Faculty Bibliography

PURPOSE/OBJECTIVE:To report the effects of pegvisomant (PEGV) treatment on patient-reported outcomes in acromegaly patients. METHODS:We conducted an extension study of an open-label, multinational, non-interventional study (ACROSTUDY) evaluating the long-term safety and efficacy of PEGV for acromegaly in routine clinical practice. Enrolled patients were rollover patients from ACROSTUDY, or treatment naïve/semi-naïve (NSN; no PEGV within 6 months of enrollment). Exploratory efficacy endpoints were changes in symptoms with the Patient-Assessed Acromegaly Symptom Questionnaire (PASQ) and quality of life with the Acromegaly Quality of Life questionnaire (AcroQoL) analyzed by controlled or uncontrolled IGF-I levels. Results were analyzed in all patients, in NSN patient subgroup, and by diabetes status. RESULTS:A total of 544 patients with acromegaly were enrolled, including 434 rollover subjects from ACROSTUDY and 110 NSN patients. Mean PEGV treatment duration was 7.8 years (range, 0-19.6 years). Overall, the majority of PASQ scores improved over time, but there was no significant difference between IGF-I controlled or uncontrolled groups. In the NSN subgroup, most PASQ and AcroQoL scores remained similar to baseline up to 1 year, regardless of IGF-I control. Patients with diabetes reported better PASQ scores over time with PEGV treatment, regardless of IGF-I control. IGF-I normalization increased from 10% of patients at baseline to more than 78% at year 10, with a mean daily PEGV dose of 18.7 mg. CONCLUSIONS:Overall, patients treated with PEGV had small improvements in PASQ. While IGF-I normalization increased with PEGV treatment, IGF-I control had no effects on PASQ and AcroQoL scores.

BACKGROUND:An increase in newly diagnosed type 1 diabetes (T1D) has been posited during the COVID-19 pandemic, but data are conflicting. We aimed to determine trends in newly diagnosed T1D and severity of presentation at diagnosis for pediatric and adolescent patients during COVID-19 (2020) as compared to the previous year (2019) in a multi-center analysis across the United States. METHODS:This retrospective study from seven centers in the T1D Exchange Quality Improvement Collaborative (T1DX-QI) included data on new onset T1D diagnosis and proportion in DKA at diagnosis from January 1 to December 31, 2020, compared to the prior year. Chi-square tests were used to compare differences in patient characteristics during the pandemic period compared to the prior year. RESULTS:Across seven sites, there were 1399 newly diagnosed T1D patients in 2020, compared to 1277 in 2019 (p=0.007). A greater proportion of newly diagnosed patients presented in DKA in 2020 compared to 2019 (599/1399(42.8%) v. 493/1277(38.6%), p=0.02), with a higher proportion presenting with severe DKA (p=0.01) as characterized by a pH<7.1 and/or bicarbonate of <5mmol/L. Monthly data trends demonstrated a higher number of new T1D diagnoses over the spring and summer months (March to September) of 2020 compared to 2019 (p<0.001). CONCLUSIONS:We found an increase in newly diagnosed T1D and a greater proportion presenting in DKA at diagnosis during the COVID-19 pandemic compared to the prior year. Future longitudinal studies are needed to confirm these findings with population level data and determine the long-term impact of COVID-19 on diabetes trends. This article is protected by copyright. All rights reserved.

