A Pilot Study Using Continuous Glucose Monitoring among Patients with a Low 1-Hour Glucose Challenge Test Result versus Controls to Detect Maternal Hypoglycemia.

OBJECTIVE: A low 1-hour glucose challenge test (GCT) result (<10th percentile for population) has been associated with neonatal morbidity, including small-for-gestational-age birth weight, and it is hypothesized that underlying maternal hypoglycemia may contribute to this neonatal morbidity. We sought to assess whether eligible patients would undergo continuous glucose monitoring to allow comparison of maternal hypoglycemia between those with a low GCT result versus controls. STUDY DESIGN: This exploratory study enrolled patients who completed a GCT between 24 and 30 weeks' gestation from June to September 2022. English- or Spanish-speaking participants aged ≥18 years wore a blinded continuous glucose monitor (CGM) for 10 days. There were 10 participants each in the low GCT (<82 mg/dL) and normal GCT group. Proportions were calculated to determine recruitment rates and describe the low versus normal glycemic groups across clinical and sociodemographic characteristics. Maternal hypoglycemia, defined using various proposed thresholds, was analyzed as continuous data (time duration) with Student's t-tests and categorical data (number of episodes) with chi-square tests and bivariate analyses were performed comparing participants with a low versus normal GCT. Primary outcome measures were recruitment, enrollment, and adherence rates, and overall glycemic values for each group. RESULTS: Of 64 eligible patients, 58 (91%) were approached, and of them, 20 (35%) were enrolled. All 20 participants had CGM data to review with 100% adherence. Average glucose values were similar between participants in the low GCT and normal GCT groups (111.7 ± 18.0 vs. 111.6 ± 11.7 mg/dL, p = 0.99), and participants with a low GCT value did not demonstrate more hypoglycemia than those with a normal GCT value across five proposed thresholds on CGM analysis. CONCLUSION: In this pilot study, participants wore blinded CGMs to collect glycemic data, and those with a low GCT result did not experience more hypoglycemia than those with a normal GCT on CGM analysis. KEY POINTS: · Study participants wore continuous glucose monitors in blinded mode to gather glycemic data with 100% adherence.. · Participants with a low GCT result (<82 mg/dL) as compared with those with a normal GCT result were not more likely to demonstrate maternal hypoglycemia using several thresholds on CGM analysis.. · In our cohort, there were few participants in either glycemic group who reported food insecurity or lived in a food desert..

Brain dopamine responses to ultra-processed milkshakes are highly variable and not significantly related to adiposity in humans.

Ultra-processed foods high in fat and sugar may be addictive, in part, due to their purported ability to induce an exaggerated postingestive brain dopamine response akin to drugs of abuse. Using standard [11C]raclopride positron emission tomography (PET) displacement methods used to measure brain dopamine responses to addictive drugs, we measured postingestive striatal dopamine responses to an ultra-processed milkshake high in fat and sugar in 50 young, healthy adults over a wide body mass index range (BMI 20-45 kg/m2). Surprisingly, milkshake consumption did not result in significant postingestive dopamine response in the striatum (p=0.62) nor any striatal subregion (p>0.33) and the highly variable interindividual responses were not significantly related to adiposity (BMI: r=0.076, p=0.51; %body fat: r=0.16, p=0.28). Thus, postingestive striatal dopamine responses to an ultra-processed milkshake were likely substantially smaller than many addictive drugs and below the limits of detection using standard PET methods.

The association between a low 50-gram, 1-hour glucose challenge test value and neonatal morbidity.

