigate the mediating role of child brain structure in the relationship between prenatal gestational diabetes mellitus (GDM) exposure and child adiposity. METHODS: This was a cross-sectional study of 9- to 10-year-old participants and siblings across the US. Data were obtained from the baseline assessment of the Adolescent Brain Cognitive Development (ABCD) Study®. Brain structure was evaluated by magnetic resonance imaging. GDM exposure was self-reported, and discordance for GDM exposure within biological siblings was identified. Mixed effects and mediation models were used to examine associations among prenatal GDM exposure, brain structure, and adiposity markers with sociodemographic covariates. RESULTS: The sample included 8521 children (7% GDM-exposed), among whom there were 28 sibling pairs discordant for GDM exposure. Across the entire study sample, prenatal exposure to GDM was associated with lower global and regional cortical gray matter volume (GMV) in the bilateral rostral middle frontal gyrus and superior temporal gyrus. GDM-exposed siblings also demonstrated lower global cortical GMV than unexposed siblings. Global cortical GMV partially mediated the associations between prenatal GDM exposure and child adiposity markers. CONCLUSIONS: The results identify brain markers of prenatal GDM exposure and suggest that low cortical GMV may explain increased obesity risk for offspring prenatally exposed to GDM.