Coxsackievirus infection induces direct pancreatic ß cell killing but poor antiviral CD8+ T cell responses.

Coxsackievirus B (CVB) infection of pancreatic ß cells is associated with ß cell autoimmunity and type 1 diabetes. We investigated how CVB affects human ß cells and anti-CVB T cell responses. ß cells were efficiently infected by CVB in vitro, down-regulated human leukocyte antigen (HLA) class I, and presented few, selected HLA-bound viral peptides. Circulating CD8+ T cells from CVB-seropositive individuals recognized a fraction of these peptides; only another subfraction was targeted by effector/memory T cells that expressed exhaustion marker PD-1. T cells recognizing a CVB epitope cross-reacted with ß cell antigen GAD. Infected ß cells, which formed filopodia to propagate infection, were more efficiently killed by CVB than by CVB-reactive T cells. Our in vitro and ex vivo data highlight limited CD8+ T cell responses to CVB, supporting the rationale for CVB vaccination trials for type 1 diabetes prevention. CD8+ T cells recognizing structural and nonstructural CVB epitopes provide biomarkers to differentially follow response to infection and vaccination.

Type 1 Diabetes Screening and Diagnosis.

Those with concerning signs or symptoms should be evaluated for type 1 diabetes (T1D). Those with first-degree relatives with T1D or based on the presence of high-risk genes are at increased risk and benefit from screening. Universal screening should be considered in light of new potential therapies to delay disease progression. Although oral glucose tolerance test is the gold standard for T1D staging, there are multiple tools available when oral glucose tolerance test is not feasible. Risk score calculations increase the ability to predict disease progression. Testing should be repeated when symptoms of overt diabetes mellitus are not present.

Diabetes Care and Mental Health During the COVID-19 Pandemic: Perspectives of Adolescents with Diabetes, Parents, and Providers.

This study explored ways in which the COVID-19 pandemic impacted adolescents' diabetes management and psychosocial functioning, and how adolescents, parents, and providers viewed telemedicine. We present data from three studies: (1) a comparison of psychosocial functioning and glycemic levels before and after pandemic onset (n = 120 adolescents; 89% with type 1 diabetes), (2) an online survey of parents about pandemic-related stressors (n = 141), and (3) qualitative interviews with adolescents, parents, and medical providers about the pandemic's impacts on adolescents' diabetes care and mental health (n = 13 parent-adolescent dyads; 7 medical providers). Results suggested some adverse effects, including disrupting routines related to health behaviors and psychosocial functioning and impairing adolescents' quality of life. Despite these challenges, most participants did not endorse significant impacts. Some even noted benefits, such as increased parental supervision of diabetes management that can be leveraged beyond the pandemic. Furthermore, telemedicine offers benefits to continuity of diabetes care but presents challenges to care quality. These findings underscore the varied and unique impacts of the COVID-19 pandemic on adolescents with diabetes.

Current Practices in Operationalizing and Addressing Racial Equity in the Provision of Type 1 Diabetes Care: Insights from the Type 1 Diabetes Exchange Quality Improvement Collaborative Health Equity Advancement Lab.

OBJECTIVE: Medical racism contributes to adverse health outcomes. Type 1 Diabetes Exchange Quality Improvement Collaborative (T1DX-QI) is a large population-based cohort engaged in data sharing and quality improvement to drive system changes in T1D care. The annual T1DX-QI survey included questions to evaluate racial equity in diabetes care and practices to promote equity. METHODS: The annual T1DX-QI survey was administered to participating clinics in fall 2022 and had a 93% response rate. There were 50 responses (pediatric: 66% and adult: 34%). Questions, in part, evaluated clinical resources and racial equity. Response data were aggregated, summarized, and stratified by pediatric/adult institutions. RESULTS: Only 21% pediatric and 35% adult institutions felt that all their team members can articulate how medical racism contributes to adverse diabetes outcomes. Pediatric institutions reported more strategies to address medical racism than adult (3.6 vs 3.1). Organizational strategies to decrease racial discrimination included employee trainings, equity offices/committees, patient resources, and hiring practices. Patient resources included interpreter services, transportation, insurance navigation, and housing and food assistance. Hiring practices included changing prior protocols, hiring from the community, and diversifying workforces. Most institutions have offered antiracism training in the last year (pediatric: 85% and adult: 72%) and annually (pediatric: 64% and adult: 56%). Pediatric teams felt that their antiracism training was effective more often (pediatric: 60% and adult: 45%) and more commonly, they were provided resources (pediatric: 67% and adult: 47%) to help address inequities. CONCLUSION: Despite increased antiracism training, insufficient institutional support and perceived subeffective training still represent obstacles, especially in adult institutions. Sharing effective strategies to address medical racism will help institutions take steps to mitigate inequities.

