Mealtime Insulin BOLUS Score More Strongly Predicts HbA1c Than the Self-Care Inventory in Youth With Type 1 Diabetes.

BACKGROUND: To meet their glycated hemoglobin (HbA1c) goals, youth with type 1 diabetes (T1D) need to engage with their daily T1D treatment. The mealtime insulin Bolus score (BOLUS) is an objective measure of youth's T1D engagement which we have previously shown to be superior to other objective engagement measures in predicting youth's HbA1c. Here, to further assess the BOLUS score's validity, we compared the strengths of the associations between youth's HbA1c with their mean insulin BOLUS score and a valid, self-report measure of T1D engagement, the Self-Care Inventory (SCI). METHODS: One-hundred and five youth with T1D self-reported their T1D engagement using the SCI. We also collected two weeks of insulin pump data and a concurrent HbA1c level. We scored youth's SCI and calculated their mean insulin BOLUS score using standardized methods. For the analyses, we performed simple correlations, partial correlations, and multiple regression models. RESULTS: Youth had a mean age of 15.03 ± 1.97 years, mean time since diagnosis of 8.11 ± 3.26 years, and a mean HbA1c of 8.78 ± 1.49%. The sample included n = 58 boys (55%) and n = 96 families (91%) self-identified as white. Simple correlations between youth's age, HbA1c, SCI total score, and BOLUS score were all significant. Partial correlation and regression models revealed that youth's insulin BOLUS score was more strongly associated with HbA1c than the SCI. CONCLUSIONS: Youths' BOLUS score has better concurrent validity with HbA1c than the SCI. We should consider reporting the BOLUS score as an outcome metric in insulin pump data reports.

International Guideline Adherence in Girls with Turner Syndrome: Multiple Subspecialty Clinics Versus Coordinated Multidisciplinary Clinic.

OBJECTIVE: To evaluate the 2016 Cincinnati International Turner syndrome (TS) consensus guideline adherence within our pediatric tertiary referral center and determine if patients managed in our single-day, coordinated multidisciplinary clinic (MDC) format showed superior adherence rates when compared with those managed outside our MDC format. METHODS: We retrospectively reviewed the charts of patients with TS followed at our center from January 1, 2018, to April 30, 2020. The individual and overall adherence rates of 9 age-appropriate screening recommendations were evaluated along with rates of TS comorbidities within our cohort. RESULTS: A total of 111 girls met the study criteria. Sixty-eight were managed in the MDC and 43 were managed outside the MDC. Only 42% of all the girls met all 9 evaluated age-appropriate screening recommendations, of 47 girls, 33 (70%) were managed in MDC compared with 14 (30%) who were managed in the non-MDC. Girls managed in the MDC had higher screening adherence rates versus non-MDC girls for 7 of the 9 evaluated screenings with especially large differences noted for thyroid stimulating hormone (95% vs 78%, P = .034), auditory evaluation (97% vs 65%, P < .001), and HgA1c levels (82% vs 54%, P = .014). CONCLUSION: Girls managed in the MDC format showed higher rates of screening guideline adherence, both overall and with multiple specific screening tests, than those managed outside the MDC format. Overall guideline adherence remained low (42%), highlighting the need for continued optimization and improvement in guideline adherence in this unique subset of the population.

Accuracy of Three Commercial Home-Use Hemoglobin A1c Tests.

Background: The COVID-19 pandemic and the rapid expansion of telemedicine have increased the need for accurate and reliable capillary hemoglobin A1c (HbA1c) testing. Nevertheless, validation studies of commercially available products suitable for home use have been in short supply. Methods: Three commercial home-use capillary blood sample HbA1c tests (Home Access, CoreMedica, and A1cNow+) were evaluated in 219 participants with type 1 or type 2 diabetes (4-80 years years of age, HbA1c 5.1%-13.4% [32-123 mmol/mol]) at four clinical sites. Comparisons were made between HbA1c measurements from the commercial tests and paired venous samples for which HbA1c was measured at two central reference laboratories. The primary outcome was percentage of commercial HbA1c values within 5% of the corresponding reference values. Results: HbA1c values were within 5% (relative difference) of paired reference values for 82% of Home Access samples, 29% of CoreMedica samples, and 46% of A1cNow+ samples. Absolute differences were within 0.3% of the reference value for 75% of Home Access samples, 28% of CoreMedica samples, and 44% of A1cNow+ samples and exceeded 0.5% for 8%, 55%, and 37%, respectively. Conclusions: None of the commercial home-use HbA1c tests produced the National Glycohemoglobin Standardization Program goal of ≥90% measurements within 5% of a DCCT venous reference. However, the Home Access product performed substantially better than the CoreMedica or A1cNow+ products. Telemedicine is likely to persist as a mainstay of diabetes care well after the COVID-19 era. As such, accurate home-based HbA1c assessment represents an urgent need for the diabetes community.

