The Women's Leadership Gap in Diabetes: A Call for Equity and Excellence.

Women are broadly underrepresented in scientific leadership positions and their accomplishments are not provided equal recognition compared with those of men, but the imbalance in the field of diabetes is unknown. Hence, we analyzed multiple aspects of historical and present-day female representation in the diabetes field.We quantified gender representation at annual American Diabetes Association (ADA) meetings; editorial board service positions for ADA and the European Association for the Study of Diabetes (EASD) journals; principal investigators for ADA, JDRF, and National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases P30 grant funding; and ADA, JDRF, and EASD award recipients. There are many women in the field of diabetes: registration for the ADA Scientific Sessions has been 43% female since 2016, and for over five decades, women comprised 83% of ADA Presidents of Health Care and Education. Yet, only 9% of ADA Presidents of Medicine and Science have been women. Women were well represented on editorial boards for journals focused on diabetes education (Diabetes Spectrum, 89% female) and primary care (Clinical Diabetes, 49% female) but not for the more academically targeted Diabetes Care (34% female), Diabetes (21% female), and Diabetologia (30% female). Only one-third of ADA Pathway to Stop Diabetes and JDRF grants have been awarded to women, and females only lead 2 of 18 (11%) of the P30-supported Diabetes Research Centers. Finally, only 2-12% of major ADA, JDRF, and EASD awards were given to women, without significant change over time. Despite increasing recognition of gender imbalance in research and medicine, many disparities in the field of diabetes persist. We call for decreasing barriers for advancement of female investigators and creating environments that promote their retention and equitable recognition for their contributions to the field.

Phenotypes of disease severity in a cohort of hospitalized COVID-19 patients: Results from the IMPACC study.

BACKGROUND: Better understanding of the association between characteristics of patients hospitalized with coronavirus disease 2019 (COVID-19) and outcome is needed to further improve upon patient management. METHODS: Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) is a prospective, observational study of 1164 patients from 20 hospitals across the United States. Disease severity was assessed using a 7-point ordinal scale based on degree of respiratory illness. Patients were prospectively surveyed for 1 year after discharge for post-acute sequalae of COVID-19 (PASC) through quarterly surveys. Demographics, comorbidities, radiographic findings, clinical laboratory values, SARS-CoV-2 PCR and serology were captured over a 28-day period. Multivariable logistic regression was performed. FINDINGS: The median age was 59 years (interquartile range [IQR] 20); 711 (61%) were men; overall mortality was 14%, and 228 (20%) required invasive mechanical ventilation. Unsupervised clustering of ordinal score over time revealed distinct disease course trajectories. Risk factors associated with prolonged hospitalization or death by day 28 included age ≥ 65 years (odds ratio [OR], 2.01; 95% CI 1.28-3.17), Hispanic ethnicity (OR, 1.71; 95% CI 1.13-2.57), elevated baseline creatinine (OR 2.80; 95% CI 1.63- 4.80) or troponin (OR 1.89; 95% 1.03-3.47), baseline lymphopenia (OR 2.19; 95% CI 1.61-2.97), presence of infiltrate by chest imaging (OR 3.16; 95% CI 1.96-5.10), and high SARS-CoV2 viral load (OR 1.53; 95% CI 1.17-2.00). Fatal cases had the lowest ratio of SARS-CoV-2 antibody to viral load levels compared to other trajectories over time (p=0.001). 589 survivors (51%) completed at least one survey at follow-up with 305 (52%) having at least one symptom consistent with PASC, most commonly dyspnea (56% among symptomatic patients). Female sex was the only associated risk factor for PASC. INTERPRETATION: Integration of PCR cycle threshold, and antibody values with demographics, comorbidities, and laboratory/radiographic findings identified risk factors for 28-day outcome severity, though only female sex was associated with PASC. Longitudinal clinical phenotyping offers important insights, and provides a framework for immunophenotyping for acute and long COVID-19. FUNDING: NIH.

Incidence Trends of New-Onset Diabetes in Children and Adolescents Before and During the COVID-19 Pandemic: Findings From Florida.

This study examined the incidence trends of new-onset type 1 and type 2 diabetes in children and adolescents in Florida before and during the coronavirus disease 2019 (COVID-19) pandemic. In this observational descriptive cohort study, we used a validated computable phenotype to identify incident diabetes cases among individuals <18 years of age in the OneFlorida+ network of the national Patient-Centered Clinical Research Network between January 2017 and June 2021. We conducted an interrupted time series analysis based on the autoregressive integrated moving average model to compare changes in age-adjusted incidence rates of type 1 and type 2 diabetes before and after March 2020, when COVID-19 was declared a national health emergency in the U.S. The age-adjusted incidence rates of both type 1 and type 2 diabetes increased post-COVID-19 for children and adolescents. These results highlight the need for longitudinal cohort studies to examine how the pandemic might influence subsequent diabetes onset in young individuals.

Limited extent and consequences of pancreatic SARS-CoV-2 infection.