Longitudinal Trends in Glycemic Outcomes and Technology Use for Over 48,000 People with Type 1 Diabetes (2016-2022) from the T1D Exchange Quality Improvement Collaborative.

Objective: Previous studies revealed that hemoglobin A1c (HbA1c) increased overall in the United States in the past decade. In addition, health inequities in type 1 diabetes (T1D) outcomes by race/ethnicity and insurance type persist. This study examines the trends in HbA1c from 2016 to 2022 stratified by race/ethnicity and insurance in a large multicenter national database. Research Design and Methods: We analyzed glycemic outcomes and diabetes device use trends for >48,000 people living with type 1 diabetes (PwT1D) from 3 adult and 12 pediatric centers in the T1D Exchange Quality Improvement Collaborative (T1DX-QI), comparing data from 2016 to 2017 with data from 2021 to 2022. Results: The mean HbA1c in 2021-2022 was lower at 8.4% compared with the mean HbA1c in 2016-2017 of 8.7% (0.3% improvement; P < 0.01). Over the same period, the percentage of PwT1D using a continuous glucose monitor (CGM), insulin pump, or hybrid closed-loop system increased (45%, 12%, and 33%, respectively). However, these improvements were not equitably demonstrated across racial/ethnic groups or insurance types. Racial/ethnic and insurance-based inequities persisted over all 7 years across all outcomes; comparing non-Hispanic White and non-Hispanic Black PwT1D, disparate gaps in HbA1c (1.2%-1.6%), CGM (30%), pump (25%-35%), and hybrid-closed loop system (up to 20%) are illuminated. Conclusion: Population-level data on outcomes, including HbA1c, can provide trends and insights into strategies to improve health for PwT1D. The T1DX-QI cohort showed a significant improvement in HbA1c from 2016 to 2022. Improvements in diabetes device use are also demonstrated. However, these increases were inconsistent across all racial/ethnic groups or insurance types, an important focus for future T1D population health improvement work.

Coxsackievirus infection induces direct pancreatic ß-cell killing but poor anti-viral CD8+ T-cell responses.

Coxsackievirus B (CVB) infection of pancreatic ß cells is associated with ß-cell autoimmunity. We investigated how CVB impacts human ß cells and anti-CVB T-cell responses. ß cells were efficiently infected by CVB in vitro, downregulated HLA Class I and presented few, selected HLA-bound viral peptides. Circulating CD8+ T cells from CVB-seropositive individuals recognized only a fraction of these peptides, and only another sub-fraction was targeted by effector/memory T cells that expressed the exhaustion marker PD-1. T cells recognizing a CVB epitope cross-reacted with the ß-cell antigen GAD. Infected ß cells, which formed filopodia to propagate infection, were more efficiently killed by CVB than by CVB-reactive T cells. Thus, our in-vitro and ex-vivo data highlight limited T-cell responses to CVB, supporting the rationale for CVB vaccination trials for type 1 diabetes prevention. CD8+ T cells recognizing structural and non-structural CVB epitopes provide biomarkers to differentially follow response to infection and vaccination.

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.

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.

Impact of diabetes status and related factors on COVID-19-associated hospitalization: A nationwide retrospective cohort study of 116,370 adults with SARS-CoV-2 infection.

