Understanding Providers' Readiness and Attitudes Toward Autoantibody Screening: A Mixed-Methods Study.

Screening for autoantibodies associated with type 1 diabetes can identify people most at risk for progressing to clinical type 1 diabetes and provide an opportunity for early intervention. Drawbacks and barriers to screening exist, and concerns arise, as methods for disease prevention are limited and no cure exists today. The availability of novel treatment options such as teplizumab to delay progression to clinical type 1 diabetes in high-risk individuals has led to the reassessment of screening programs. This study explored awareness, readiness, and attitudes of endocrinology providers toward type 1 diabetes autoantibody screening.

Insulin Pump Utilization in 2017-2021 for More Than 22,000 Children and Adults With Type 1 Diabetes: A Multicenter Observational Study.

This large type 1 diabetes cohort study showed that insulin pump utilization has increased over time and that use differs by sex, insurance type, and race/ethnicity. Insulin pump use was associated with more optimal A1C, increased use of continuous glucose monitoring (CGM), and lower rates of diabetic ketoacidosis and severe hypoglycemia. People who used an insulin pump with CGM had lower rates of acute events than their counterparts who used an insulin pump without CGM. These findings highlight the need to improve access of diabetes technology through provider engagement, multidisciplinary approaches, and efforts to address health inequities.

Institutional Barriers to the Successful Implementation of Telemedicine for Type 1 Diabetes Care.

The aim of this study was to describe rates of telemedicine use 18 months after the start of the coronavirus disease 2019 pandemic and to assess the institutional barriers to its implementation for type 1 diabetes care across centers of the T1D Exchange Quality Improvement Collaborative. Observational electronic health record data capturing telemedicine rates from 15 U.S. centers between September 2020 and September 2021 and a survey of 33 centers capturing telemedicine rates and key components of telemedicine were analyzed. A capacity score was developed and summed to a total capacity score and compared with overall telemedicine rates across centers. Telemedicine visits decreased by 17.4% from September 2020 to September 2021. Generally, it was observed that the lower the average telemedicine capacity score, the lower the rate of telemedicine visits. Despite a decline in the utilization of telemedicine 18 months after the start of the pandemic, visit rates were still 20% higher than in the pre-pandemic period. However, there is a need to improve structural components to ensure telemedicine capacity and robust telemedicine utilization.

Increase in newly diagnosed type 1 diabetes in youth during the COVID-19 pandemic in the United States: A multi-center analysis.

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%) vs. 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 <5 mmol/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.

Comorbidities increase COVID-19 hospitalization in young people with type 1 diabetes.

OBJECTIVES: 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: 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.

Factors Associated With Achieving Target A1C in Children and Adolescents With Type 1 Diabetes: Findings From the T1D Exchange Quality Improvement Collaborative.

The optimal care of type 1 diabetes involves consistent glycemic management to avoid short- and long-term complications. However, despite advancements in diabetes technology and standards, achieving adequate glycemic levels in children and adolescents remains a challenge. This study aimed to identify factors associated with achieving the recommended A1C target of <7% from the United States-based multicenter T1D Exchange Quality Improvement Collaborative cohort, including 25,383 children and adolescents living with type 1 diabetes.

Facilitators and Barriers to Smart Insulin Pen Use: A Mixed-Method Study of Multidisciplinary Stakeholders From Diabetes Teams in the United States.

This study sought to identify barriers and facilitators to successful smart insulin pen (SIP) use and gauge prescribing practices and integration into clinical practice by assessing provider and care team perspectives at participating endocrinology clinics within the T1D Exchange Quality Improvement Collaborative. The identified provider-related, patient-related, and clinic- and operational-level barriers and facilitators varied based on clinic knowledge, capacity, and resources. High-impact barriers included insurance coverage and prescribing processes; high-impact facilitators included improved diabetes clinic visit quality and use of SIPs as an alternative to insulin pump therapy. Findings indicated the need for provider and care team education and training on proper SIP features, use, and prescribing.

Making Diabetes Electronic Medical Record Data Actionable: Promoting Benchmarking and Population Health Improvement Using the T1D Exchange Quality Improvement Portal.

