Hybrid Closed Loop Systems Improve Glycemic Control and Quality of Life in Historically Minoritized Youth with Diabetes.

Background: We assessed changes in glycemic control and person-reported outcome measures (PROMs) with t:slim X2 insulin pump with Control-IQ technology use among historically minoritized youth who are least likely to access hybrid closed loop (HCL) technology. Methods: This single-arm, prospective pilot study enrolled 15 publicly insured, insulin pump-naïve, non-Hispanic Black youth ages 6 to <21 years with type 1 diabetes and hemoglobin A1c (HbA1c) ≥10% in a 6-month study of HCL use. The primary outcome was absolute change in time in range (TIR) (70-180 mg/dL). Secondary outcomes included other continuous glucose monitor metrics, PROMs, and diabetic ketoacidosis (DKA) incidence. Results: For 13 youth (median 14.8 years, 53.3% female, HbA1c 11.7%) who completed the study, baseline TIR of 12.3% (6.3-27.1%) increased 23.7%-points (16.9, 30.5%; P < 0.001) or 5.7 h per day. Percent time >250 mg/dL decreased 33.9%-points (-44.8, -23.1%; P < 0.001) or 8.1 h per day from a baseline of 69.4% (51.6, 84.0%). Median time in HCL was 78.3% (59.7, 87.3%). Youth received 10.1 (9.2, 11.9) boluses per day, 71.7% (63.8, 79.3%) of which were HCL-initiated autoboluses. Diabetes-specific quality of life increased among parents (P < 0.001) and youth (P = 0.004), and diabetes distress decreased in both groups (P < 0.001, P = 0.005). Improvements in glycemia did not correlate with any baseline youth or parent PROMs. DKA was high at baseline (67 episodes/100-person years) and did not increase during the intervention (72 episodes/100-person years, P = 0.78). Conclusion: Improvements in glycemic control and quality of life exceeding pivotal trial findings without increased safety risks among historically minoritized youth emphasize the need for equitable access to HCL systems. ClinicalTrials.gov: clinicaltrials.gov ID (NCT04807374).

Case Report: Insulin hypersensitivity in youth with type 1 diabetes.

Objective: Immediate type I, type III, and delayed type IV hypersensitivity reactions to insulin are rare, but potentially serious complications of exogenous insulin administration required for the treatment of type 1 diabetes (T1D). Methods: We present four cases of insulin hypersensitivity reactions occurring in youth with T1D and a literature review of this topic. Results: Insulin hypersensitivity reactions included types I, III, and IV with presentations ranging from localized urticaria, erythematous nodules, and eczematous plaques to anaphylaxis with respiratory distress. Reactions occurred in youth with newly diagnosed T1D and in those with long-standing T1D who were using both injection and insulin pump therapy. Multidisciplinary care involving pediatric endocrinology and allergy/immunology utilizing trials of many adjunct therapies yielded minimal improvement. Despite the use of various treatments, including antihistamines, topical therapies, immunosuppressant medications, desensitization trials, and intravenous immune globulin, cutaneous reactions, elevated hemoglobin A1c levels, and negative effects on quality of life remain persistent challenges. One patient became one of the youngest pancreas transplant recipients in the world at age 12 years due to uncontrollable symptoms and intolerable adverse effects of attempted therapies. Conclusion: Although rare, insulin hypersensitivity reactions negatively affect glycemic control and quality of life. These cases demonstrate the varying severity and presentation of insulin hypersensitivity reactions along with the limited success of various treatment approaches. Given the life-sustaining nature of insulin therapy, further studies are needed to better understand the underlying pathophysiology of insulin hypersensitivity and to develop targeted treatment approaches.

Real-World Glycemic Outcomes with Early Omnipod 5 Use in Youth with Type 1 Diabetes.

