Congenital hyperinsulinism (CHI) is genetically heterogeneous, caused by pathogenic variants in multiple known genes regulating insulin secretion from the pancreatic β‐cells. The ABCC8 gene encodes ...the sulfonylurea receptor 1 (SUR1), a key player in insulin secretion, and pathogenic variants in ABCC8 are the most common cause of CHI. With increased application of genetic testing in clinical practice, variants of unknown clinical significance (VUS) are commonly reported. Additional functional investigation for variant pathogenicity is fundamental in establishing definitive molecular diagnosis and in guiding clinical management. However, due to the lack of ubiquitous tissue expression of these genes, obtaining functional studies on affected tissue has been challenging. We present a case of severe congenital hyperinsulinism which required a near‐total pancreatectomy. CHI gene sequencing identified a homozygous silent variant in ABCC8 located on the last nucleotide of exon 38, c.4608G>A (p.Ala1536Ala). The total RNA was isolated from pancreas resected at the time of pancreatectomy. RNA sequencing and expression analysis demonstrated exon 38 skipping and decreased RNA expression, which supports the pathogenicity of this variant. This case highlights the feasibility of functional studies of VUS on resected pancreatic tissue. The result expands the mutation spectrum in ABCC8 and allows precise genetic counseling to affected families.
Introduction & Objective: Children with acute lymphoblastic leukemia/lymphoma (ALL/LLy) may experience significant treatment-related toxicities, graded per National Cancer Institute-prescribed ...definitions. During induction, development of hyperglycemia can cause significant morbidity, including monitoring, medical management, or prolonged hospitalization. An objective of the pilot study is to evaluate feasibility and efficacy of continuous glucose monitoring system (CGM) in pediatric ALL/LLy patients. Methods: A prospective study of patients with ALL/LLy aged 1-21 years began on 2/11/2022 and is ongoing at Children’s Healthcare of Atlanta. After consent to a parent study measuring markers of hyperglycemia risk, patients are invited to enroll in a blinded CGM arm. Libre pro was utilized. Demographic and clinical data (family history of diabetes, medications, targeted AEs presence and grade) are obtained via manual chart abstraction. Descriptive statistics were calculated for study variables. Results: As of December 2023, 53 patients completed induction in the parent study: 30 (57%) male, 35 (66%) White, 13 (35%) Black, and 42 (79%) Non-Hispanic/Latino. Diagnosis age median was 5.1 years (1.3-18.6). All patients experienced hyperglycemia: 41 (77%) grade 1; 12 (23%) grade 2+ (grade 2: n=7, 13%; grade 3: n=5, 9%). Grade 2+ hyperglycemia patients were more like to have a family history of diabetes (7/12, 53% vs. 8/41, 20%, p=0.03). Insulin management was required in grade 3 hyperglycemia. CGM was consented to and worn by 9 patients (17%) with an average CGM active time of 77% (88-92%) and 6 patients had >70% wear time. During induction, 4 (44%) of the CGM arm required, compared to 1 (2%) of the non-CGM arm. CGM utilizers had no skin rash or infection at CGM site. Conclusion: A pilot study of children with ALL/LLy showed blinded CGM technology worn during induction therapy has reliable results without complications. Additional studies are needed to explore expanded use of CGM in similar patient populations. Disclosure K. Cossen: None. T.P. Miller: None. N. DeGroote: None. L. Strange: None. J. Stevenson: None. S.M. Castellino: Advisory Panel; Seagen Inc, Bristol-Myers Squibb Company. Funding Emory/CHOA Pediatric Research Alliance (2021-00109546)
Objective: Recent guidelines for management of T1D with exercise prompted us to determine if exercise management differs in T1D patients <15 yo with high or low hypoglycemia (hypo) awareness.
