Faculty Bibliography

Endocrine-disrupting chemicals (EDCs) are a prime concern for the environment and health globally. Research shows that in developing countries such as India both the environment and human populations are severely exposed to EDCs and consequently experience rising incidents of adverse health effects such as diabetes and cancers. In this paper, we discuss the current EDC management approach in India, critically assess its limitations, and describe opportunities for potential improvements. Foremost, current EDC management actions and interventions in India are fragmented and outdated, and far behind the modern and comprehensive approaches adopted in the European Union and other developed countries. Strong and well-planned actions are required on various fronts of science, policy, commerce, and public engagement. These actions include the adoption of a dedicated and modern regulatory framework for managing EDCs, enhancing capacity and infrastructure for EDC monitoring in the environment and human population, employing public-private partnership programs for not only managing EDCs but also in the sectors that indirectly contribute toward the mismanagement of EDCs in the country, and raising awareness on EDCs and promoting health-preserving consumption habits among the public. As India hosts a large proportion of the global human population and biodiversity, the success or failure of its actions will substantially affect the direction of global efforts to manage EDCs and set an example for other developing countries.

OBJECTIVE:, suggesting that elevated suPAR levels may reflect a heightened inflammatory response in preeclamptic pregnancies rather than serving as a pre-clinical indicator. No data currently exist on the trajectory of suPAR across pregnancy. In the present study, we investigated if and how plasma suPAR levels change across gestation and examined whether this change and the levels in each trimester varied between women with and without HDP. STUDY DESIGN/METHODS:Participants included pregnant individuals enrolled in the [study name removed for blinding], a prospective birth cohort designed to study an array of exposures and conditions relevant to maternal and child health. Maternal blood was collected at up to three time points during pregnancy and plasma suPAR levels were analyzed by enzyme-linked immunosorbent assay. Information on maternal HDP was abstracted from electronic medical records. Study participants with suPAR data in any trimester and information about HDP were eligible for inclusion (n=393); 64 non-HDP participants who had chronic hypertension (n=5), gestational diabetes mellitus (n=55), lupus (n=1), type 1 diabetes (n=1) or type 2 diabetes (n=2) were excluded, resulting in a final analytic sample of 329. The study was approved by the Institutional Review Board of the [institution removed for blinding] and all participants provided written informed consent. We first regressed suPAR levels on gestational age at the time of sample collection to assess change over the course of pregnancy. We did this for the sample overall and stratified by HDP status. Among the subset of participants with repeated measures, we used paired Wilcoxon signed-rank tests to assess the within-person change in suPAR across trimesters in both groups. Finally, we used Wilcoxon signed-rank tests to assess whether suPAR levels in each trimester and averaged over pregnancy were different among participants with and without HDP. RESULTS:and ranged from 16.8-50.1; 44% of the sample was overweight or obese defined by a BMI ≥ 25. The majority had at least a high school degree (90.1%) and reported never smoking cigarettes (92.9%). Participants with HDP (n=44) were older and had higher BMI; other participant characteristics did not significantly vary by HDP status. suPAR levels did not significantly differ between those with and without HDP at any gestational timepoint (Table 1), although the association was marginal when considering the third trimester such that those with HDP had higher suPAR levels (2.43 ng/mL vs. 2.12 ng/mL, p=0.11). In the sample overall, suPAR levels decreased by 1.1% per week of advancing gestation (p-value< 0.001); however, when stratified by HDP status, suPAR levels only significantly decreased among those without HDP (1.2% per week, p<0.001), while remaining more stable among the cases (0.8% per week, p=0.17) (Figure 1). This finding was also apparent when examining the subset of participants with repeated measures. Among those with paired samples that did not have HDP, the median suPAR level in early gestation (2.79 ng/mL) was significantly higher than late gestation (2.30 ng/mL) with a p-value <0.001 and large effect size r=0.634. In contrast, among those with paired samples and HDP, the median suPAR level in early gestation (2.37 ng/mL) was not significantly different than late gestation (2.45 ng/mL) with a p-value=0.578 and small effect size r=0.256. It is notable however that the sample size of participants with repeated measures and HDP was small (n=7) and the timing of HDP onset was variable across participants. CONCLUSIONS:Although HDP is a primary cause of morbidity and mortality in pregnancy, predictive biomarkers are lacking. suPAR levels decrease with advancing gestation among healthy women, but remain stable in women with HDP, which may reflect a heightened inflammatory state. Additional research is needed to understand how suPAR correlates with other biomarkers of HDP and whether stable suPAR levels can predict HDP accurately in clinical practice.