BACKGROUND/UNASSIGNED:The obesity increased incidence of diabetes, hypertension and atherosclerosis and rate of morbidity and mortality. The main cause of atherosclerosis is endothelial dysfunction and formation of foam cells and macrophage that lead to unfavorable complications. This study evaluated specific biomarkers for endothelial dysfunction as sensitive indices for early predication of atherosclerosis in obese subjects. STUDY DESIGN/UNASSIGNED:One hundred fifty male age and sex matching were included in the current study divided into three groups according to body mass index (BMI): Control (BMI ≤ 22), obese (BMI> 28) and obese with atherosclerosis (BMI> 28). Fasting serum was subjected for determination of adhesion molecules, sICAM-1, sVCAM-1, E-selectin, oxo-LDL and 8-iso-PGF2α by ELISA technique. RESULTS/UNASSIGNED:Data obtained showed that, a significant elevation of serum inflammatory markers CRP, IL-6 and TNF-α and adhesion molecules sICAM-1 (p<0.001) with sensitivity 96%, sVCAM-1 (p <0.01) with sensitivity 92%, E-selectin (p<0.001) with sensitivity 94%, oxo-LDL (p <0.05) and 8-iso-PGF2α (p < 0.001) with sensitivity 97% in obese with atherosclerosis compared with obese and control. CONCLUSION/UNASSIGNED:The levels of serum adhesion molecules contributed in the pathogenesis of endothelial dysfunction can be used as sensitive biomarkers for early prediction of atherosclerosis in obese subjects.

BACKGROUND:People with cystic fibrosis (pwCF) may be at risk of complications from COVID-19 but the impact of COVID-19 on pwCF remains unknown. METHODS:We conducted a multicenter retrospective cohort study to assess the impact of the COVID-19 pandemic first wave on pwCF in the New York metropolitan area (NY) from March 1, 2020 to August 31, 2020. Objectives were to determine (1) the prevalence of COVID-19 by PCR and IgG antibody testing, (2) the clinical characteristics of COVID-19, (3) delay in routine outpatient care, and (4) the effect on anxiety and depression in pwCF. RESULTS:There were 26 COVID-19 cases diagnosed by PCR or antibody testing among the study cohort of 810 pwCF. The prevalence of COVID-19 by PCR (1.6%) and IgG antibody (12.2%) testing was low. 58% of cases were asymptomatic and 82% were managed at home. 8% were hospitalized and 1 person died. 89% of pwCF experienced delay in care. The prevalence of anxiety increased from 43% baseline to 58% during the pandemic (P<0.01). In post-hoc analysis, the proportion of patients with diabetes (38% versus 16%, P<0.01) and pancreatic insufficiency (96% versus 66%, P<0.01) were higher while CFTR modulator use was lower (46% versus 65%, P = 0.05) in pwCF who tested positive for COVID-19. CONCLUSIONS:The prevalence of COVID-19 among pwCF in NY during the pandemic first wave was low and most cases were managed at home. CFTR modulators may be protective. PwCF experienced delay in routine care and increased anxiety.

AIMS/OBJECTIVE:Individuals with type 1 diabetes (T1D) face increased risk for cardiovascular disease (CVD). Controlling individual cardiovascular risk factors can prevent or slow the onset of CVD. Ideal cardiovascular health is associated with a lower incidence of CVD. Identifying areas of suboptimal cardiovascular health can help guide CVD prevention interventions. To assess cardiovascular health and explore the barriers and facilitators to achieving ideal cardiovascular health in a sample of young adults with T1D. METHODS AND RESULTS/RESULTS:We used a sequential mixed-method design to assess the seven factors of cardiovascular health according to American Heart Association. Qualitative interviews, guided by Pender's Health Promotion Model, were used to discuss participant's cardiovascular health results and the barriers and facilitators to achieving ideal cardiovascular health. We assessed the frequency of ideal levels of each factor. The qualitative data were analysed using content analysis. Qualitative and quantitative data were integrated in the final analysis phase. The sample (n = 50) was majority female (70%), White (86%), with a mean age of 22 ± 2.4 and diabetes duration of 10.7 ± 5.5 years. Achievement of the seven factors of cardiovascular health were: non-smoking (96%); cholesterol <200 mg/dL (76%); body mass index <25 kg/m2 (54%); blood pressure <120/<80 mmHg (46%); meeting physical activity guidelines (38%); haemoglobin A1c <7% (40%); and healthy diet (14%). Emerging qualitative themes related to the perceived benefits of action, interpersonal influences on their diabetes self-management, and perceived self-efficacy. CONCLUSION/CONCLUSIONS:We found areas of needed improvement for cardiovascular health. However, these young adults expressed a strong interest in healthy habits which can be supported by their healthcare providers.

