The resolution of type 2 diabetes after Roux-en-Y gastric bypass (RYGB) attests to the important role of the gastrointestinal tract in glucose homeostasis. Previous studies in RYGB-treated rats have ...shown that the Roux limb displays hyperplasia and hypertrophy. Here, we report that the Roux limb of RYGB-treated rats exhibits reprogramming of intestinal glucose metabolism to meet its increased bioenergetic demands; glucose transporter-1 is up-regulated, basolateral glucose uptake is enhanced, aerobic glycolysis is augmented, and glucose is directed toward metabolic pathways that support tissue growth. We show that reprogramming of intestinal glucose metabolism is triggered by the exposure of the Roux limb to undigested nutrients. We demonstrate by positron emission tomography—computed tomography scanning and biodistribution analysis using 2-deoxy-2-18Ffluoro-D-glucose that reprogramming of intestinal glucose metabolism renders the intestine a major tissue for glucose disposal, contributing to the improvement in glycemic control after RYGB.
Background
While Roux-en-Y gastric bypass (RYGB) is one of the most effective and durable treatment options for obesity and its comorbidities, it is complicated by long-term weight regain in over 20% ...of patients.
Aims
We sought to determine the metabolite signatures of serum samples of patients with weight regain (RYGB-WR) after RYGB and features distinguishing these patients from patients with sustained weight loss (RYGB-SWL).
Methods
We prospectively analyzed serum samples from 21 RYGB-WR patients, 14 RYGB-SWL patients, and 11 unoperated controls. The main outcome measure was their serum metabolite profile.
Results
Weight regain after RYGB was associated with a unique serum metabolomic fingerprint. Most of the statistically different metabolites were involved in amino acid metabolism, one-carbon metabolism, and related nucleotide metabolism. A principal component analysis identified groups of metabolites that correlate with weight regain. Specifically, weight regain was associated with lower serum levels of metabolites related to the serine, glycine and threonine pathway, phenylalanine metabolism, tricyclic acid cycle, alanine and glutamate metabolism, and higher levels of other amino acids.
Conclusions
Weight regain after RYGB is associated with unique serum metabolite signatures. Metabolite profiling may eventually help us to identify markers that could differentiate the patients who will regain weight versus those who will likely sustain weight loss.
Objectives:
Pregnant people infected with SARS-CoV-2, the virus that causes COVID-19, are at increased risk for severe illness and death compared with nonpregnant people. However, population-based ...information comparing characteristics of people with and without laboratory-confirmed SARS-CoV-2 infection during pregnancy is limited. We compared the characteristics of people with and without SARS-CoV-2 infection during pregnancy in Massachusetts.
Methods:
We compared maternal demographic characteristics, pre-pregnancy conditions, and pregnancy complications of people with and without SARS-CoV-2 infection during pregnancy with completed pregnancies resulting in a live birth in Massachusetts during March 1, 2020–March 31, 2021. We tested for significant differences in the distribution of characteristics of pregnant people by SARS-CoV-2 infection status overall and stratified by race and ethnicity. We used modified Poisson regression analyses to examine the association between race and ethnicity and SARS-CoV-2 infection during pregnancy.
Results:
Of 69 960 completed pregnancies identified during the study period, 3119 (4.5%) had laboratory-confirmed SARS-CoV-2 infection during pregnancy. Risk for SARS-CoV-2 infection was higher among Hispanic (adjusted risk ratio aRR = 2.3; 95% CI, 2.1-2.6) and non-Hispanic Black (aRR = 1.9; 95% CI, 1.7-2.1) pregnant people compared with non-Hispanic White pregnant people.
Conclusions:
This study demonstrates the disproportionate impact of SARS-CoV-2 infection on Hispanic and non-Hispanic Black pregnant people in Massachusetts, which may widen existent inequities in maternal morbidity and mortality. Future research is needed to elucidate the structural factors leading to these inequities.
Oxidative stress and redox imbalance adversely affect embryonic development. We developed two oxidative balance scores (OBS) that include dietary and nondietary exposures. We hypothesized that higher ...scores (i.e., lower oxidative stress) would be associated with lower risk of neural tube defects, orofacial clefts, conotruncal heart defects, and limb deficiencies. We used data from the National Birth Defects Prevention Study to create a dietary OBS based on intake of 13 nutrients and an overall OBS that included the 13 nutrients and eight additional nondietary factors related to oxidative balance (e.g., smoking). We used logistic regression to examine odds ratios associated with having low or high scores (i.e., <10th or >90th percentiles). Continuous models indicated reduced odds associated with high versus low scores (i.e., comparing odds at the 90th versus 10th percentile values of the distribution) on the overall OBS for cleft lip with or without cleft palate adjusted odds ratio (aOR) 0.72, 95% confidence interval (CI) 0.63–0.82, longitudinal limb deficiency (aOR 0.73, CI 0.54–0.99), and transverse limb deficiency (aOR 0.74, CI 0.58–0.95); increased odds for anencephaly (aOR 1.40, CI 1.07–1.84); and primarily nonsignificant associations with conotruncal heart defects. Results for the dietary OBS were similar. This study provides some evidence that oxidative stress contributes to congenital anomalies related to neural crest cell development.