OBJECTIVES/OBJECTIVE:We evaluated COVID-19 outcomes in children and young adults with type 1 diabetes (T1D) to determine if those with comorbidities are more likely to experience severe COVID-19 compared to those without. RESEARCH DESIGN AND METHODS/METHODS:This cross-sectional study included questionnaire data on patients <25 years of age with established T1D and laboratory-confirmed COVID-19 from 52 sites across the US between April 2020 and October 2021. We examined patient factors and COVID-19 outcomes between those with and without comorbidities. Multivariate logistic regression analysis examined the odds of hospitalization among groups, adjusting for age, HbA1c, race and ethnicity, insurance type and duration of diabetes. RESULTS:Six hundred fifty-one individuals with T1D and COVID-19 were analyzed with mean age 15.8 (SD 4.1) years. At least one comorbidity was present in 31%, and more than one in 10%. Obesity and asthma were the most frequently reported comorbidities, present in 19% and 17%, respectively. Hospitalization occurred in 17% of patients and 52% of hospitalized patients required ICU level care. Patients with at least one comorbidity were almost twice as likely to be hospitalized with COVID-19 than patients with no comorbidities (Odds ratio 2.0, 95% CI: 1.3-3.1). This relationship persisted after adjusting for age, HbA1c, race and ethnicity (minority vs nonminority), insurance type (public vs. private), and duration of diabetes. CONCLUSIONS:Our findings show that comorbidities increase the risk for hospitalization with COVID-19 in children and young adults highlighting the need for tailored COVID-19 prevention and treatment strategies in T1D.

Stress, in both intrinsic psychosocial and extrinsic physical environmental forms, can impact the development of, and outcomes in, cardiovascular disease (CVD) through allostatic load. Cortisol is a core hormonal mediator of allostatic load produced in response to various stresses. Alterations in morning serum cortisol and daily diurnal cortisol have been associated with adiposity, dyslipidemia, incident diabetes, and CVDs such as hypertension. The review examines the role of cortisol as a key mechanistic link between stress physiology and cardiometabolic disease. Importantly, we discuss the role of targeting cortisol through pharmacological, behavioral, and environmental interventions to advance health equity in cardiometabolic disease.

BACKGROUND:Prior research has demonstrated bidirectional associations between gestational diabetes mellitus (GDM) and perinatal maternal depression. However, the association between GDM, prenatal depression, and postpartum depression (PPD) has not been examined in a prospective cohort longitudinally. METHODS:Participants in the current analysis included 5,822 women from the National Institutes of Health's Environmental influences on Child Health Outcomes (ECHO) Research Program: N = 4,606 with Neither GDM nor Prenatal Maternal Depression (Reference Category); N = 416 with GDM only; N = 689 with Prenatal Maternal Depression only; and N = 111 with Comorbid GDM and Prenatal Maternal Depression. The PROMIS-D scale was used to measure prenatal and postnatal maternal depressive symptoms. Primary analyses consisted of linear regression models to estimate the independent and joint effects of GDM and prenatal maternal depression on maternal postpartum depressive symptoms. RESULTS:A higher proportion of women with GDM were classified as having prenatal depression (N = 111; 21%) compared to the proportion of women without GDM who were classified as having prenatal depression (N = 689; 13%), however this finding was not significant after adjustment for covariates. Women with Comorbid GDM and Prenatal Maternal Depression had significantly increased postpartum depressive symptoms measured by PROMIS-D T-scores compared to women with Neither GDM nor Prenatal Maternal Depression (mean difference 7.02, 95% CI 5.00, 9.05). Comorbid GDM and Prenatal Maternal Depression was associated with an increased likelihood of PPD (OR 7.38, 95% CI 4.05, 12.94). However, women with GDM only did not have increased postpartum PROMIS-D T-scores or increased rates of PPD. CONCLUSIONS:Our findings underscore the importance of universal depression screening during pregnancy and in the first postpartum year. Due to the joint association of GDM and prenatal maternal depression on risk of PPD, future studies should examine potential mechanisms underlying this relation.