Background: Pivotal trials of diabetes technologies have demonstrated glycemic improvements; however, these trials include patients of limited diversity and ranges of glycemic control. We assessed changes in glycemic control during the first 90 days of Omnipod 5 use in a real-world cohort of youth with type 1 diabetes (T1D). Methods: Youth 2-21 years with T1D initiating Omnipod 5 at two pediatric academic centers were included. Fourteen days of baseline (BL) continuous glucose monitoring (CGM) data were compared against data from the first 90 days of Omnipod 5 use. Outcome measures included changes in time in range (TIR), hemoglobin A1c (HbA1c), and CGM and insulin pump metrics based on the duration of Omnipod 5 use. Results: Among 195 youth (78.9% non-Hispanic White, 15.4% publicly insured, age 11.7 years, T1D duration 3.3 years) TIR increased 11%-points, from 49% to 61% (P < 0.001), and HbA1c decreased 0.5%-points, from 7.5% to 6.9% (P < 0.001). TIR improved within the first 9 days of Omnipod 5 use (p < 0.001) and did not change significantly thereafter (P = 0.1) despite decreases in user-initiated boluses (5.1 vs. 5.0, P = 0.01) and carbohydrate entries (4.2 vs. 4.1, P = 0.005) from days 1-9 to days 1-90. TIR improved 15%-points among youth with BL TIR <60% compared to a 5%-point increase for youth with BL TIR ≥60% (P < 0.001). Conclusions: Glycemic control improved within 9 days of Omnipod 5 initiation in this real-world cohort, and improvements were sustained over the first 90 days of use despite concomitant decreases in user-initiated boluses. These improvements were comparable to those observed in the pivotal trial.

Virtual Learning and Youth-Onset Type 2 Diabetes During the COVID-19 Pandemic.

INTRODUCTION: Cases and severity of presentation of youth-onset type 2 diabetes (Y-T2D) increased during the COVID-19 pandemic, yet the potential drivers of this rise remain unknown. During this time public health mandates paused in-person education and limited social interactions, resulting in radical lifestyle changes. We hypothesized that the incidence and severity of presentation of Y-T2D increased during virtual learning amidst the COVID-19 pandemic. MATERIALS AND METHODS: We conducted a single center retrospective chart review to identify all newly diagnosed cases of Y-T2D (n=387) at a pediatric tertiary care center in Washington, DC during three pre-determined learning periods as defined by learning modality in Washington, DC Public Schools: pre-pandemic in-person learning (3/11/2018-3/13/2020), pandemic virtual learning (3/14/2020-8/29/2021), and pandemic in-person learning (8/30/2021-3/10/2022) periods. RESULTS: Incident cases were stable during pre-pandemic in-person learning (3.9 cases/month, 95% CI: 2.8 - 5.4 cases/month), increased to a peak during virtual learning (18.7 cases/month, 95% CI: 15.9 - 22.1 cases/month), and declined with return to in-person learning (4.3 cases/month, 95% CI: 2.8 - 6.8 cases/month). Y-T2D incidence was 16.9 (95% CI: 9.8-29.1, p<0.001) and 5.1-fold higher (95% CI: 2.9-9.1, p<0.001) among non-Hispanic Black and Latinx youth, respectively, throughout the study period. Overall COVID-19 infection rates at diagnosis were low (2.5%) and were not associated with diabetes incidence (p=0.26). DISCUSSION/CONCLUSIONS: This study provides timely insights into an important and modifiable correlate of Y-T2D incidence, its disproportionate impact on underserved communities, and the need to consider the effects on long-term health outcomes and pre-existing healthcare inequities when designing public policy.

Differences in positive expectancy of hybrid closed loop (HCL) insulin delivery systems do not explain racial differences in HCL use.