Although the prevalence of obesity has increased dramatically throughout the world during the last 25 yr, its long-term control remains poor. Currently, only gastrointestinal weight loss surgery, ...especially Roux-en-Y gastric bypass (RYGB), is associated with substantial and sustained weight loss and resolution or significant improvement of diabetes mellitus and other metabolic obesity-induced complications. Clinical observations and recent studies have suggested that RYGB induces its effects by changing the physiology of weight regulation. Understanding the underlying mechanisms of these profound and sustainable effects could facilitate the development of novel and less invasive treatments against obesity and its complications. To study the physiological mechanisms of RYGB, we have developed a mouse RYGB model that replicates the human operation. The aims of this study were to develop a roadmap for assessing energy expenditure (EE) in animal models of weight loss surgery and to examine the effects of RYGB on EE. We first measured EE by indirect calorimetry in groups of animals that underwent RYGB or a sham operation. Calorimetry data were analyzed using three different methods: normalization by total body mass, allometric scaling, and analysis of covariance modeling. RYGB in mice induced a significant increase in EE that was independent of the method used. An energy balance analysis was then performed, which also confirmed that RYGB-treated animals have higher energy maintenance needs. Finally, we determined the EE components that account for the observed increase in EE, and we found that resting EE and postprandial thermogenesis are the major contributors to this increase.
Background
SARS‐CoV‐2 infection during pregnancy has been linked to preterm birth, but this association is not well understood.
Objectives
To examine the association between SARS‐CoV‐2 infection and ...spontaneous and provider‐initiated preterm birth (PTB), and how timing of infection, and race/ethnicity as a marker of structural inequality, may modify this association.
Methods
We conducted a retrospective cohort study among pregnant people who delivered singleton, liveborn infants (22–44 weeks gestation) from 1 March 2020 to 31 March 2021 (n = 68,288). We used Cox proportional hazards models to compare the hazard of PTB between pregnant people with and without laboratory‐confirmed SARS‐CoV‐2 infection during pregnancy. We evaluated this association according to the trimester of infection, timing from infection to birth, and timing of PTB. We also examined the joint associations of SARS‐CoV‐2 infection and race/ethnicity with PTB using the relative excess risk due to interaction (RERI).
Results
Positive SARS‐CoV‐2 tests were identified for 2195 pregnant people (3.2%). The prevalence of PTB was 7.2% (3.8% spontaneous, 3.6% provider‐initiated). SARS‐CoV‐2 infection during pregnancy was associated with an increased risk of PTB overall (adjusted hazard ratio HR 1.53, 95% confidence interval CI 1.34, 1.74), and provider‐initiated PTB (HR 1.79, 95% CI 1.50, 2.12) but not spontaneous PTB (HR 1.09, 95% CI 0.89, 1.36). Second trimester infections were associated with an increased risk of provider‐initiated PTB, and third trimester infections were associated with an increased risk of both PTB subtypes. A joint inverse association between White non‐Hispanic race/ethnicity and SARS‐CoV‐2 infection and spontaneous PTB (HR 0.56, 95% CI 0.34, 0.94; RERI −0.6, 95% CI −1.0, −0.2) was also observed.
Conclusions
SARS‐CoV‐2 infections were primarily associated with an increased risk for provider‐initiated PTB in this study. These findings highlight the importance of promoting infection‐prevention strategies among pregnant people.
To describe trends in delayed diagnosis of critical congenital heart defects (CCHDs) with prenatal and postnatal screening advances.
We evaluated a retrospective cohort of live births with CCHD ...delivered between 2004 and 2018 from a statewide, population-based birth defects surveillance system in Massachusetts. Demographic information were obtained from vital records. We estimated timely (prenatal or birth/transfer hospital) and delayed diagnosis (after discharge) proportions by year and time periods coinciding with the transition to mandatory pulse oximetry in 2015.
We identified 1524 eligible CCHD cases among 1 087 027 live births. By 2018, 92% of cases received a timely diagnosis, most prenatally. From 2004 to 2018, prenatal diagnosis increased from 46% to 76% of cases, while hospital diagnosis decreased from 38% to 17%, and delayed diagnosis declined from 16% to 7%. These trends were consistent across all characteristics evaluated. Among cases without a prenatal diagnosis, the proportion with delayed diagnosis did not change over time, even after implementation of mandatory pulse oximetry screening. Prenatal detection increased the most among severe cases (treated or died in first month of life). Well-appearing newborns without prenatal diagnosis made up 79% of delayed diagnosis cases by 2015-2018. Delayed diagnosis was most common for coarctation.
While prenatal diagnosis of CCHD increased dramatically, there was no reduction in delayed diagnosis among postnatally diagnosed infants, even after pulse oximetry screening became mandatory. Pulse oximetry may not reduce delayed diagnosis in settings with high prenatal detection, and other strategies are needed to ensure timely diagnosis of well-appearing newborns.
