Social Determinants of Health Screening in Type 1 Diabetes Management.

Type 1 diabetes management is intricately influenced by social determinants of health. Economic status impacts access to vital resources like insulin and diabetes technology. Racism, social injustice, and implicit biases affect equitable delivery of care. Education levels affect understanding of self-care, leading to disparities in glycemic outcomes. Geographic location can limit access to health care facilities. Stressors from discrimination or financial strain can disrupt disease management. Addressing these social factors is crucial for equitable diabetes care, emphasizing the need for comprehensive strategies that go beyond medical interventions to ensure optimal health outcomes for all individuals with type 1 diabetes.

Congenital Hypothyroidism: Screening and Management.

ABSTRACT: Untreated congenital hypothyroidism (CH) leads to intellectual disabilities. Prompt diagnosis by newborn screening (NBS) leading to early and adequate treatment results in grossly normal neurocognitive outcomes in adulthood. However, NBS for hypothyroidism is not yet established in all countries globally. Seventy percent of neonates worldwide do not undergo NBS.The initial treatment of CH is levothyroxine, 10 to 15 mcg/kg daily. The goals of treatment are to maintain consistent euthyroidism with normal thyroid-stimulating hormone and free thyroxine in the upper half of the age-specific reference range during the first 3 years of life. Controversy remains regarding detection of thyroid dysfunction and optimal management of special populations, including preterm or low-birth weight infants and infants with transient or mild CH, trisomy 21, or central hypothyroidism.Newborn screening alone is not sufficient to prevent adverse outcomes from CH in a pediatric population. In addition to NBS, the management of CH requires timely confirmation of the diagnosis, accurate interpretation of thyroid function testing, effective treatment, and consistent follow-up. Physicians need to consider hypothyroidism in the face of clinical symptoms, even if NBS thyroid test results are normal. When clinical symptoms and signs of hypothyroidism are present (such as large posterior fontanelle, large tongue, umbilical hernia, prolonged jaundice, constipation, lethargy, and/or hypothermia), measurement of serum thyroid-stimulating hormone and free thyroxine is indicated, regardless of NBS results.

Congenital Hypothyroidism: Screening and Management.

Untreated congenital hypothyroidism (CH) leads to intellectual disabilities. Newborn screening (NBS) for CH should be performed in all infants. Prompt diagnosis by NBS leading to early and adequate treatment results in grossly normal neurocognitive outcomes in adulthood. However, NBS for hypothyroidism is not yet practiced in all countries globally. Seventy percent of neonates worldwide do not undergo NBS. The recommended initial treatment of CH is levothyroxine, 10 to 15 mcg/kg daily. The goals of treatment are to maintain consistent euthyroidism with normal thyroid-stimulating hormone and with free thyroxine in the upper half of the age-specific reference range during the first 3 years of life. Controversy remains regarding the detection of thyroid dysfunction and optimal management of special populations, including preterm or low-birth-weight infants and infants with transient or mild CH, trisomy 21, or central hypothyroidism. NBS alone is not sufficient to prevent adverse outcomes from CH in a pediatric population. In addition to NBS, the management of CH requires timely confirmation of the diagnosis, accurate interpretation of thyroid function testing, effective treatment, and consistent follow-up. Physicians need to consider hypothyroidism in the face of clinical symptoms, even if NBS thyroid test results are normal. When clinical symptoms and signs of hypothyroidism are present (such as large posterior fontanelle, large tongue, umbilical hernia, prolonged jaundice, constipation, lethargy, and/or hypothermia), measurement of serum thyroid-stimulating hormone and free thyroxine is indicated, regardless of NBS results.

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.

Frequency and Severity of Hypothyroidism During TKI Therapy in the Pediatric and Young Adult Population.

Tyrosine kinase inhibitors that target vascular endothelial growth factor receptor [VEGFR-TKI] are a class of targeted therapies approved for treatment of several malignancies and are increasingly used in the pediatric population. Development of hypothyroidism during VEGFR-TKI therapy is well described in adults; however, there are no available data in children. Importantly, hypothyroidism during childhood can negatively impact growth and neurodevelopment. This retrospective study is the first to document frequency and severity of VEGFR-TKI induced hypothyroidism in pediatric and young adult patients. Patients included were ≤25 years of age and treated with at least one VEGFR-TKI between 2010 and 2018 at Cincinnati Children's Hospital Medical Center. After review of clinical and demographic data, 69 patients were identified. Of these, 19 (27.5%) developed thyroid dysfunction defined as Thyroid-stimulating hormone≥5 mIU/mL during therapy. Twelve of those patients had overt hypothyroidism with documentation of low free thyroxine and/or levothyroxine initiation. Mean exposure time to VEGFR-TKI before thyroid dysfunction was 2.8 (0.5-10.4) months. These results suggest moderate risk of developing thyroid dysfunction during VEGFR-TKI therapy in pediatric and young adult patients. Baseline thyroid hormone screening should be performed and repeated frequently during the first year of therapy in the pediatric population.

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.

Comparing adolescent self staging of pubertal development with hormone biomarkers.