AIMS: We examined diabetes status (no diabetes; type 1 diabetes [T1D]; type 2 diabetes [T2D]) and other demographic and clinical factors as correlates of coronavirus disease 2019 (COVID-19)-related hospitalization. Further, we evaluated predictors of COVID-19-related hospitalization in T1D and T2D. METHODS: We analyzed electronic health record data from the de-identified COVID-19 database (December 2019 through mid-September 2020; 87 US health systems). Logistic mixed models were used to examine predictors of hospitalization at index encounters associated with confirmed SARS-CoV-2 infection. RESULTS: In 116,370 adults (>=18 years old) with COVID-19 (93,098 no diabetes; 802 T1D; 22,470 T2D), factors that independently increased risk for hospitalization included diabetes, male sex, public health insurance, decreased body mass index (BMI; <25.0-29.9 kg/m2), increased BMI (>25.0-29.9 kg/m2), vitamin D deficiency/insufficiency, and Elixhauser comorbidity score. After further adjustment for concurrent hyperglycemia and acidosis in those with diabetes, hospitalization risk was substantially higher in T1D than T2D and in those with low vitamin D and elevated hemoglobin A1c (HbA1c). CONCLUSIONS: The higher hospitalization risk in T1D versus T2D warrants further investigation. Modifiable risk factors such as vitamin D deficiency/insufficiency, BMI, and elevated HbA1c may serve as prognostic indicators for COVID-19-related hospitalization in adults with diabetes.

Videoconference based training on diabetes technology for school nurses and staff: Pilot study.

PURPOSE: Children with diabetes spend a significant portion of time at school and in school-related activities and rely on school nurses for diabetes management support. Diabetes technologies are rapidly evolving, and there are no standardized competencies or training programs for school personnel providing diabetes care. DESIGN AND METHODS: A virtual diabetes education program was provided to school nurses and staff in 3 Florida school districts. Program feasibility was measured by attendance; acceptability was measured with a usability survey; and efficacy was measured by participants' improvements in scores on pre- and post-training knowledge assessments. Descriptive statistics were generated and improvements in knowledge were evaluated via t-test. P-values <0.05 were considered significant. RESULTS: Pilot survey data (n = 91) revealed high demand for diabetes technology and basic management education among school nurses and staff. Eighty-eight school personnel from 64 schools attended the training, with 67 participants completing the demographic survey and at least one of the pre- and post-training assessments. Post-test scores demonstrated mean + 10.6% absolute improvement on the diabetes technology subscale, +11.5% on the basic management subscale, and + 10.9% on the ketone management subscale, all p < 0.001. Fifty-three participants completed the usability survey with 92% reporting they benefitted from training. CONCLUSIONS: Virtual training is feasible and acceptable for delivering diabetes technology education to large numbers of school personnel. Study results demonstrate improved diabetes knowledge. PRACTICE IMPLICATIONS: Establishing a standardized training program on diabetes technology for school personnel can optimize diabetes care in the school setting.

Psychosocial screening in a pediatric diabetes clinic: Adolescents' and mothers' perspectives.

OBJECTIVE: Adolescents with type 1 diabetes (T1D) frequently experience psychosocial concerns, and mental health screening is becoming increasingly common in routine diabetes care. However, little is known about what adolescents or their caregivers think about the role of mental health screening and intervention within the context of comprehensive diabetes care, or how their diabetes care providers should be involved in navigating mental health concerns. This study used qualitative methods to obtain the perspectives of adolescents with T1D and their caregivers regarding these issues. METHODS: Participants were 13 adolescents with T1D (ages 12-19 years; M = 15.1 years; 53.8% female; 61.5% Hispanic/Latinx White) and 13 mothers, recruited from an outpatient pediatric endocrinology clinic in South Florida, who participated in semi-structured interviews via video teleconference. Thematic content analysis was used to evaluate participants' responses. RESULTS: Adolescents and their mothers reported positive experiences with the clinic's psychosocial screening procedures and appreciated meeting with the psychology team during visits. They wanted the clinic to offer more opportunities for peer support. Mothers highlighted barriers to seeking mental health care outside of the clinic and the importance of mental health professionals understanding diabetes. Mothers also wanted the clinic to offer more on-site therapeutic services. DISCUSSION: Study participants valued psychosocial screening and supported addressing mental health as a routine part of diabetes comprehensive care.