This article describes how the T1D Exchange Quality Improvement Collaborative leverages an innovative web platform, the QI Portal, to gather and store electronic medical record (EMR) data to promote benchmarking and population health improvement in a type 1 diabetes learning health system. The authors explain the value of the QI Portal, the process for mapping center-level data from EMRs using standardized data specifications, and the QI Portal's unique features for advancing population health.

Inequities in Health Outcomes in Children and Adults With Type 1 Diabetes: Data From the T1D Exchange Quality Improvement Collaborative.

Health care inequities among racial and ethnic groups remain prevalent. For people with type 1 diabetes who require increased medical access and care, disparities are seen in access to care and health outcomes. This article reports on a study by the T1D Exchange Quality Improvement Collaborative evaluating differences in A1C, diabetic ketoacidosis (DKA), severe hypoglycemia, and technology use among racial and ethnic groups. In a diverse cohort of nearly 20,000 children and adults with type 1 diabetes, A1C was found to differ significantly among racial and ethnic groups. Non-Hispanic Blacks had higher rates of DKA and severe hypoglycemia and the lowest rate of technology use. These results underscore the crucial need to study and overcome the barriers that lead to inequities in the care and outcomes of people with type 1 diabetes.

The accuracy of self-reported blood pressure in the Medication adherence Improvement Support App For Engagement-Blood Pressure (MedISAFE-BP) trial: Implications for pragmatic trials.

Self-report of health conditions and behaviors is one potential strategy to increase the pace of enrollment into pragmatic clinical trials. In this study, we assessed the accuracy of self-reported poorly controlled hypertension among adults in the community who were screened for participation in the MedISAFE-BP trial. Of individuals who self-reported poorly controlled hypertension using the online trial enrollment platform, 64% had a systolic blood pressure less than 140 mm Hg when measured at home. Although we identified several characteristics associated with accurate self-report including older age (odds ratio [OR] 1.02 per year, 95% CI 1.01-1.03), diabetes (OR 1.59, 95% CI 1.17-2.14), and low health activation (OR 1.56 95% CI 1.17-2.07), we were unable to identify patients for whom self-reported hypertension would be a reliable method for their inclusion in a pragmatic trial.

Recombination in the human Pseudoautosomal region PAR1.

The pseudoautosomal region (PAR) is a short region of homology between the mammalian X and Y chromosomes, which has undergone rapid evolution. A crossover in the PAR is essential for the proper disjunction of X and Y chromosomes in male meiosis, and PAR deletion results in male sterility. This leads the human PAR with the obligatory crossover, PAR1, to having an exceptionally high male crossover rate, which is 17-fold higher than the genome-wide average. However, the mechanism by which this obligatory crossover occurs remains unknown, as does the fine-scale positioning of crossovers across this region. Recent research in mice has suggested that crossovers in PAR may be mediated independently of the protein PRDM9, which localises virtually all crossovers in the autosomes. To investigate recombination in this region, we construct the most fine-scale genetic map containing directly observed crossovers to date using African-American pedigrees. We leverage recombination rates inferred from the breakdown of linkage disequilibrium in human populations and investigate the signatures of DNA evolution due to recombination. Further, we identify direct PRDM9 binding sites using ChIP-seq in human cells. Using these independent lines of evidence, we show that, in contrast with mouse, PRDM9 does localise peaks of recombination in the human PAR1. We find that recombination is a far more rapid and intense driver of sequence evolution in PAR1 than it is on the autosomes. We also show that PAR1 hotspot activities differ significantly among human populations. Finally, we find evidence that PAR1 hotspot positions have changed between human and chimpanzee, with no evidence of sharing among the hottest hotspots. We anticipate that the genetic maps built and validated in this work will aid research on this vital and fascinating region of the genome.

Patient Demographics and Clinical Outcomes Among Type 1 Diabetes Patients Using Continuous Glucose Monitors: Data From T1D Exchange Real-World Observational Study.

