Changes in Pediatric Type 2 Diabetes During the COVID-19 Pandemic.

Type 2 diabetes (T2D) is a growing concern among the pediatric population. During the coronavirus disease 2019 (COVID-19) pandemic, the incidence of pediatric T2D increased. This was more notable among males and Black people. Increased rates of T2D may be due to rising obesity rates observed during the pandemic, behavioral and nutritional changes due to the lockdown, and decreased structure typically provided by in-person schooling. New-onset T2D presentations are more severe than in years prior to the pandemic, with higher initial hemoglobin A1C levels and increased rates of diabetic ketoacidosis. Increased severity in presentation may be due to hesitation in seeking care, increased virtual care, and limited access to health care resources. The pathophysiology of the relationship between T2D and COVID-19 in youth is not clear at this time. More studies are needed to understand the true long-term impact of the COVID-19 pandemic on T2D in youth. [Pediatr Ann. 2024;53(7):e249-e253.].

Screening for diabetes distress and depression in routine clinical care for youth with type 1 diabetes.

OBJECTIVE: The purpose of this study is to examine diabetes distress as a potential mediator of the relationship between depression symptoms and diabetes outcomes, including hemoglobin A1c (hemoglobin A1c [HbA1c]) and diabetes management behaviors in a clinical sample of adolescents and young adults. METHODS: In a pediatric diabetes clinic, 716 youth (ages 12-21 years) completed measures of diabetes distress (Problem Areas in Diabetes-Teen [PAID-T]), a single-item of diabetes distress, and depression (Patient Health Questionnaire [PHQ-9]) as part of standard care. Electronic health records were extracted for the "Six Habits" and glycemic management (HbA1c). RESULTS: Overall, 3.6% (n = 26) of adolescents had clinically elevated diabetes distress and depression symptoms, 5.0% had diabetes distress alone, 8.7% had depression symptoms alone, and 82.7% had neither clinical elevation of diabetes distress nor depression symptoms. Results of mediation analysis demonstrated diabetes distress (both full and single-item measures) fully mediated the relationship between depression symptoms and HbA1c (p < .001). Also, mediation analysis results showcase incomplete mediation of the effect of the Six Habits score on HbA1c appears by PAID-T Diabetes Distress. CONCLUSIONS: In a clinical sample of youth with type 1 diabetes, both depressive symptoms and diabetes distress are associated with HbA1c. Furthermore, diabetes distress fully mediates the relationship between depressive symptoms and HbA1c. As part of standard clinical care, the single-item screener for diabetes distress captured similar results as the full-scaled PAID-T. With limited clinical resources, providers may consider focusing assessment and interventions on the psychological factor of diabetes distress within the diabetes clinic to maximize the impact on glycemic control and consider the use of single-item screening to identify distress.

A Novel Receivership Model for Transition of Young Adults With Diabetes: Experience From a Single-center Academic Transition Program.

OBJECTIVE: The transition from pediatric to adult care for young adults with diabetes represents an important but often challenging time characterized by a shift from a family-centered care model of pediatrics to a patient-centered care model of adult medicine. We developed a structured transition program based on an adult receivership model at a large academic medical center to improve care coordination and patient satisfaction with the transition process. METHODS: From 2016 to 2020, we implemented a series of quality improvement efforts for young adults aged 18 to 23 years with diabetes by incorporating best practices from the American Diabetes Association guidelines on care for emerging adults. We measured transition orientation attendance, patient satisfaction, hemoglobin A1c (HbA1c) pre- and post-transfer, and care gaps to determine the impact of the program. RESULTS: In this study, 307 individuals with type 1 diabetes and 16 individuals with type 2 diabetes were taken care of by the adult endocrinology department at the University of Michigan between January 1, 2016 and October 31, 2020. We observed high attendance rates (86% among internal transfers) and favorable patient satisfaction scores for the transition orientation session. Despite the glycemic challenges posed during the transition, HbA1c modestly yet significantly improved 1-year after transfer (-0.4%, P < .01). CONCLUSION: We successfully established and maintained a young adult diabetes transition program using a quality improvement approach. Future work will focus on reducing care gaps at the time of transfer, assessing long-term retention rates, and enhancing care coordination for patients referred from outside the health network.

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.

Using Human Induced Pluripotent Stem Cell-Derived Organoids to Identify New Pathologies in Patients With PDX1 Mutations.