Increased Prevalence of Beta-Cell Dysfunction despite Normal HbA1c in Youth and Young Adults with Turner Syndrome.

INTRODUCTION: Adult women with Turner syndrome (TS) have a high prevalence of diabetes and ß-cell dysfunction that increases morbidity and mortality, but it is unknown if there is ß-cell dysfunction present in youth with TS. This study aimed to determine the prevalence of ß-cell dysfunction in youth with TS and the impact of traditional therapies on insulin sensitivity (SI) and insulin secretion. METHODS: Cross-sectional, observational study recruited 60 girls with TS and 60 healthy controls (HC) matched on pubertal status. Each subject had a history, physical exam, and oral glucose tolerance test (OGTT). Oral glucose and c-peptide minimal modeling was used to determine ß-cell function. RESULTS: Twenty-one TS girls (35%) met criteria for prediabetes. Impaired fasting glucose was present in 18% of girls with TS and 3% HC (p value = 0.02). Impaired glucose tolerance was present in 23% of TS girls and 0% HC (p value <0.001). The hemoglobin A1c was not different between TS and HC (median 5%, p = 0.42). Youth with TS had significant reductions in SI, ß-cell responsivity (Φ), and disposition index (DI) compared to HC. These differences remained significant when controlling for body mass index z-score (p values: 0.0006, 0.002, <0.0001 for SI, Φ total, DI, respectively). CONCLUSIONS: ß-Cell dysfunction is present in youth with TS compared to controls. The presence of both reduced insulin secretion and SI suggest a unique TS-related glycemic phenotype. Based on the data from this study, we strongly suggest that providers employ serial OGTT to screen for glucose abnormalities in TS youth.

An Evaluation of Two Capillary Sample Collection Kits for Laboratory Measurement of HbA1c.

Background: The COVID-19 pandemic has impacted the conduct of clinic visits. We conducted a study to evaluate two academic laboratories' fingerstick capillary blood collection kits suitable for home use for laboratory measurement of HbA1c. Methods: Four clinical sites recruited 240 participants (aged 4-80 years, HbA1c 5.1%-13.5%). Capillary blood samples were obtained by the participant or parent using collection kits from two laboratories (University of Minnesota Advanced Research and Diagnostic Laboratory (ARDL) and Children's Mercy Hospital Laboratory (CMH)) and mailed under varying shipping conditions by United States Postal Service to the laboratories. Comparisons were made between HbA1c measurements from capillary samples and contemporaneously obtained venous samples. The primary outcome was percentage of capillary HbA1c values within 5% of the corresponding venous values. Results: HbA1c values were within 5% of venous values for 96% of ARDL kit specimens shipped with a cold pack and 98% without a cold pack and 99% and 99%, respectively, for the CMH kits. R2 values were 0.98, 0.99, 0.99, and 0.99, respectively. Results appeared similar across HbA1c levels and for pediatric and adult participants. Usability survey scores were high. Conclusions: Capillary blood collection kits, suitable for home use, from two academic laboratories, were demonstrated to be easy to use and provided results that are comparable with those obtained from venous specimens. Based on these results, there is strong evidence that HbA1c measurements from capillary specimens obtained with these specific kits can be used interchangeably with HbA1c measurements from venous specimens for clinical research and clinical care.

National Cooperative Growth Study: 25 Years of Growth Hormone Data, Insights, and Lessons for Future Registries.