Background: Interventions for carotid occlusions are infrequently undertaken and the outcomes are poorly defined. We sought to study patients undergoing urgent carotid revascularization for symptomatic occlusions.
Method(s): The Society for Vascular Surgery Vascular Quality Initiative was queried from 2003 to 2020 to identify patients with carotid occlusions undergoing carotid endarterectomy. Only symptomatic patients undergoing urgent interventions, defined within 24 hours of presentation, were included in this analysis. This cohort was compared to patients undergoing urgent intervention for severe stenosis (>=80%). Patients were identified based on computed tomography and magnetic resonance imaging, only. The primary end points were perioperative stroke, death, myocardial infarction (MI), and composite outcomes.
Result(s): A total of 390 patients were identified who underwent urgent carotid endarterectomy for symptomatic occlusions. The mean age was 67.4 +/- 10.2 years with a range from 39 to 90 years. The cohort was predominantly male (60%), and had significant risk factors for cerebrovascular disease, including hypertension (87.4%), diabetes (34.4%), coronary artery disease (21.6%), current smoking (38.7%), chronic obstructive pulmonary disease (21.6%), and congestive heart failure (10.3%). Medications included statin therapy (78.6%), P2Y12 inhibitors (32.0%), aspirin (77.9%) and renin-angiotensin inhibitor use (43.7%). The perioperative rate of neurologic events was 4.9%%, associated mortality was 2.8% and rate of MI was 1.0%. The composite end point of stroke/death/MI was 7.7%. When compared to patients undergoing urgent endarterectomy for severe stenosis (>=80%), the two cohorts were well matched with regards to risk factors, but the severe stenosis cohort appeared to be better medically managed based on reported medications. In the severe stenosis group, the perioperative rate of neurologic events was 3.3%, associated mortality was 0.9% and rate of MI was 1.2%. The perioperative outcomes were significantly worse for the carotid occlusion cohort, primarily driven by the perioperative mortality, which was nearly threefold, 2.8% versus 0.9% (P <.001). The composite end point of stroke/death/MI was also significantly worse in the occlusion cohort (7.7% vs 4.9%; P =.014).
Conclusion(s): Revascularization for symptomatic carotid occlusion constitutes approximately 2% of carotid interventions captured in the Vascular Quality Initiative, affirming the rarity of this undertaking. These patients have acceptable rates of perioperative neurologic events but are at an elevated risk of overall perioperative adverse events, primarily driven by a significantly higher mortality. While intervention for a symptomatic carotid occlusion may be performed with acceptable rate of perioperative complications, judicious patient selection is warranted in this high-risk cohort.
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Limited studies have focused on maternal early-life risk factors and the later development of gestational diabetes mellitus (GDM). We aimed to estimate the GDM prevalence and examine the associations of maternal early-life risk factors, namely: maternal birthweight, parental smoking at birth, childhood urbanicity, ever-breastfed, parental education attainment, parental history of diabetes, childhood overall health, childhood body size, and childhood height, with later GDM. This was a retrospective cross-sectional study using the UAE Healthy Future Study (UAEHFS) baseline data (February 2016 to April 2022) on 702 ever-married women aged 18 to 67 years. We fitted a Poisson regression to estimate the risk ratio (RR) for later GDM and its 95% confidence interval (CI). The GDM prevalence was 5.1%. In the fully adjusted model, females with low birthweight were four times more likely (RR 4.04, 95% CI 1.36-12.0) and females with a parental history of diabetes were nearly three times more likely (RR 2.86, 95% CI 1.10-7.43) to report later GDM. In conclusion, maternal birthweight and parental history of diabetes were significantly associated with later GDM. Close glucose monitoring during pregnancy among females with either a low birth weight and/or parental history of diabetes might help to prevent GDM among this high-risk group.