BACKGROUND: The benefits of Continuous Glucose Monitoring (CGM) on glycemic management have been demonstrated in numerous studies; however, widespread uptake remians limited. The aim of this study was to provide real-world evidence of patient attributes and clinical outcomes associated with CGM use across clinics in the U.S. based T1D Exchange Quality Improvement (T1DX-QI) Collaborative. METHOD: We examined electronic Health Record data from eight endocrinology clinics participating in the T1DX-QI Collaborative during the years 2017-2019. RESULTS: Among 11,469 type 1 diabetes patients, 48% were CGM users. CGM use varied by race/ethnicity with Non-Hispanic Whites having higher rates of CGM use (50%) compared to Non-Hispanic Blacks (18%) or Hispanics (38%). Patients with private insurance were more likely to use CGM (57.2%) than those with public insurance (33.3%) including Medicaid or Medicare. CGM users had lower median HbA1c (7.7%) compared to nonusers (8.4%). Rates of diabetic ketoacidosis (DKA) and severe hypoglycemia were significantly higher in nonusers compared to CGM users. CONCLUSION: In this real-world study of patients in the T1DX-QI Collaborative, CGM users had better glycemic control and lower rates of DKA and severe hypoglycemia (SH) events, compared to nonusers; however, there were significant sociodemographic disparities in CGM use. Quality improvement and advocacy measures to promote widespread and equitable CGM uptake have the potential to improve clinical outcomes.

An Observational Crossover Study of People Using Real-Time Continuous Glucose Monitors Versus Self-Monitoring of Blood Glucose: Real-World Evidence Using EMR Data From More Than 12,000 People With Type 1 Diabetes.

BACKGROUND: We used real-world electronic health record (EHR) data to examine HbA1c levels among children and adults with type 1 diabetes (T1D) who are classified as continuous glucose monitor (CGM) users after T1D diagnosis and switch to self-monitoring of blood glucose (SMBG) during follow-up, versus people who opt for SMBG after T1D diagnosis and switch to CGM during follow-up visits. METHODS: We conducted an observational, case-crossover study using electronic medical record (EMR) data from the T1D Exchange Quality Improvement Collaborative. The primary outcome in this study was HbA1c. Baseline HbA1c levels were taken at the index date, corresponding to initial device classification, and compared with HbA1c value recorded at the clinic visit following device switch. RESULTS: Of all patients classified in the SMBG group, 7,706 switched to CGM use within the 5-year study time frame, and 5,123 of all initial CGM users switched to SMBG within the study time frame and were included in this analysis. At baseline, median (interquartile range [IQR]) HbA1c for SMBG use was 8.1 (2.4), whereas postcrossover to CGM use, there was a decline in median (IQR) levels to 7.7 (1.9) (P < .001). For baseline CGM users, median (IQR) HbA1c levels were 7.9 (2.0), and postcrossover to SMBG, median (IQR) HbA1c levels increased to 8.0 (2.9) (P < .001). CONCLUSION: We found that people who switched to CGM use had significantly improved HbA1c levels compared to those who switched to glucose monitoring with SMBG.

Transatlantic Comparison of Pediatric Continuous Glucose Monitoring Use in the Diabetes-Patienten-Verlaufsdokumentation Initiative and Type 1 Diabetes Exchange Quality Improvement Collaborative.

Achieving glycemic targets in youth and young adults with type 1 diabetes (T1D) is challenging. Diabetes devices, including continuous glucose monitors (CGM) may impact glycemic control. We analyzed the proportion of CGM use in youth and young adults with T1D at nine U.S. T1D Exchange Quality Improvement (T1DX-QI) Collaborative centers and 402 European diabetes prospective follow-up registry (Diabetes-Patienten-Verlaufsdokumentation [DPV]) sites from 2017 to 2020 and examined the association of CGM use to glycemic control as measured by hemoglobin A1c (HbA1c). CGM use increased each year from 2017 to 2020 across all age ranges (<6, 6-<12, 12-<18, 18-<25 years) in both registries and lower mean HbA1c was observed in CGM users compared with nonusers regardless of insulin delivery method for all years analyzed. CGM use appeared to increase more so in the European DPV than the U.S. T1DX-QI, which may be due to transatlantic differences in health care systems, insurance coverage, and prescriber habits.

Trends in Type 1 Diabetic Ketoacidosis During COVID-19 Surges at 7 US Centers: Highest Burden on non-Hispanic Black Patients.

CONTEXT: The impact of the COVID-19 pandemic on individuals with type 1 diabetes remains poorly defined. OBJECTIVE: We examined United States trends in diabetic ketoacidosis (DKA) among individuals with type 1 diabetes (T1D) during the COVID-19 pandemic at 7 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 Black (NHB) individuals experienced DKA in 2019 than non-Hispanic White (NHW) individuals (44.6% vs 16.0%; P < .001), and this disparity persisted during the COVID-19 pandemic (48.6% vs 18.6%; P < .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 < .001; insulin pump: 8.0% vs 10.6%, P < .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 < .001; surge 2: 6.6% vs 5.7%, P = .001). CONCLUSION: DKA frequency increased among T1D patients during COVID-19 surges with highest frequency among NHB patients. 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.