Environmental chemical exposures have been associated with cancer, diabetes, hormonal and immunological disorders, and cardiovascular diseases. Some direct effects of chemical exposure that are precursors to adverse health outcomes, including oxidative stress, nitrative stress, hormonal imbalance, neutrophilia, and eosinophilia, can be assessed through the analysis of biomarkers in urine. In this study, we describe a novel methodology for the determination of 19 biomarkers of health effects: malondialdehyde (MDA), 8-isoprostaglandin-F_2α (8-PGF_2α), 11-β-prostaglandin-F_2α (11-PGF_2α), 15-prostaglandin-F_2α (15-PGF_2α), 8-iso-15-prostaglandin-F_2α (8,15-PGF_2α), 8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-hydroxyguanosine (8-HdG), 8-hydroxyguanine (8-HG), dityrosine (diY), allantoin (Alla), and two metabolic products of 4-hydroxynonenal (HNE), namely 4-hydroxy-2-nonenal glutathione (HNE-GSH) and 4-hydroxy-2-nonenal mercapturic acid (HNE-MA) (in total, 12 oxidative stress biomarkers, OSBs); 8-nitroguanosine (8-NdG), 8-nitroguanine (8-NG), and 3-nitrotyrosine (NY) (3 nitrative stress biomarkers, NSBs); chlorotyrosine (CY) and bromotyrosine (BY) (2 inflammatory biomarkers); and the advanced glycation end-products (AGEs) N^ε-carboxymethyllysine (CML) and N^ε-carboxyethyllysine (CEL) (2 metabolic disorder biomarkers). Since these biomarkers are trigged by a variety of environmental insults and produced by different biomolecular pathways, their selective and sensitive determination in urine would help broadly elucidate the pathogenesis of diseases mediated by environmental factors.

CONTEXT:COVID-19 morbidity and mortality are increased in type 1 diabetes (T1D), but few data focus on age-based outcomes. OBJECTIVE:This work aimed to quantify the risk for COVID-19-related hospitalization and adverse outcomes by age in people with T1D. METHODS:For this observational, multisite, cross-sectional study of patients with T1D and laboratory-confirmed COVID-19 from 56 clinical sites in the United States, data were collected from April 2020 to March 2021. The distribution of patient factors and outcomes across age groups (0-18, 19-40, and > 40 years) was examined. Descriptive statistics were used to describe the study population, and multivariate logistic regression models were used to analyze the relationship between age, adverse outcomes, and hospitalization. The main outcome measure was hospitalization for COVID-19. RESULTS:A total of 767 patients were analyzed. Fifty-four percent (n = 415) were aged 0 to 18 years, 32% (n = 247) were aged 19 to 40 years, and 14% (n = 105) were older than 40 years. A total of 170 patients were hospitalized, and 5 patients died. Compared to the 0- to 18-years age group, those older than 40 years had an adjusted odds ratio of 4.2 (95% CI, 2.28-7.83) for hospitalization after adjustment for sex, glycated hemoglobin A1c, race, insurance type, and comorbidities. CONCLUSION:Age older than 40 years is a risk factor for patients with T1D and COVID-19, with children and younger adults experiencing milder disease and better prognosis. This indicates a need for age-tailored treatments, immunization, and clinical management of individuals affected by T1D.