OBJECTIVES: Physical examinations to characterize pubertal maturation may be unacceptable for children enrolled in research studies. Studies confirm the utility of pubertal self staging for research, but there has been limited comparison of self examination with hormone biomarkers. Our objective was to assess concordance of pubertal self staging with hormone biomarkers of puberty. METHODS: Participants were enrolled in the Health Outcomes and Measures of the Environment Study, a longitudinal pregnancy and birth cohort study. At age 12 years, 139 females and 112 males completed pubertal self staging including breast and pubic hair development in females and pubic hair development in males. No clinical physical examination was performed. Hormone concentrations were measured in 102 females and 96 males including serum dehydroepiandrosterone sulfate, luteinizing hormone, and follicle-stimulating hormone in all; estradiol in females; and testosterone in males. RESULTS: Estradiol was significantly associated with female breast stage, even when adjusted for BMI, with geometric least squares means (95%CI) of 13.2 (8.7, 20.2), 38.3 (29.9, 49.1), 59.4 (39.8, 88.6), and 81.2 (45.6, 144) pg/mL for breast stage 1-2, 3, 4, and 5, respectively. Testosterone was significantly associated with male pubic hair stage, with adjusted geometric least squares means (95%CI) of 37.6 (19.9, 71.1), 43.4 (27.7, 68.3), 126 (78.4, 203), 275 (146, 521), and 559 (237, 1319) ng/dL for pubic hair stage 1, 2, 3, 4, and 5, respectively. CONCLUSIONS: Self assessed pubertal development was positively associated with hormonal biomarkers of puberty.

Treatment-Induced Neuropathy of Diabetes in Youth: Case Series of a Heterogeneous and Challenging Complication.

Treatment-induced neuropathy of diabetes (TIND) is a small fiber neuropathy precipitated by rapid correction of hyperglycemia. Literature on TIND in pediatric diabetes is scarce. We present 7 cases of TIND in children and young adults, increasing awareness of this condition in pediatric diabetes and broadening the scope of published knowledge.

Untreated congenital hypothyroidism due to loss to follow-up: developing preventive strategies through quality improvement.

Background Children with congenital hypothyroidism (CH) are at risk for preventable intellectual disability without adequate medical management. The purpose of this manuscript is to discuss quality improvement (QI)-based processes for improving provider adherence to practice guidelines and ultimately identifying at-risk patients with chronic illness prior to the occurrence of adverse events. Methods Our study population included patients ages ≤3 years diagnosed with CH; lost to follow-up was defined as >180 days since last evaluation by an endocrinology provider. Iterative testing of interventions focused on establishing standardized care through (1) registry-based identification, (2) scheduling future appointments during current visits, (3) outreach to patients lost to follow-up and (4) provider and family education of current practice guidelines. Results A population-validated, electronic medical registry identified approximately 100 patients ages ≤3 years diagnosed with CH; initially, 12% of patients met criteria for lost to follow-up. Through serial testing of interventions, the rate of loss to follow-up declined to the goal of <5% within 8 months. Additional measures showed improvement in provider adherence to standard of care. All patients identified as lost to follow-up initially were seen within the first 3 months of intervention. Conclusions Applying QI methodology, a multidisciplinary team implemented a process to identify and contact high-risk CH patients with inadequate follow-up. Focused interventions targeting population management, scheduling and patient/provider education yield sustained improvement in the percentage of patients with a chronic condition who are lost to follow-up.

Partial growth hormone insensitivity and dysregulatory immune disease associated with de novo germline activating STAT3 mutations.

Germinal heterozygous activating STAT3 mutations represent a novel monogenic defect associated with multi-organ autoimmune disease and, in some cases, severe growth retardation. By using whole-exome sequencing, we identified two novel STAT3 mutations, p.E616del and p.C426R, in two unrelated pediatric patients with IGF-I deficiency and immune dysregulation. The functional analyses showed that both variants were gain-of-function (GOF), although they were not constitutively phosphorylated. They presented differences in their dephosphorylation kinetics and transcriptional activities under interleukin-6 stimulation. Both variants increased their transcriptional activities in response to growth hormone (GH) treatment. Nonetheless, STAT5b transcriptional activity was diminished in the presence of STAT3 GOF variants, suggesting a disruptive role of STAT3 GOF variants in the GH signaling pathway. This study highlights the broad clinical spectrum of patients presenting activating STAT3 mutations and explores the underlying molecular pathway responsible for this condition, suggesting that different mutations may drive increased activity by slightly different mechanisms.

Clinical and Psychosocial Factors Associated With Suicidal Ideation in Adolescents With Type 1 Diabetes.

PURPOSE: This study delineates clinical and psychosocial characteristics of adolescents with type 1 diabetes and suicidal ideation (SI) and reports clinical and psychosocial outcomes after mental health intervention (safety assessment and brief in-clinic intervention). METHODS: Adolescents aged 13-17 years with type 1 diabetes completed the Children's Depression Inventory (CDI) from January 2011 to 2012. Youth with significant depressive symptoms and/or SI endorsement underwent mental health intervention. Two control subjects were matched to each adolescent endorsing SI and compared using t-tests to assess clinical and psychosocial variables. Trajectory of depressive symptoms and outcomes for case subjects were observed through January 2013. RESULTS: Twenty-seven percent (127/473) exhibited moderate to high risk for depression based on CDI scores and 38 (8%) endorsed SI. Adolescents who endorsed SI were more likely to have higher CDI scores and public insurance when compared with youth who denied SI. There was no difference in glycemic control, measured by hemoglobin A1c, between case and control groups. During the year after intervention, 28 participants who initially endorsed SI underwent repeat assessment; mean CDI scores declined by 10.57 (standard deviation: 6.92) points and 78% no longer endorsed SI. CONCLUSIONS: Given the potential lethality of insulin when taken in intentional overdose, the need for consistent identification of suicidality is an important feature of depression screening. Study findings indicate statistically significant differences in depressive symptoms and insurance status, when comparing adolescents who endorsed SI to those who denied. Improvement in depressive symptoms and SI endorsement occurred after integrating brief mental health intervention into diabetes visits.