Transitioning to Telehealth Services in a Pediatric Diabetes Clinic During COVID-19: An Interdisciplinary Quality Improvement Initiative.

COVID-19 necessitated a rapid shift to telehealth for psychologists offering consultation-liaison services in pediatric medical settings. However, little is known about how psychologists providing these services adapted to using telehealth service delivery formats. This report details how our interdisciplinary team identified declining psychosocial screener completion and psychology consultation rates as primary challenges following a shift to telehealth within a pediatric diabetes clinic. We utilized the Plan-Do-Study-Act (PDSA) quality improvement framework to improve screening and consultation rates, which initially declined during the telehealth transition. Screening and consultation rates dropped initially, but recovered to nearly pre-pandemic levels following three PDSA intervention cycles. During implementation, challenges arose related to the feasibility of patient interactions, interdisciplinary collaboration, patient engagement, and ethical issues. Clinics shifting psychology consultation-liaison services to telehealth should prioritize interdisciplinary communication, elicit perspectives from all clinic professionals, leverage the electronic health record, and develop procedures for warm handoffs and navigating ethical issues.

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.

Severe Diabetic Ketoacidosis in a Child with Type-1 Diabetes, Asthma, and COVID-19.

Little is known about the association between novel coronavirus disease 2019 (COVID-19) and type-1 diabetes in children. A 16-year-old female patient with history of type-1 diabetes was admitted for life threatening diabetic ketoacidosis (DKA). She recovered from the DKA after 24 hours of insulin infusion and rehydration. On day 2, she was diagnosed with COVID-19. The DKA relapsed and required restarting insulin. She developed leukopenia, neutropenia, and high ferritin. Upon recovery, she was discharged for self-quarantine. Severity of DKA in children with COVID-19 is multifactorial. Clinical suspicion of COVID should be heightened in patients who present with unexplainedly severe DKA.

Sedentary behavior moderates the relationship between physical activity and cardiometabolic risk in young Latino children.

This study investigated the role of objectively measured moderate-vigorous physical activity (MVPA) and sedentary behavior on cardiometabolic risk factors of young Latino children. We hypothesized that MVPA would be associated with lower cardiometabolic risk when sedentary behavior is low. We studied 86 primarily low-income, Latino children using a cross-sectional study design. The study sample consisted of 51 girls and 35 boys, with mean age 5.6 (SD = .53) years. Physical activity was measured by accelerometry, anthropometric measures obtained, and fasting blood samples were used to measure cardiometabolic risk factors. Greater levels of sedentary behavior were associated with increased waist circumference (rs = .24, p < .05) and metabolic risks. MVPA, however, had significant beneficial associations with all cardiometabolic risk factors (rs-range = -.20 to -.45, p < .05) with the exception of plasma insulin. MVPA predicted latent variables representing anthropometric risk (ß = -.57, p < .01), cardiac risk (ß = -.74, p < .01), and metabolic risk (ß = -.88, p < .01). Sedentary behavior significantly moderated the effect of MVPA on anthropometric (ß-interaction = .49, p < .01), cardiac (ß-interaction = .45, p < .01), and metabolic risk (ß-interaction = .77, p < .01), such that more MVPA was associated with better health outcomes under conditions of lower sedentary behavior. The model explained 13%, 22%, and 45% variance in anthropometric, cardiac, and metabolic risk factors, respectively. Increased MVPA is associated with decreased cardiometabolic risk in young Latino children, particularly when sedentary behavior is low.