COVID-19 Hospitalization in Adults with Type 1 Diabetes: Results from the T1D Exchange Multicenter Surveillance Study.

CONTEXT: Diabetes mellitus is associated with increased COVID-19 morbidity and mortality, but there are few data focusing on outcomes in people with type 1 diabetes. OBJECTIVE: The objective of this study was to analyze characteristics of adults with type 1 diabetes for associations with COVID-19 hospitalization. DESIGN: An observational multisite cross-sectional study was performed. Diabetes care providers answered a 33-item questionnaire regarding demographics, symptoms, and diabetes- and COVID-19-related care and outcomes. Descriptive statistics were used to describe the study population, and multivariate logistic regression models were used to analyze the relationship between glycated hemoglobin (HbA1c), age, and comorbidities and hospitalization. SETTING: Cases were submitted from 52 US sites between March and August 2020. PATIENTS OR OTHER PARTICIPANTS: Adults over the age of 19 with type 1 diabetes and confirmed COVID-19 infection were included. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Hospitalization for COVID-19 infection. RESULTS: A total of 113 cases were analyzed. Fifty-eight patients were hospitalized, and 5 patients died. Patients who were hospitalized were more likely to be older, to identify as non-Hispanic Black, to use public insurance, or to have hypertension, and less likely to use continuous glucose monitoring or insulin pumps. Median HbA1c was 8.6% (70 mmol/mol) and was positively associated with hospitalization (odds ratio 1.42, 95% confidence interval 1.18-1.76), which persisted after adjustment for age, sex, race, and obesity. CONCLUSIONS: Baseline glycemic control and access to care are important modifiable risk factors which need to be addressed to optimize care of people with type 1 diabetes during the worldwide COVID-19 pandemic.

Inequities in Diabetic Ketoacidosis Among Patients With Type 1 Diabetes and COVID-19: Data From 52 US Clinical Centers.

OBJECTIVE: We examined whether diabetic ketoacidosis (DKA), a serious complication of type 1 diabetes (T1D) was more prevalent among Non-Hispanic (NH) Black and Hispanic patients with T1D and laboratory-confirmed coronavirus disease 2019 (COVID-19) compared with NH Whites. METHOD: This is a cross-sectional study of patients with T1D and laboratory-confirmed COVID-19 from 52 clinical sites in the United States, data were collected from April to August 2020. We examined the distribution of patient factors and DKA events across NH White, NH Black, and Hispanic race/ethnicity groups. Multivariable logistic regression analysis was performed to examine the odds of DKA among NH Black and Hispanic patients with T1D as compared with NH White patients, adjusting for potential confounders, such as age, sex, insurance, and last glycated hemoglobin A1c (HbA1c) level. RESULTS: We included 180 patients with T1D and laboratory-confirmed COVID-19 in the analysis. Forty-four percent (n = 79) were NH White, 31% (n = 55) NH Black, 26% (n = 46) Hispanic. NH Blacks and Hispanics had higher median HbA1c than Whites (%-points [IQR]: 11.7 [4.7], P < 0.001, and 9.7 [3.1] vs 8.3 [2.4], P = 0.01, respectively). We found that more NH Black and Hispanic presented with DKA compared to Whites (55% and 33% vs 13%, P < 0.001 and P = 0.008, respectively). After adjusting for potential confounders, NH Black patients continued to have greater odds of presenting with DKA compared with NH Whites (OR [95% CI]: 3.7 [1.4, 10.6]). CONCLUSION: We found that among T1D patients with COVID-19 infection, NH Black patients were more likely to present in DKA compared with NH White patients. Our findings demonstrate additional risk among NH Black patients with T1D and COVID-19.

Pregnancy phthalate metabolite concentrations and infant birth weight by gradations of maternal glucose tolerance.