OBJECTIVE: To evaluate the association between a low 50-gram, 1-hour glucose challenge test (GCT) value and adverse maternal and neonatal outcomes among patients receiving care at a single center tertiary care academic hospital. METHODS: We performed a retrospective cohort study of pregnant patients with a documented result of a 50-gram, 1-hour GCT performed ≥24 weeks 0 days gestation at a single tertiary care academic hospital from 2013-2021. Patients with a low GCT value, defined as cohort specific ≤10th percentile (<82 mg/dL), were compared to patients with a GCT value ≥82 mg/dL who were not diagnosed with gestational diabetes (GDM) to examine adverse maternal and neonatal outcomes. Additionally, these comparisons were repeated across patients with low GCT (<82 mg/dL), those with a GCT ≥82 mg/dL without diagnosis of GDM (heretofore referred to as normal glycemic screening) and patients diagnosed with GDM. Our primary outcome was a composite neonatal morbidity variable, inclusive of stillbirth, neonatal death, neonatal hypoglycemia with neonatal intensive care unit (NICU) admission, neonatal hyperbilirubinemia with NICU admission, respiratory distress with NICU admission, and/or small for gestational age (SGA). Multivariable logistic regression modeling was used to examine the association of low GCT value and the composite neonatal morbidity outcome, compared to those with the normal glycemic screening. RESULTS: Of 36,342 eligible patients, 3,789 (10.4%) had a low GCT value of <82 mg/dL, 30,729 (84.6%) had a GCT value ≥82 mg/dL and were not diagnosed with GDM, and 1,824 (5.0%) had a diagnosis of GDM. Patients with a low GCT value were significantly less likely to be diagnosed with hypertensive disorder of pregnancy (HDP) (12.4% vs 16.3%, p < .01), undergo cesarean delivery (22.8% vs 29.9%, p < .01), or experience postpartum hemorrhage (7.8% vs 9.4%, p < .01) as compared to patients with normal glycemic screening. Compared to newborns whose mothers had normal glycemic screening, newborns of mothers with a low GCT value were significantly more likely to experience the composite morbidity outcome (OR 1.17; 95% CI 1.08-1.27); this persisted after adjusting for potential confounders (aOR 1.18; 95% CI 1.09-1.29). CONCLUSION: A low maternal GCT value after 24 weeks gestation is significantly associated with an increased risk of morbidity in the newborn, driven by higher rates of SGA. Patients with a low GCT value may have underlying maternal hypoglycemia or other glycemic dysregulation affecting fetal development and may benefit from enhanced antenatal surveillance.

Striatal dopamine tone is positively associated with body mass index in humans as determined by PET using dual dopamine type-2 receptor antagonist tracers.

The relationship between adiposity and dopamine type-2 receptor binding potential (D2BP) in the human brain has been repeatedly studied for >20 years with highly discrepant results, likely due to variable methodologies and differing study populations. We conducted a controlled inpatient feeding study to measure D2BP in the striatum using positron emission tomography with both [18F]fallypride and [11C]raclopride in pseudo-random order in 54 young adults with a wide range of body mass index (BMI 20-44 kg/m2). Within-subject D2BP measurements using the two tracers were moderately correlated (r=0.47, p<0.001). D2BP was negatively correlated with BMI as measured by [11C]raclopride (r= -0.51; p<0.0001) but not [18F]fallypride (r=-0.01; p=0.92) and these correlation coefficients were significantly different from each other (p<0.001). Given that [18F]fallypride has greater binding affinity to dopamine type-2 receptors than [11C]raclopride, which is more easily displaced by endogenous dopamine, our results suggest that adiposity is positively associated with increased striatal dopamine tone.

Effect of a plant-based, low-fat diet versus an animal-based, ketogenic diet on ad libitum energy intake.

The carbohydrate-insulin model of obesity posits that high-carbohydrate diets lead to excess insulin secretion, thereby promoting fat accumulation and increasing energy intake. Thus, low-carbohydrate diets are predicted to reduce ad libitum energy intake as compared to low-fat, high-carbohydrate diets. To test this hypothesis, 20 adults aged 29.9 ± 1.4 (mean ± s.e.m.) years with body mass index of 27.8 ± 1.3 kg m-2 were admitted as inpatients to the National Institutes of Health Clinical Center and randomized to consume ad libitum either a minimally processed, plant-based, low-fat diet (10.3% fat, 75.2% carbohydrate) with high glycemic load (85 g 1,000 kcal-1) or a minimally processed, animal-based, ketogenic, low-carbohydrate diet (75.8% fat, 10.0% carbohydrate) with low glycemic load (6 g 1,000 kcal-1) for 2 weeks followed immediately by the alternate diet for 2 weeks. One participant withdrew due to hypoglycemia during the low-carbohydrate diet. The primary outcomes compared mean daily ad libitum energy intake between each 2-week diet period as well as between the final week of each diet. We found that the low-fat diet led to 689 ± 73 kcal d-1 less energy intake than the low-carbohydrate diet over 2 weeks (P < 0.0001) and 544 ± 68 kcal d-1 less over the final week (P < 0.0001). Therefore, the predictions of the carbohydrate-insulin model were inconsistent with our observations. This study was registered on ClinicalTrials.gov as NCT03878108 .