BACKGROUND: The National Cooperative Growth Study (NCGS) data are reviewed from 1985-2010 to report on final demographic, efficacy, and safety findings, and to illustrate the value of long-term, real-world follow-up to physicians and patients. METHODS: The NCGS was a multicenter, open-label, observational, postmarketing surveillance study of Genentech growth hormone (GH) products for the treatment of children with growth failure in North America. FINDINGS: Data from 65,205 patients representing 240,951 patient-years of experience were collected. All etiological groups had clinically meaningful improvements in near-adult height SDS. Females and African Americans were under-represented in the NCGS with little change in accrual over time. The favorable safety profile of GH was validated through the registry. CONCLUSIONS: Twenty-five years of monitoring GH use through the NCGS yielded extensive insight into the utility of GH in various underlying etiologies. Demographic disparities were clear and became evident by analyzing data collected through the registry.

Employing a results-based algorithm to reduce laboratory utilization in ACTH stimulation testing.

BACKGROUND: The High Dose Adrenocorticotropic Hormone (ACTH) Stimulation Test is the gold standard to diagnose adrenal insufficiency. Normal adrenal function is defined as a peak cortisol response to pharmacologic stimulation with cosyntropin of ≥18 µg/dL. Our practice was to obtain cortisol levels at 0, 30 and 60 min after cosyntropin administration. Once a value of ≥18 µg/dL has been obtained, adrenal insufficiency is ruled out and there is little diagnostic utility in subsequent stimulated levels. METHODS: We aimed to decrease laboratory utilization by developing a results-based algorithm in the electronic medical record (EMR). Cortisol levels were analyzed on the 0 and 60 min samples; then an EMR discern rule automatically generated an order to analyze the 30-min sample if the 60-min cortisol level was subnormal. RESULTS: Exclusion of adrenal insufficiency was excluded using one stimulated cortisol level in 8% prior to algorithm development. After several plan-do-study-act cycles, 99% of normal tests were performed using only one stimulated cortisol level. CONCLUSIONS: This laboratory-based algorithm resulted in reduced laboratory utilization, and aligned our practice to recommendations of the Pediatric Endocrine Society. Similar algorithms could be created for other dynamic tests to reduce unnecessary laboratory utilization.

Proceedings from the Turner Resource Network symposium: the crossroads of health care research and health care delivery.

Turner syndrome, a congenital condition that affects ∼1/2,500 births, results from absence or structural alteration of the second sex chromosome. There has been substantial effort by numerous clinical and genetic research groups to delineate the clinical, pathophysiological, cytogenetic, and molecular features of this multisystem condition. Questions about the molecular-genetic and biological basis of many of the clinical features remain unanswered, and health care providers and families seek improved care for affected individuals. The inaugural "Turner Resource Network (TRN) Symposium" brought together individuals with Turner syndrome and their families, advocacy group leaders, clinicians, basic scientists, physician-scientists, trainees and other stakeholders with interest in the well-being of individuals and families living with the condition. The goal of this symposium was to establish a structure for a TRN that will be a patient-powered organization involving those living with Turner syndrome, their families, clinicians, and scientists. The TRN will identify basic and clinical questions that might be answered with registries, clinical trials, or through bench research to promote and advocate for best practices and improved care for individuals with Turner syndrome. The symposium concluded with the consensus that two rationales justify the creation of a TRN: inadequate attention has been paid to the health and psychosocial issues facing girls and women who live with Turner syndrome; investigations into the susceptibility to common disorders such as cardiovascular or autoimmune diseases caused by sex chromosome deficiencies will increase understanding of disease susceptibilities in the general population.

Use of aromatase inhibitors in children with short stature.

Estrogen has been shown to have an important role in skeletal maturation in both males and females. The use of aromatase inhibitors may provide a means to delay skeletal maturation and increase final height in children with short stature. These medications have been used primarily in women with breast carcinoma and also in children with autonomous estrogen production, such as patients with McCune-Albright Syndrome. Several studies have evaluated the safety and metabolic effects in adults. A few studies in children have evaluated the efficacy and safety of these medications. These studies demonstrate a beneficial effect on bone age advancement and predicted adult height. Other studies have evaluated the effects on bone mineral density, lipid metabolism and adrenal function in children. This review summarizes the studies in the pediatric population and some of the metabolic effects in adults.