Objectives: In 2019, the Council of State and Territorial Epidemiologists ratified a multitiered standardized surveillance case definition (SSCD) for neonatal abstinence syndrome (NAS) to minimize ...variability in definitions across states. This evaluation of the tier 1 NAS SSCD aimed to identify common challenges and opportunities for enhancement to support consistent implementation of the definition. Methods: This mixed-methods analysis consisted of 3 virtual focus groups in March 2021 with site principal investigators, medical record abstractors, and data analysts (1 focus group each) from 4 jurisdictions piloting the tier 1 NAS SSCD. We analyzed focus group transcripts to create a codebook. We collected written reports in February 2022 from the 4 jurisdictions, conducted thematic analysis of focus group transcripts and written reports to identify themes, and collected surveillance data on infants identified with NAS born from January 2020 through December 2021 from the pilot sites. We analyzed surveillance data to further inform identified themes. We examined agreement among tier 1 classifications assigned independently by each pilot site and the Centers for Disease Control and Prevention to cases of NAS. Results: Three major themes emerged in the data: challenges abstracting data on withdrawal signs from the medical record, difficulty determining the time frame of prenatal substance exposure, and challenges assigning case classifications. In a comparison of tier 1 classifications assigned by the Centers for Disease Control and Prevention and the sites, 82.1% of cases in the dataset were concordant. Conclusions: We identified several opportunities to modify the SSCD to promote consistency and ease implementation across jurisdictions. Promoting consistent implementation supports comparability of NAS incidence estimates across jurisdictions, evaluation of prevention efforts, and allocation of resources to support families.
•Consumption of a high glycemic index diet during the preconception period does not appear to increase the risk for delivering a large-for-gestational-age infant (LGA).•Consumption of a high glycemic ...index diet during the preconception period does not appear to appreciably strengthen the association between prepregnancy body mass index and LGA.•Consumption of a high glycemic index diet during the preconception period does not appear to influence the association between prepregnancy body mass index and LGA.
Diets with a high glycemic index (GI) leading to elevated postprandial glucose levels and hyperinsulinemia during pregnancy have been inconsistently linked to an increased risk for large-for-gestational-age (LGA) births. The effects of prepregnancy dietary GI on LGA risk are, to our knowledge, unknown. We examined the association of prepregnancy dietary GI with LGA births and joint associations of GI and maternal overweight/obesity and infant sex with LGA births among 10 188 infants born without congenital anomalies from 1997 to 2011, using data from the National Birth Defects Prevention Study (NBDPS). The aim of this study was to investigate this association among infants without major congenital anomalies (controls) who participated in the NBDPS and to evaluate how prepregnancy BMI and infant sex may modify this association on the additive scale.
Dietary intake was ascertained using a 58-item food frequency questionnaire. We dichotomized dietary GI into high and low categories using spline regression models. Infants with a birth weight at or above the 90th percentile for gestational age and sex, according to a U.S. population reference, were considered LGA. We used logistic regression to obtain odds ratios (ORs) and 95% confidence intervals (CIs).
Of the infants, 859 (9%) had a high dietary GI (cut-point: 59), and 1244 infants (12%) were born LGA. Unadjusted analysis suggested an inverse association between high dietary GI and LGA (OR, 0.79; 95% CI, 0.62–0.99). No association was observed in multivariable models when comparing high dietary GI intake between LGA births and all other births (OR, 0.94; 95% CI, 0.74–1.20) or when excluding small-for-gestational-age (SGA) births (OR, 0.94; 95% CI, 0.73–1.19). No joint associations with maternal overweight/obesity or infant sex were observed.
High prepregnancy maternal GI was not associated with LGA births independently of or jointly with other factors.
The effectiveness of Roux-en-Y gastric bypass (RYGB) against obesity and its comorbidities has generated excitement about developing new, less invasive treatments that use the same molecular ...mechanisms. Although controversial, RYGB-induced improvement of metabolic function may not depend entirely upon weight loss. To elucidate the differences between RYGB and dieting, we studied several individual organ molecular responses and generated an integrative, interorgan view of organismal physiology. We also compared murine and human molecular signatures. We show that, although dieting and RYGB can bring about the same degree of weight loss, post-RYGB physiology is very different. RYGB induces distinct, organ-specific adaptations in a temporal pattern that is characterized by energetically demanding processes, which may be coordinated by HIF1a activation and the systemic repression of growth hormone receptor signaling. Many of these responses are conserved in rodents and humans and may contribute to the remarkable ability of surgery to induce and sustain metabolic improvement.
Display omitted
•Compared with dieting, RYGB leads to sustained weight loss and metabolic improvement•RYGB dynamically modulates organ-specific signaling and metabolic pathways•Many of these effects are conserved in rodents and humans•RYGB induces a new metabolic state, which may explain its remarkable effectiveness
Using an integrative, interorgan view of organismal physiology, Ben-Zvi et al. compared RYGB gastric bypass and dieting in mouse and humans. Although dieting and RYGB can bring about the same degree of weight loss, the molecular signature of surgery highlights an essential role for metabolic regulators and the circadian clock.
PDF