Concerns that infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of coronavirus disease 2019 (COVID-19), may cause new-onset diabetes persist in an evolving research landscape, and precise risk assessment is hampered by, at times, conflicting evidence. Here, leveraging comprehensive single-cell analyses of in vitro SARS-CoV-2-infected human pancreatic islets, we demonstrate that productive infection is strictly dependent on the SARS-CoV-2 entry receptor ACE2 and targets practically all pancreatic cell types. Importantly, the infection remains highly circumscribed and largely non-cytopathic and, despite a high viral burden in infected subsets, promotes only modest cellular perturbations and inflammatory responses. Similar experimental outcomes are also observed after islet infection with endemic coronaviruses. Thus, the limits of pancreatic SARS-CoV-2 infection, even under in vitro conditions of enhanced virus exposure, challenge the proposition that in vivo targeting of ß cells by SARS-CoV-2 precipitates new-onset diabetes. Whether restricted pancreatic damage and immunological alterations accrued by COVID-19 increase cumulative diabetes risk, however, remains to be evaluated.

ACE2 chromogenic immunostaining protocol optimized for formalin-fixed paraffin-embedded human tissue sections.

Angiotensin-converting enzyme 2 (ACE2) is a key cellular entry factor for severe acute respiratory syndrome coronavirus 2. Hence, identifying cell types that express ACE2 is important for understanding the pathophysiology of coronavirus disease 2019. We performed extensive testing of multiple primary antibodies across various human tissue types. Here, we describe an optimized protocol for immunostaining of ACE2 in formalin-fixed paraffin-embedded human pancreas, small intestine, and kidney tissue sections obtained from organ donors and autopsies. For complete details on the use and execution of this protocol, please refer to Kusmartseva et al. (2020).

Voices: Insulin and beyond.

Marking insulin's centennial, we share stories of researchers and clinicians whose seminal work has advanced our understanding of insulin, islet biology, insulin resistance, and diabetes. The past century of pursuing the "hormone of hormones" and advancing diabetes therapies is replete with stories of collaboration, perseverance, and triumph.

The influence of selection bias on identifying an association between allergy medication use and SARS-CoV-2 infection.

BACKGROUND: Medications to prevent and treat SARS-CoV-2 infection are needed to complement emerging vaccinations. Recent in vitro and electronic health record (EHR) studies suggested that certain allergy medications could prevent SARS-CoV-2 infection. We sought to carefully examine the potential selection bias associated with utilizing EHRs in these settings. METHODS: We analyzed associations of three allergy medications (cetirizine, diphenhydramine or hydroxyzine) with testing negative for SARS-CoV-2, measuring the potential effect of selection bias on these associations. We used a retrospective cohort of EHR data from 230,376 patients (18 years+) who visited outpatient clinicians in a single, large academic center at least once but were never hospitalized (10/1/2019-6/1/2020). Main exposures included EHR documentation of three allergy medications and allergy, with an intermediate outcome of receipt of a SARS-CoV-2 test, and the primary outcome as testing negative. FINDINGS: SARS-CoV-2 testing rates varied by sex, age, race/ethnicity and insurance. Increasing age and public insurance were associated with a higher adjusted odds of test negativity, while being Black or Hispanic was significantly associated with test positivity. Allergy diagnosis and use of any of three allergy medications were each associated with a higher likelihood of receiving a test (e.g. diphenhydramine - Odds Ratio (OR) 2.99, 95% Confidence Interval (CI) 2.73, 3.28; cetirizine 1.75 (95% CI 1.60, 1.92)). Among those tested, only use of diphenhydramine was associated with a negative SARS-CoV-2 test (adjusted OR = 2.23, 95% CI 1.10, 4.55). However, analyses revealed that selection bias may be responsible for the apparent protective effect of diphenhydramine. INTERPRETATION: Diphenhydramine use was associated with more SARS-CoV-2 testing and subsequent higher odds for negative tests. While EHR-based observational studies can inform a need for interventional trials, this study revealed limitations of EHR data. The finding that diphenhydramine documentation conferred a higher odds of testing negative for SARS-CoV-2 must be interpreted with caution due to probable selection bias.Abbreviations: SARS-CoV-2, ACE2, COVID-19, EHR.

Expression of SARS-CoV-2 Entry Factors in the Pancreas of Normal Organ Donors and Individuals with COVID-19.

Diabetes is associated with increased mortality from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Given literature suggesting a potential association between SARS-CoV-2 infection and diabetes induction, we examined pancreatic expression of angiotensin-converting enzyme 2 (ACE2), the key entry factor for SARS-CoV-2 infection. Specifically, we analyzed five public scRNA-seq pancreas datasets and performed fluorescence in situ hybridization, western blotting, and immunolocalization for ACE2 with extensive reagent validation on normal human pancreatic tissues across the lifespan, as well as those from coronavirus disease 2019 (COVID-19) cases. These in silico and ex vivo analyses demonstrated prominent expression of ACE2 in pancreatic ductal epithelium and microvasculature, but we found rare endocrine cell expression at the mRNA level. Pancreata from individuals with COVID-19 demonstrated multiple thrombotic lesions with SARS-CoV-2 nucleocapsid protein expression that was primarily limited to ducts. These results suggest SARS-CoV-2 infection of pancreatic endocrine cells, via ACE2, is an unlikely central pathogenic feature of COVID-19-related diabetes.