...Methods: 229 subjects or caretakers in a single academic practice completed a modified T1D Exchange questionnaire, describing hypo awareness and exercise management (changes of carbohydrate (carb) intake and insulin doses). Hypo awareness was self-scored on a 5-point scale. Hypo awareness was defined as high (always/often) or low (never/rarely) (n=167). Patients had to exercise at least 1 day/week (mean 4.9) (n=158). Changes to carb intake for exercise were scored on a Never-to-Always 5-point scale. Insulin changes for exercise were scored on a yes/no scale. Because of differences in hypo awareness (p=0.0002), patients were divided into ages <8 year olds (yo) (n=35) and 8-14 yo (n=123). Fisher exact or Student t-test was applied.
Results: Between high and low hypo awareness groups, no significant differences were seen within each age category for: age at diagnosis, duration of T1D, insulin administration method, daily insulin dose, HbA1C, glucose meter checks/day, glucose checks <70mg/dL, and mean blood glucose. Children <8 yo were more likely to wear continuous glucose monitors (CGM) than 8-14 yo (34% vs. 24%; p=0.0002). Across all ages, hypo awareness was not associated with differences with insulin management (p=0.43) or carb use (p=0.18) before or during exercise. Increased CGM use was observed in low hypo awareness (48%) compared to high hypo awareness children (21%) (p=0.005), particularly among children <8 yo (57% vs. 19%; p=0.03) vs. 8-14 yo (40% vs. 21%; p=0.2).
Discussion: Increased CGM use was observed among patients <8 yo with low hypo awareness. Nonetheless, hypo awareness did not relate to adjustments of carb intake or insulin dose for exercise. This presents an educational opportunity to improve exercise-induced blood glucose fluctuation.
Disclosure
K. Cossen: None. B. Patterson: None. A. Muir: None.
Despite documented benefits of diabetes technology in managing type 1 diabetes, inequities persist in the use of these devices. Provider bias may be a driver of inequities, but the evidence is ...limited. Therefore, we aimed to examine the role of race/ethnicity and insurance-mediated provider implicit bias in recommending diabetes technology.
We recruited 109 adult and pediatric diabetes providers across 7 U.S. endocrinology centers to complete an implicit bias assessment composed of a clinical vignette and ranking exercise. Providers were randomized to receive clinical vignettes with differing insurance and patient names as proxy for Racial-Ethnic identity. Bias was identified if providers: (1) recommended more technology for patients with an English name (Racial-Ethnic bias) or private insurance (insurance bias), or (2) Race/Ethnicity or insurance was ranked high (Racial-Ethnic and insurance bias, respectively) in recommending diabetes technology. Provider characteristics were analyzed using descriptive statistics and multivariate logistic regression.
Insurance-mediated implicit bias was common in our cohort (
= 66, 61%). Providers who were identified to have insurance-mediated bias had greater years in practice (5.3 ± 5.3 years vs. 9.3 ± 9 years,
= 0.006). Racial-Ethnic-mediated implicit bias was also observed in our study (
= 37, 34%). Compared with those without Racial-Ethnic bias, providers with Racial-Ethnic bias were more likely to state that they could recognize their own implicit bias (89% vs. 61%,
= 0.001).
Provider implicit bias to recommend diabetes technology was observed based on insurance and Race/Ethnicity in our pediatric and adult diabetes provider cohort. These data raise the need to address provider implicit bias in diabetes care.
Objectives: The goal was to implement a risk profile that would prospectively identify youth with T1D at risk of severe hypoglycemia (SH) over the course of 1 year. We hypothesized that subjects with ...specific risk factors such as prior SH, a high frequency of nocturnal hypoglycemia (NH), and impaired hypoglycemia awareness would have a high rate of SH within the following year. If confirmed, an accurate assessment can lead to efficient application of interventions to reduce future risk of SH.
Methods: 404 subjects were followed for 14 months for SH, defined as a seizure, coma or loss of consciousness in the setting of presumed hypoglycemia (ISPAD guidelines). Subjects completed a survey that queried about SH, NH, and hypoglycemia unawareness. Comparisons were made using Chi-squared or Fisher’s exact tests for categorical variables and Wilcoxon Rank-Sum tests for continuous variables.