BACKGROUND: Higher birth weight is an important adverse outcome associated with hyperglycemia in pregnancy. Recent studies suggest that phthalate exposure is associated with elevated glucose levels in pregnant women, with implications for higher birth weight in the offspring. No study to date has investigated the association between prenatal phthalate exposure on infant high birth weight accounting for the range of pregnancy glucose levels. METHODS: A total of 350 women participating in an ongoing pregnancy cohort had data available on urinary phthalate metabolite concentrations at up to four time points across pregnancy. Urinary phthalate metabolites were averaged across pregnancy and log-transformed, specific gravity-adjusted and analyzed in quartiles. Birth weight was examined continuously (in grams), as well as dichotomized as large for gestational age (>90th percentile). Glucose levels were assessed based on Results from 50-g glucose challenge tests as a part of screening for gestational diabetes conducted at 24-28 weeks gestation, and grouped into 3 categories <120 mg/dL, 120-<140 mg/dL and ≥140 mg/dL. Multivariable linear regression was performed, adjusting for potential confounders in the overall population and stratified by pregnancy glucose levels. RESULTS: Approximately 20% of infants born to women with glucose levels ≥140 mg/dL were large for gestational age. Average mono-ethyl phthalate (MEP) concentrations were higher among women who had glucose levels ≥140 mg/dL (geometric mean 140.9 µg/L; 95% CI: 91.6-216.8); however, higher MEP concentrations were not associated with higher birth weight. When stratified by maternal glucose levels, there was a suggestive association between higher concentrations of mono-(3-carboxypropyl) phthalate (MCPP) and higher birth weight among women with glucose levels ≥140 mg/dL (adj. birth weight: 569.2 g; 95% CI: 14.1, 1178.2). CONCLUSIONS: Higher urinary phthalate metabolite concentrations were not significantly associated with higher birth weight. Counter to our hypothesis, women with higher glucose levels and higher urinary phthalate metabolites did not deliver babies with higher birth weight.

Association of Periconception Paternal Body Mass Index With Persistent Changes in DNA Methylation of Offspring in Childhood.

Importance: While prenatal nutrition and maternal obesity are recognized as important contributors to epigenetic changes and childhood obesity, the role of paternal obesity in the epigenome of offspring has not been well studied. Objectives: To test whether periconception paternal body mass index (BMI) is associated with DNA methylation patterns in newborns, to examine associations between maternal and paternal BMI and the epigenome of offspring, and to examine persistence of epigenetic marks at ages 3 and 7 years. Design, Setting, and Participants: Project Viva is a prebirth cohort study of mothers and children including 2128 live births that enrolled mothers from April 1999 to July 2002 and followed offspring to adolescence. This study analyzed the subset of participants with available data on paternal BMI and DNA methylation in offspring blood in the newborn period, at age 3 years, and at age 7 years. Data were analyzed from July 2017 to October 2019. Exposures: The primary exposure was paternal periconception BMI; associations were adjusted for maternal prepregnancy BMI and stratified according to maternal BMI above or below 25. Main Outcomes and Measures: The primary outcome was genome-wide DNA methylation patterns in offspring blood collected at birth, age 3 years, and age 7 years. Results: A total of 429 father-mother-infant triads were included. The mean (SD) periconception paternal BMI was 26.4 (4.0) and mean maternal prepregnancy BMI was 24.5 (5.2); 268 fathers had BMI greater than or equal to 25 (mean [SD], 28.5 [3.3]) and 161 had BMI less than 25 (mean [SD], 22.8 [1.8]). Paternal BMI greater than or equal to 25 was associated with increased offspring birth weight compared with paternal BMI less than 25 (mean [SD] z score, 0.38 [0.91] vs 0.11 [0.96]; P = .004). Cord blood DNA methylation at 9 CpG sites was associated with paternal BMI independent of maternal BMI (q < .05). Methylation at cg04763273, between TFAP2C and BMP7, decreased by 5% in cord blood with every 1-unit increase in paternal BMI (P = 3.13 × 10-8); hypomethylation at this site persisted at ages 3 years and 7 years. Paternal BMI was associated with methylation at cg01029450 in the promoter region of the ARFGAP3 gene; methylation at this site was also associated with lower infant birth weight (ß = -0.0003; SD = 0.0001; P = .03) and with higher BMI z score at age 3 years. Conclusions and Relevance: In this study, paternal BMI was associated with DNA methylation, birth weight, and childhood BMI z score in offspring.