INTRODUCTION/BACKGROUND:The aim of this research was to assess the association between inflammation and oral health and diabetes, as well as the mediating role of oral hygiene practice in this association. METHODS:Data were from the 2009-2010 National Health and Nutrition Examination Survey. The analytical sample consisted of 2,191 respondents aged 50 and older. Poor oral health was clinically defined by significant tooth loss (STL) and periodontal disease (PD). Diabetes mellitus (DM) was determined by glycemic levels. The outcome variable was serum C-reactive protein (CRP) level, dichotomised as ≥1 mg/dL (elevated CRP) vs <1 mg/dL (not elevated CRP). Two path models, one using STL and DM as the independent variable, the other using PD and DM as the independent variable, were estimated to assess the direct effects of having poor oral health and DM on elevated CRP and the mediating effects of dental flossing. RESULTS:In path model 1, individuals having both STL and DM (adjusted odds ratio [AOR], 1.92; 95% confidence interval [CI], 1.30-2.82) or having STL alone (AOR, 2.30; 95% CI, 1.68-3.15) were more likely to have elevated CRP than those with neither STL nor DM; dental flossing (AOR, 0.92, 95% CI, 0.88-0.96) was associated with lower risk of elevated CRP. In path model 2, no significant association was found between having both PD and DM and elevated CRP; dental flossing (AOR, 0.91; 95% CI:, 0.86-0.94) was associated with lower risk of elevated CRP. CONCLUSIONS:Findings from this study highlight the importance of improving oral health and oral hygiene practice to mitigate inflammation. Further research is needed to assess the longer-term effects of reducing inflammation.

BACKGROUND/OBJECTIVES/OBJECTIVE:Excessive gestational weight gain (GWG) and pre-pregnancy obesity affect a significant portion of the US pregnant population and are linked with negative maternal and child health outcomes. The objective of this study was to explore associations of pre-pregnancy body mass index (pBMI) and GWG with longitudinally measured maternal urinary metabolites throughout pregnancy. SUBJECTS/METHODS/METHODS:Among 652 participants in the New York University Children's Health and Environment Study, a longitudinal pregnancy cohort, targeted metabolomics were measured in serially collected urine samples throughout pregnancy. Metabolites were measured at median 10 (T1), 21 (T2), and 29 (T3) weeks gestation using the Biocrates AbsoluteIDQ® p180 Urine Extension kit. Acylcarnitine, amino acid, biogenic amine, phosphatidylcholine, lysophosphatidylcholine, sphingolipid, and sugar levels were quantified. Pregnant people 18 years or older, without type 1 or 2 diabetes and with singleton live births and valid pBMI and metabolomics data were included. GWG and pBMI were calculated using weight and height data obtained from electronic health records. Linear mixed effects models with interactions with time were fit to determine the gestational age-specific associations of categorical pBMI and continuous interval-specific GWG with urinary metabolites. All analyses were corrected for false discovery rate. RESULTS:Participants with obesity had lower long-chain acylcarnitine levels throughout pregnancy and lower phosphatidylcholine and glucogenic amino acids and higher phenylethylamine concentrations in T2 and T3 compared with participants with normal/underweight pBMI. GWG was associated with taurine in T2 and T3 and C5 acylcarnitine species, C5:1, C5-DC, and C5-M-DC, in T2. CONCLUSIONS:pBMI and GWG were associated with the metabolic environment of pregnant individuals, particularly in relation to mid-pregnancy. These results highlight the importance of both preconception and prenatal maternal health.

OBJECTIVE:We examined United States (US) trends in diabetic ketoacidosis (DKA) among individuals with type 1 diabetes (T1D) during the COVID-19 pandemic at seven large US medical centers and factors associated with these trends. METHODS:We compared DKA events among children and adults with T1D during COVID-19 surge 1 (March-May 2020) and COVID-19 surge 2 (August-October 2020) to the same periods in 2019. Analysis was performed using descriptive statistics and Chi-square tests. RESULTS:We found no difference in the absolute number of T1D patients experiencing DKA in 2019 vs 2020. However, a higher proportion of non-Hispanic Blacks (NHB) experienced DKA in 2019 than non-Hispanic Whites (NHW) (44.6% vs 16.0%; p<0.001), and this disparity persisted during the COVID-19 pandemic (48.6% vs 18.6%; p<0.001). DKA was less common among patients on continuous glucose monitor (CGM) or insulin pump in 2020 compared to 2019 (CGM: 13.2% vs 15.0%, p<0.001; insulin pump: 8.0% vs 10.6%, p<0.001). In contrast to annual DKA totals, a higher proportion of patients had DKA during COVID-19 surges 1 and 2 compared to the same months in 2019 (surge 1: 7.1% vs 5.4%, p<0.001; surge 2: 6.6% vs 5.7%, p=0.001). CONCLUSIONS:DKA frequency increased among T1D patients during COVID-19 surges with highest frequency among NHB. DKA was less common among patients using CGM or insulin pumps. These findings highlight the urgent need for improved strategies to prevent DKA among patients with T1D-not only under pandemic conditions, but under all conditions-especially among populations most affected by health inequities.