Results: Of the 404 enrolled, 18 subjects had SH in 14 months (4.46%). In the univariate analysis, those who had SH had indicated SH on the enrollment questionnaire (p-value 0.0015) and hypoglycemia unawareness as always or often (p-value 0.0259). Subjects with SH were more likely to wear CGMs (p-value 0.0369). Subject characteristics, T1D management, insurance, and NH were not statistically significant. In addition, we evaluated the 13 subjects who indicated on their initial questionnaire SH in the prior three months. In the univariate analysis, those subjects had more NH defined as ≥2 nights in a 3 month period (P=0.006) and less hypoglycemia awareness (P=0.030). With regards to insulin management, they had a lower insulin sensitivity factor (P=0.012) and higher proportion of basal insulin (P=0.003).
Conclusions: In a diverse cohort of T1D, this study shows the ability to identify pediatric subjects at risk for SH with hypoglycemia unawareness and prior SH. As SH is a rare event, as this study is expanded, there is the opportunity for a scored risk questionnaire to capture T1D youth at risk for SH.
Disclosure
K. Cossen: None. J. Figueroa: None. A.B. Muir: None.
Although guidelines for prescribing insulin pumps to patients with type 1 diabetes (T1D) focus on patient assessment, sociological research shows decision-making is influenced by the organizations ...within which actors are embedded. However, how organizational context shapes unequal resource allocation by race and class is less well understood. To investigate this, we compare two pediatric endocrinology centers differing in racial and socio-economic equity in pump use. Using over 400 h of observations and 16 provider interviews, we find allocation is shaped by how organizations use patient cultural health capital to determine pump eligibility, frame technology use, and structure decision-making processes. Overall, findings extend health inequalities research by describing how organizations shape technology resource allocation by race and class.
•Unequal tech allocation by race and class is influenced by organizational context.•Organizations' constitution of cultural health capital shapes technology allocation.•How organizations frame technology use shapes technology allocation.•How organizations structure decision-making also shapes technology allocation.•Organizational context matters for race- and class-based health inequality.
SARS-CoV-2 infection increases the risk of diabetes and diabetic ketoacidosis (DKA) in both adults and children. We investigated the clinical course of new-onset type 2 diabetes in youth presenting ...with DKA during the COVID-19 pandemic.
This single-center retrospective cohort study included 148 subjects with obesity aged 10 to 21 years, admitted with DKA from January 2018 to January 2022. Groups were defined by the presence of DKA precipitant: any infection (n = 38, 26%), which included the SARS-CoV-2 (n = 10, 7%) and other infection (n = 28, 19%) groups, and no infection (n = 110, 74%). The primary outcome was insulin discontinuation within a 12-month follow-up.
The mean age was 14.9 years (IQR, 13.8-16.5), and age-adjusted body mass index (%) was 99.1 (IQR, 98.0-99.5) with 85.8% identifying as Black or Hispanic. There were no differences in DKA severity among groups. The incidence of DKA was higher during the pandemic (March 2020-January 2022, n = 117) than in the prepandemic period (January 2018-February 2020, n = 31). Within the first year after the acute DKA episode, 46 patients discontinued all insulin within 9 months (IQR, 4-14). Sixteen subjects restarted insulin 10 months (IQR, 6.5-11.0) after insulin discontinuation. Infection with SARS-CoV-2 at diagnosis was not associated with the likelihood (P =.57) or timing (P =.27) of discontinuing all insulin within 1 year, nor was having any infection.
The incidence of DKA at the onset of type 2 diabetes was higher during the SARS-CoV-2 pandemic than in the prepandemic period. SARS-CoV-2 infection was not associated with DKA severity or insulin discontinuation within the first year of diagnosis in youth with new-onset type 2 diabetes and DKA.
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