Aims: Hybrid closed loop (HCL) insulin delivery systems improve glycemia and quality of life among youth with type 1 diabetes (T1D), however there are inequities in use. We aimed to evaluate whether differences in positive expectancy of HCL systems may explain differences in use. Methods: Fifteen publicly-insured, non-Hispanic Black (NHB) youth with hemoglobin A1C (HbA1c) ≥ 10% enrolled in a study exploring changes in glycemia and person reported outcomes (PRO) during 6 months of Tandem t:slim X2 insulin pump with Control-IQ technology. At baseline youth and parents completed PROs, including Insulin Delivery Systems: Perceptions, Ideas, Reflections and Expectations (INSPIRE) survey assessing positive expectancy of HCL use, and Problem Areas in Diabetes (PAID) survey assessing diabetes-related distress. Differences between this cohort and the Tandem Control-IQ pediatric pivotal trial (DCLP5) cohort were assessed. Results: As compared to the DCLP5 cohort (0% NHB, 10% publicly-insured), baseline glycemic indicators were suboptimal (MHbA1c 11.9 ± 1.4% vs 7.6 ± 0.9%, p < 0.0001; continuous glucose monitor (CGM) time-above-range > 180 mg/dL 82 ± 15% vs 45 ± 18%, p < 0.0001). INSPIRE scores in both cohorts were equally high among youth (80 ± 10 vs 77 ± 13, p = 0.41) and parents (88 ± 14 vs 85 ± 11, p = 0.37). PAID scores were higher among parents (68 ± 19 vs 43 ± 16, p < 0.0001), but not youth (43 ± 16 vs 35 ± 16, p = 0.09) in the historically marginalized cohort as compared to the DCLP5 cohort. Conclusions: Despite differences in glycemic control and diabetes related burden, positive expectancy of HCL systems is comparable among historically marginalized youth with T1D and the predominantly non-Hispanic White, privately insured DCLP5 cohort. These findings suggest that differences in perceptions of HCL technology may not explain inequities in use.

Applying the use of shared medical appointments (SMAs) to improve continuous glucose monitor (CGM) use, glycemic control, and quality of life in marginalized youth with type 1 diabetes: Study protocol for a pilot prospective cohort study.

Background: Continuous glucose monitors (CGMs) have been associated with improved glycemic control and diabetes-related quality of life in youth with type 1 diabetes (T1D), however use is lowest among youth from low-income households and racial/ethnic minorities. Shared medical appointments (SMAs) have been shown to improve glycemic control and reduce diabetes distress in adolescents with T1D, but a focus on marginalized youth has been lacking. This prospective cohort pilot study will assess feasibility and acceptability of the SMA intervention and impact on CGM uptake and sustained use, glycemic control, and diabetes distress in marginalized youth with elevated hemoglobin A1c (HbA1C). Methods: The pilot study will recruit 20 publicly insured youth with T1D aged 8-12 years who identify as non-Hispanic Black or Latinx and have had at least one HbA1C value > 8% in the past year and their primary caretaker. The trial will employ an enrollment visit, SMA visits every 3 months over a 12-month study period, and a 6-month follow-up observational period. Feasibility measures include proportion of eligible youth successfully recruited for participation, proportion initiating CGM, SMA attendance, and retention through study completion. Acceptability will be assessed using satisfaction surveys. Changes in glycemic control will be assessed using CGM metrics and A1c from baseline to completion of the 12-month SMA intervention, as well as 3 and 6-months after completion of the SMA intervention. Conclusion: Implementing SMAs for marginalized youth has the potential to address diabetes disparities by optimizing clinical and psychosocial outcomes for the most vulnerable youth living with T1D.Trial Registration: https://clinicaltrials.gov/ct2/show/NCT05431686.

Endocrine Complications of Cystic Fibrosis.

Endocrine comorbidities have become increasingly important medical considerations as improving cystic fibrosis (CF) care increases life expectancy. Although the underlying pathophysiology of CF-related diabetes remains elusive, the use of novel technologies and therapeutics seeks to improve both CF-related outcomes and quality of life. Improvements in the overall health of those with CF have tempered concerns about pubertal delay and short stature; however, other comorbidities such as hypogonadism and bone disease are increasingly recognized. Following the introduction of highly effective modulator therapies there are many lessons to be learned about their long-term impact on endocrine comorbidities.

The Coronavirus Disease 2019 Pandemic is Associated with a Substantial Rise in Frequency and Severity of Presentation of Youth-Onset Type 2 Diabetes.