This study investigated the role of objectively measured moderate­vigorous physical activity (MVPA) and sedentary behavior on cardiometabolic risk factors of young Latino children. We hypothesized that MVPA would be associated with lower cardiometabolic risk when sedentary behavior is low. The study sample consisted of 51 girls and 35 boys, with mean age 5.6 (SD = .53) years. Participants were primarily low-income, Latino children. We found that greater levels of sedentary behavior were associated with increased waist circumference and metabolic risks. MVPA, however, had significant beneficial associations with all cardiometabolic risk factors with the exception of insulin. MVPA predicted latent variables representing anthropometric risk, cardiac risk, and metabolic risk. Sedentary behavior significantly moderated the effect of MVPA on anthropometric, cardiac, and metabolic risk, such that more MVPA was associated with better health outcomes under conditions of lower sedentary behavior. We conclude that an increased MVPA is associated with decreased cardiometabolic risk in young Latino children, particularly when sedentary behavior is low.

Diabetic ketoacidosis drives COVID-19 related hospitalizations in children with type 1 diabetes.

BACKGROUND: Diabetes is a risk factor for poor COVID-19 outcomes, but pediatric patients with type 1 diabetes are poorly represented in current studies. METHODS: T1D Exchange coordinated a US type 1 diabetes COVID-19 registry. Forty-six diabetes centers submitted pediatric cases for patients with laboratory confirmed COVID-19. Associations between clinical factors and hospitalization were tested with Fisher's Exact Test. Logistic regression was used to calculate odds ratios for hospitalization. RESULTS: Data from 266 patients with previously established type 1 diabetes aged <19 years with COVID-19 were reported. Diabetic ketoacidosis (DKA) was the most common adverse outcome (n = 44, 72% of hospitalized patients). There were four hospitalizations for severe hypoglycemia, three hospitalizations requiring respiratory support (one of whom was intubated and mechanically ventilated), one case of multisystem inflammatory syndrome in children, and 10 patients who were hospitalized for reasons unrelated to COVID-19 or diabetes. Hospitalized patients (n = 61) were more likely than nonhospitalized patients (n = 205) to have minority race/ethnicity (67% vs 39%, P < 0.001), public insurance (64% vs 41%, P < 0.001), higher A1c (11% [97 mmol/mol] vs 8.2% [66 mmol/mol], P < 0.001), and lower insulin pump and lower continuous glucose monitoring use (26% vs 54%, P < 0.001; 39% vs 75%, P < 0.001). Age and gender were not associated with risk of hospitalization. Higher A1c was significantly associated with hospitalization, with an odds ratio of 1.56 (1.34-1.84) after adjusting for age, gender, insurance, and race/ethnicity. CONCLUSIONS: Higher A1c remained the only predictor for hospitalization with COVID-19. Diabetic ketoacidosis is the primary concern among this group.

Comprehensive psychosocial screening in a pediatric diabetes clinic.

OBJECTIVE: The ISPAD recommends routine, comprehensive psychosocial screening for adolescents with diabetes. However, few clinics have implemented procedures consistent with these guidelines. This study describes the results of a universal, comprehensive psychosocial screening program in an integrated pediatric diabetes clinic located within an academic medical center. RESEARCH DESIGN AND METHODS: Participants included 232 ethnically diverse adolescents with type 1 diabetes (55.5% female; M age = 14.85; 58.5% Hispanic; 20% Black). Adolescents completed screening measures on iPads in the waiting room before their medical visit. The proportion of adolescents screening positive on each psychosocial measure was assessed, and regression analyses evaluated how psychosocial variables accounted for variance in insulin non-adherence and glycemic control (measured by A1c). RESULTS: Psychosocial concerns were common and ranged from 7% of adolescents screening positive for disordered eating and suicide risk to 52% screening positive for low motivation to manage diabetes. A1c and insulin non-adherence were positively correlated with suicide risk, depressive symptoms, anxiety, disordered eating, diabetes stress, blood glucose monitoring stress, family conflict, and total number of elevations, and negatively correlated with intrinsic motivation. Insulin non-adherence, disordered eating, diabetes stress, and family conflict uniquely predicted A1c. Age, motivation, and family conflict uniquely predicted insulin non-adherence. Eighty-three percent of eligible youth completed the screener. Referrals by physicians to the team psychologist increased by 25% after the screening program was implemented. CONCLUSIONS: Comprehensive psychosocial screening can be effectively implemented as part of routine pediatric diabetes care and can identify adolescents in need of additional supports.