CONTEXT/BACKGROUND:Phthalates may disrupt maternal-fetal-placental endocrine pathways, affecting pregnancy outcomes and child development. Placental corticotropin releasing hormone (pCRH) is critical for healthy pregnancy and child development, but understudied as a target of endocrine disruption. OBJECTIVE:To examine phthalate metabolite concentrations (as mixtures and individually) in relation to pCRH. DESIGN/METHODS:Secondary data analysis from a prospective cohort study. SETTING/METHODS:Prenatal clinics in Tennessee, USA. PATIENTS/METHODS:1018 pregnant women (61.4% non-Hispanic Black, 32% non-Hispanic White, 6.6% other) participated in the CANDLE study and provided data. Inclusion criteria included: low-medical-risk singleton pregnancy, age 16-40, and gestational weeks 16-29. INTERVENTION/METHODS:None. MAIN OUTCOME MEASURES/METHODS:Plasma pCRH at two visits (mean gestational ages 23.0 and 31.8 weeks) and change in pCRH between visits (ΔpCRH). RESULTS:In weighted quantile sums (WQS) regression models, phthalate mixtures were associated with higher pCRH at Visit 1 (β = 0.07, 95 %CI: 0.02, 0.11) but lower pCRH at Visit 2 (β = -0.08, 95 %CI: -0.14, -0.02). In stratified analyses, among women with gestational diabetes (n = 59), phthalate mixtures were associated with lower pCRH at Visit 1 (β = -0.17, 95 %CI: -0.35, 0.0006) and Visit 2 (β = -0.35, 95 %CI: -0.50, -0.19), as well as greater ΔpCRH (β = 0.16, 95 %CI: 0.07, 0.25). Among women with gestational hypertension (n = 102), phthalate mixtures were associated with higher pCRH at Visit 1 (β = 0.20, 95 %CI: 0.03, 0.36) and Visit 2 (β = 0.42; 95 %CI: 0.19, 0.64) and lower ΔpCRH (β = -0.17, 95 %CI: -0.29, -0.06). Significant interactions between individual phthalate metabolites and pregnancy complications were observed. CONCLUSIONS:Phthalates may impact placental CRH secretion, with differing effects across pregnancy. Differences in results between women with and without gestational diabetes and gestational hypertension suggest a need for further research examining whether women with pregnancy complications may be more vulnerable to endocrine-disrupting effects of phthalates.

Background: Patient outcomes of COVID-19 have improved throughout the pandemic. However, because it is not known whether outcomes of COVID-19 in the type 1 diabetes (T1D) population improved over time, we investigated differences in COVID-19 outcomes for patients with T1D in the United States. Methods: We analyzed data collected via a registry of patients with T1D and COVID-19 from 56 sites between April 2020 and January 2021. We grouped cases into first surge (April 9, 2020, to July 31, 2020, n = 188) and late surge (August 1, 2020, to January 31, 2021, n = 410), and then compared outcomes between both groups using descriptive statistics and logistic regression models. Results: Adverse outcomes were more frequent during the first surge, including diabetic ketoacidosis (32% vs 15%, P< .001), severe hypoglycemia (4% vs 1%, P= .04), and hospitalization (52% vs 22%, P< .001). Patients in the first surge were older (28 [SD,18.8] years vs 18.0 [SD, 11.1] years, P< .001), had higher median hemoglobin A1c levels (9.3 [interquartile range {IQR}, 4.0] vs 8.4 (IQR, 2.8), P< .001), and were more likely to use public insurance (107 [57%] vs 154 [38%], P< .001). The odds of hospitalization for adults in the first surge were 5 times higher compared to the late surge (odds ratio, 5.01; 95% CI, 2.11-12.63). Conclusion: Patients with T1D who presented with COVID-19 during the first surge had a higher proportion of adverse outcomes than those who presented in a later surge.

Obesity and type 2 diabetes mellitus are highly prevalent and increasing in the United States among racial/ethnic minority groups. Type 2 diabetes mellitus, which is driven by many factors including elevated levels of adiposity, is an exemplar health disparities disease. Pervasive disparities exist at every level from risk factors through outcomes for U.S. racial/ethnic minority groups, including African American, Hispanic/LatinX American, and Asian American populations. Disparities in clinical care exist including hemoglobin A1c control, lower prescription rates of newer antihyperglycemic medications, along with greater rates of complications postbariatric surgery. Underpinning these disparities are the social determinants of health affecting provider-patient interactions, access to resources, and healthy built environments. We review the best practices to address cardiometabolic disparities in the current cardiovascular guidelines and describe recommendations for cross-cutting strategies to advance equity in obesity and type 2 diabetes across U.S. racial/ethnic groups.