OBJECTIVES: To evaluate the frequency and severity of new cases of youth-onset type 2 diabetes in the US during the first year of the pandemic compared with the mean of the previous 2 years. STUDY DESIGN: Multicenter (n = 24 centers), hospital-based, retrospective chart review. Youth aged ≤21 years with newly diagnosed type 2 diabetes between March 2018 and February 2021, body mass index ≥85th percentile, and negative pancreatic autoantibodies were included. Demographic and clinical data, including case numbers and frequency of metabolic decompensation, were compared between groups. RESULTS: A total of 3113 youth (mean [SD] 14.4 [2.4] years, 50.5% female, 40.4% Hispanic, 32.7% Black, 14.5% non-Hispanic White) were assessed. New cases of type 2 diabetes increased by 77.2% in the year during the pandemic (n = 1463) compared with the mean of the previous 2 years, 2019 (n = 886) and 2018 (n = 765). The likelihood of presenting with metabolic decompensation and severe diabetic ketoacidosis also increased significantly during the pandemic. CONCLUSIONS: The burden of newly diagnosed youth-onset type 2 diabetes increased significantly during the coronavirus disease 2019 pandemic, resulting in enormous strain on pediatric diabetes health care providers, patients, and families. Whether the increase was caused by coronavirus disease 2019 infection, or just associated with environmental changes and stressors during the pandemic is unclear. Further studies are needed to determine whether this rise is limited to the US and whether it will persist over time.

Monitoring of paediatric type 1 diabetes.

PURPOSE OF REVIEW: This article reviews recent developments in methods used to monitor paediatric type 1 diabetes (T1D), including an examination of the role of glycated haemoglobin (haemoglobin A1c) and its limitations for long-term assessment of glycaemia in individual patients, self-monitoring of blood glucose, continuous glucose monitoring (CGM) systems and ketone monitoring. RECENT FINDINGS: Monitoring of glycemia and ketones, when indicated, is a cornerstone of paediatric T1D management and is essential to optimize glycaemic control. Ongoing technological advancements have led to rapid changes and considerable improvement in the methods used to monitor glucose concentrations in people with T1D. As a result of recent innovations that have enhanced accuracy and usability, CGM is now considered the optimal method for monitoring glucose concentrations and should be introduced soon after diagnosis of T1D. SUMMARY: Patients/families and healthcare providers must receive comprehensive education and proper training in the use of CGM and interpretation of the vast amounts of data. Future challenges include ensuring equal access to and optimizing clinical use of CGM to further improve T1D care and outcomes.

Correlates and Patterns of COVID-19 Vaccination Intentions among Parents of Children with Type 1 Diabetes.

OBJECTIVE: To examine psychosocial, sociodemographic, medical, and coronavirus disease 2019 (COVID-19) experiences as correlates of COVID-19 vaccination intentions among parents of children with type 1 diabetes (T1D). METHODS: 121 parents of children with T1D (Mchild age = 7.78 ± 1.70; MA1c = 8.3% ± 1.5%) in the mid-Atlantic and Southwest regions completed self-report measures in February to March 2021. RESULTS: Parents' general vaccination behaviors and attitudes were associated with COVID-19 vaccination intentions. Child insurance type and social distancing adherence were associated with vaccination intention in the Southwest site. Higher A1c was associated with lower intention. Vaccine safety was the top reported concern. CONCLUSIONS: COVID-19 vaccination intentions are important to address in parents of youth with health conditions.

Baseline Quality Improvement Capacity of 33 Endocrinology Centers Participating in the T1D Exchange Quality Improvement Collaborative.

This article describes the evolution of the Type 1 Diabetes Exchange Quality Improvement Collaborative (T1DX-QI) and provides insight into the development and growth of a successful type 1 diabetes quality improvement (QI) program. Since its inception 8 years ago, the collaborative has expanded to include centers across the United States with varying levels of QI experience, while simultaneously achieving many tangible improvements in type 1 diabetes care. These successes underscore the importance of learning health systems, data-sharing, benchmarking, and peer collaboration as drivers for continuous QI. Future efforts will include recruiting additional small- to medium-sized centers focused on adult care and underserved communities to further the goal of improving care and outcomes for all people living with type 1 diabetes.

Practical aspects of diabetes technology use: Continuous glucose monitors, insulin pumps, and automated insulin delivery systems.