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.

Long-term Follow-up of Glycemic and Neurological Outcomes in an International Series of Patients With Sulfonylurea-Treated ABCC8 Permanent Neonatal Diabetes.

OBJECTIVE: ABCC8 mutations cause neonatal diabetes mellitus that can be transient (TNDM) or, less commonly, permanent (PNDM); ∼90% of individuals can be treated with oral sulfonylureas instead of insulin. Previous studies suggested that people with ABCC8-PNDM require lower sulfonylurea doses and have milder neurological features than those with KCNJ11-PNDM. However, these studies were short-term and included combinations of ABCC8-PNDM and ABCC8-TNDM. We aimed to assess the long-term glycemic and neurological outcomes in sulfonylurea-treated ABCC8-PNDM. RESEARCH DESIGN AND METHODS: We studied all 24 individuals with ABCC8-PNDM diagnosed in the U.K., Italy, France, and U.S. known to transfer from insulin to sulfonylureas before May 2010. Data on glycemic control, sulfonylurea dose, adverse effects including hypoglycemia, and neurological features were analyzed using nonparametric statistical methods. RESULTS: Long-term data were obtained for 21 of 24 individuals (median follow-up 10.0 [range 4.1-13.2] years). Eighteen of 21 remained on sulfonylureas without insulin at the most recent follow-up. Glycemic control improved on sulfonylureas (presulfonylurea vs. 1-year posttransfer HbA1c 7.2% vs. 5.7%, P = 0.0004) and remained excellent long-term (1-year vs. 10-year HbA1c 5.7% vs. 6.5%, P = 0.04), n = 16. Relatively high doses were used (1-year vs. 10-year dose 0.37 vs. 0.25 mg/kg/day glyburide, P = 0.50) without any severe hypoglycemia. Neurological features were reported in 13 of 21 individuals; these improved following sulfonylurea transfer in 7 of 13. The most common features were learning difficulties (52%), developmental delay (48%), and attention deficit hyperactivity disorder (38%). CONCLUSIONS: Sulfonylurea treatment of ABCC8-PNDM results in excellent long-term glycemic control. Overt neurological features frequently occur and may improve with sulfonylureas, supporting early, rapid genetic testing to guide appropriate treatment and neurodevelopmental assessment.

EARLY ONSET OF MODY5 DUE TO HAPLOINSUFFICIENCY OF HNF1B.

OBJECTIVE: To report 2 patients with haploinsufficiency of hepatic nuclear factor 1 homeobox B (HNF1B) that results in the onset of maturity onset diabetes of the young type 5 (MODY5) before 3 years of age. METHODS: We present 2 unusual patients with MODY5 that was diagnosed at 33 and 22 months of age, respectively. We describe the presentations, clinical course, and genetic tests of both patients, and lastly, we review the literature on the prevalence and the age of presentation of MODY5 both in children and in adult patients. RESULTS: The first patient had severe congenital renal dysplasia, and deoxyribonucleic acid microarray indicated the deletion of 17q12. Hemoglobin A1c (HbA1c) was obtained due to the concern of MODY5, and the initial level (6.6%, 49 mmol/mol) was abnormally elevated. The second patient had mild renal dysplasia and 17q12 deletion encompassing the HNF1B gene. Hyperglycemia was identified during an episode of respiratory illness. HbA1c (6.2%, 44 mmol/mol) level was abnormally elevated. Pancreatic autoantibodies were absent in both patients. Diet modification resulted in an improvement of HbA1c in both patients. CONCLUSION: Our report highlights the importance of considering MODY5 in patients with congenital anomalies of kidney. Identification of children with MODY5 permits early management of hyperglycemia.