There have been tremendous advances in diabetes technology in the last decade. Continuous glucose monitors (CGM), insulin pumps, and automated insulin delivery (AID) systems aim to improve glycemic control while simultaneously decreasing the burden of diabetes management. Although diabetes technologies have been shown to decrease both hypoglycemia and hyperglycemia and to improve health-related quality of life in individuals with type 1 diabetes, the impact of these devices in individuals with cystic fibrosis-related diabetes (CFRD) is less clear. There are unique aspects of CFRD, including the different underlying pathophysiology and unique lived health care experience and comorbidities, that likely affect the use, efficacy, and uptake of diabetes technology in this population. Small studies suggest that CGM is accurate and may be helpful in guiding insulin therapy for individuals with CFRD. Insulin pump use has been linked to improvements in lean body mass and hemoglobin A1c among adults with CFRD. A recent pilot study highlighted the promise of AID systems in this population. This article provides an overview of practical aspects of diabetes technology use and device limitations that clinicians must be aware of in caring for individuals with CF and CFRD. Cost and limited insurance coverage remain significant barriers to wider implementation of diabetes technology use among patients with CFRD. Future studies exploring strategies to improve patient and CF provider education about these devices and studies showing the effectiveness of these technologies on health and patient-reported outcomes may lead to improved insurance coverage and increased rates of uptake and sustained use of these technologies in the CFRD community.

Cystic fibrosis-related diabetes: The patient perspective.

Cystic fibrosis-related diabetes (CFRD) affects nearly 20% of adolescents and 40-50% of adults. However, the impact on patients and their families is poorly understood. Here, we examine how patients perceive CFRD and identify gaps in our understanding of the patient experience. Despite its relatively high prevalence, data suggest that many individuals are not aware of the possibility of developing CFRD or compare it to other types of diabetes. Annual oral glucose tolerance testing (OGTT) may serve as an opportunity to provide education and prepare individuals for the possibility of developing abnormalities in glucose tolerance. Many cite lack of awareness of CFRD as the most difficult part of the diagnosis. While factors such as older age and a strong support system promote acceptance, most individuals view the diagnosis negatively and struggle to balance the demands of diabetes with other obligations, including airway clearance, nebulizer therapies, supplementation nutrition, and administration of vitamins and medications. Relatively few people with CFRD monitor their blood glucoses consistently, which is attributed to time constraints or an attempt to avoid pain. In addition, many feel that they are not prone to hypoglycemia and are not concerned with long-term complications, anticipating that they will succumb to their pulmonary disease before these become problematic. The adolescent period presents unique challenges for adherence as children work to develop autonomy. Factors that promote CFRD adherence include incorporating management into daily CF routines and the support of knowledgeable providers to help develop an individualized approach to management. Diabetes technology has the potential to reduce treatment burden and improve glycemic control, but data in CFRD are limited, and additional study is needed. Given that CFRD is associated with a decline in health-related quality of life, it is critical that providers understand patients' perspectives and address gaps in understanding and barriers to management.

Spontaneous and iatrogenic hypoglycemia in cystic fibrosis.

Spontaneous episodes of hypoglycemia can occur in people with cystic fibrosis (CF) without diabetes, who are not on glucose lowering medications. Spontaneous hypoglycemia in CF could occur both in the fasting or postprandial state (reactive hypoglycemia). The pathophysiology of fasting hypoglycemia is thought to be related to malnutrition and increased energy expenditure in the setting of inflammation and acute infections. Reactive hypoglycemia is thought to be due to impaired first phase insulin release in response to a glucose load, followed by a delayed and extended second phase insulin secretion; ineffective counterregulatory response to dropping glucose levels may also play a role. The overall prevalence of spontaneous hypoglycemia varies from 7 to 69% as examined with oral glucose tolerance test (OGTT) or with continuous glucose monitoring (CGM) under free living conditions. Spontaneous hypoglycemia in CF is associated with worse lung function, higher hospitalization rates, and worse clinical status. In addition, patients with CF related diabetes on glucose-lowering therapies are at risk for iatrogenic hypoglycemia. In this article, we will review the pathophysiology, prevalence, risk factors, clinical implications, and management of spontaneous and iatrogenic hypoglycemia in patients with CF.

Increase in the Diagnosis and Severity of Presentation of Pediatric Type 1 and Type 2 Diabetes during the COVID-19 Pandemic.

INTRODUCTION: The impact of the COVID-19 pandemic on the incidence of pediatric type 1 (T1D) and type 2 diabetes (T2D) and severity of presentation at diagnosis is unclear. METHODS: A retrospective comparison of 737 youth diagnosed with T1D and T2D during the initial 12 months of the COVID-19 pandemic and in the preceding 2 years was conducted at a pediatric tertiary care center. RESULTS: Incident cases of T1D rose from 152 to 158 in the 2 years before the pandemic (3.9% increase) to 182 cases during the pandemic (15.2% increase). The prevalence of diabetic ketoacidosis (DKA) at T1D diagnosis increased over 3 years (41.4%, 51.9%, and 57.7%, p = 0.003); severe DKA increased during the pandemic as compared to the 2 years before (16.8% vs. 28%, p = 0.004). Although there was no difference in the mean hemoglobin A1c (HbA1c) between racial and ethnic groups at T1D diagnosis in the 2-years pre-pandemic (p = 0.31), during the pandemic HbA1c at T1D diagnosis was higher in non-Hispanic Black (NHB) youth (11.3 ± 1.4%, non-Hispanic White 10.5 ± 1.6%, Latinx 10.8 ± 1.5%, p = 0.01). Incident cases of T2D decreased from 54 to 50 cases (7.4% decrease) over the 2-years pre-pandemic and increased 182% during the pandemic (n = 141, 1.45 cases/month, p < 0.001). As compared to the 2-years pre-pandemic, cases increased most among NHB youth (56.7% vs. 76.6%, p = 0.001) and males (40.4% vs. 58.9%, p = 0.005). Cases of DKA (5.8% vs. 23.4%, p < 0.001) and hyperosmolar DKA (0 vs. 9.2%, p = 0.001) increased among youth with T2D during the pandemic. CONCLUSIONS: During the pandemic, the incidence and severity of presentation of T1D increased modestly, while incident cases of T2D increased 182%, with a nearly 6-fold increase in DKA and nearly a 10% incidence of hyperosmolar DKA. NHB youth were disproportionately impacted, raising concern about worsening of pre-existing health disparities during and after the pandemic.

Patterns of Continuous Glucose Monitor Use in Young Children Throughout the First 18 Months Following Type 1 Diabetes Diagnosis.

Objective: To describe sociodemographic and parent psychosocial characteristics associated with patterns of continuous glucose monitor (CGM) use across the first 18 months post-type 1 diabetes (T1D) diagnosis among young children. Methods: One hundred fifty-seven parent-child dyads enrolled in a behavioral intervention for parents of young children (1-6 years) newly diagnosed with T1D. Parents reported on baseline sociodemographic characteristics and psychosocial functioning; child CGM use was assessed at five time points during the first 18 months post-diagnosis. Results: Most participants (81.8%) used CGM at least once. Four CGM trajectories emerged (always, later/stable, inconsistent, and never). Participants with private insurance were more likely to be in the always, later/stable, or inconsistent groups versus the never group. Youth in the always and later/stable groups had lower mean HbA1c at 18 months than those in the never group. Conclusions: Given the health benefits of CGM, further exploration of barriers to CGM use in families with public health insurance is needed. ClinicalTrials.gov identifier: NCT02527525.

Juvenile Granulosa Cell Tumor as the Presenting Feature of McCune-Albright Syndrome.

INTRODUCTION: GNAS mutations have been reported in both McCune-Albright syndrome (MAS) and juvenile granulosa cell tumors (JGCT) but have never been reported simultaneously in the same patient. CASE PRESENTATION: A 15-year-old girl developed secondary oligomenorrhea. Laboratory studies revealed suppressed gonadotropin levels with markedly elevated estradiol and inhibin B levels. Pelvic ultrasound showed a 12-cm heterogeneous right adnexal mass; pelvic magnetic resonance imaging to further characterize the mass displayed heterogeneous bilateral femoral bone lesions initially concerning for metastatic disease. Positron emission tomography/computed tomography showed minimal 18F-fluorodeoxyglucose (FDG) uptake in the pelvic mass but unexpectedly revealed FDG uptake throughout the skeleton, concerning for polyostotic fibrous dysplasia in the context of MAS. The adnexal mass was excised and pathology confirmed a JGCT. The patient's affected bone and JGCT tissue revealed the same pathogenic GNAS p.R201C mutation, while her peripheral blood contained wild-type arginine at codon 201. CONCLUSION: This mutation has been previously reported in cases of MAS and JGCT but never simultaneously in the same patient. This demonstration of a GNAS mutation underlying both JGCT and MAS in the same patient raises questions about appropriate surveillance for patients with these conditions.