BACKGROUND & AIMS: Two patients with homozygous mutations in PDX1 presented with pancreatic agenesis, chronic diarrhea, and poor weight gain, the causes of which were not identified through routine clinical testing. We aimed to perform a deep analysis of the stomach and intestine using organoids derived from induced pluripotent stem cells from PDX1188delC/188delC patients. METHODS: Gastric fundic, antral, and duodenal organoids were generated using induced pluripotent stem cell lines from a PDX1188delC/188delC patient and an isogenic induced pluripotent stem cell line where the PDX1 point mutation was corrected. RESULTS: Patient-derived PDX1188delC/188delC antral organoids exhibited an intestinal phenotype, whereas intestinal organoids underwent gastric metaplasia with significant reduction in enteroendocrine cells. This prompted a re-examination of gastric and intestinal biopsy specimens from both PDX1188delC/188delC patients, which recapitulated the organoid phenotypes. Moreover, antral biopsy specimens also showed increased parietal cells and lacked G cells, suggesting loss of antral identity. All organoid pathologies were reversed upon CRISPR-mediated correction of the mutation. CONCLUSIONS: These patients will now be monitored for the progression of metaplasia and gastrointestinal complications that might be related to the reduced gastric and intestinal endocrine cells. This study demonstrates the utility of organoids in diagnosing uncovered pathologies.

Feasibility of Electronic Health Record Assessment of 6 Pediatric Type 1 Diabetes Self-management Habits and Their Association With Glycemic Outcomes.

Importance: A low-burden electronic health record (EHR) workflow has been devised to systematize the collection and validation of 6 key diabetes self-management habits: (1) checks glucose at least 4 times/day or uses continuous glucose monitor (CGM); (2) gives at least 3 rapid-acting insulin boluses per day; (3) uses insulin pump; (4) delivers boluses before meals; (5) reviewed glucose data since last clinic visit, and (6) has changed insulin doses since the last clinic visit. Objective: To describe the performance of these habits and examine their association with hemoglobin A1c (HbA1c) levels and time in range (TIR). Design, Setting, and Participants: This cross-sectional study included individuals with known type 1 diabetes who were seen in a US pediatric diabetes clinic in 2019. Main Outcomes and Measures: Habit performance, total habit score (sum of 6 habits per person), HbA1c levels, and TIR. Results: Of 1344 patients, 1212 (609 [50.2%] males; 66 [5.4%] non-Hispanic Black; 1030 [85.0%] non-Hispanic White; mean [SD] age, 15.5 [4.5] years) were included, of whom 654 (54.0%) were using CGM and had a TIR. Only 105 patients (8.7%) performed all 6 habits. Habit performance was lower among older vs younger patients (age ≥18 years vs ≤12 years: 17 of 411 [4.1%] vs 57 of 330 [17.3%]; P < .001), Black vs White patients (3 [4.5%] vs 95 [9.2%]; P < .001), those with public vs private insurance (14 of 271 [5.2%] vs 91 of 941 [9.7%]; P < .001), and those with lower vs higher parental education levels (

Inequities in Health Outcomes in Children and Adults With Type 1 Diabetes: Data From the T1D Exchange Quality Improvement Collaborative.

Health care inequities among racial and ethnic groups remain prevalent. For people with type 1 diabetes who require increased medical access and care, disparities are seen in access to care and health outcomes. This article reports on a study by the T1D Exchange Quality Improvement Collaborative evaluating differences in A1C, diabetic ketoacidosis (DKA), severe hypoglycemia, and technology use among racial and ethnic groups. In a diverse cohort of nearly 20,000 children and adults with type 1 diabetes, A1C was found to differ significantly among racial and ethnic groups. Non-Hispanic Blacks had higher rates of DKA and severe hypoglycemia and the lowest rate of technology use. These results underscore the crucial need to study and overcome the barriers that lead to inequities in the care and outcomes of people with type 1 diabetes.

4-Hour postoperative PTH level predicts hypocalcemia after thyroidectomy in children.

BACKGROUND: Hypocalcemia occurs frequently after a total thyroidectomy in pediatric patients. Four hour postoperative PTH monitoring predicts the need for calcium supplementation in the adult thyroidectomy population. We evaluated the role of the 4 h postoperative PTH level in determining the need for calcium supplementation after thyroidectomy in the pediatric population. METHODS: This is a retrospective review of children undergoing total thyroidectomy by a single pediatric surgeon from July 2011 through July 2018. Intact PTH obtained four hours postoperatively determined the need for calcium supplementation for patients beginning in November 2014 onward. Serum total calcium levels were monitored concurrently with serum intact PTH levels. Serum calcium levels were followed in our Multispecialty Pediatric Endocrine Surgery clinic within the month following thyroidectomy. RESULTS: From July 2011 through July 2018, there were a total of 56 total thyroidectomies at our institution. Prior to November 2014, all pediatric total thyroidectomies received calcium supplementation per our institutional protocol. Based on ionized calcium levels, 26.3% (5/19) of children developed hypocalcemia. From November 2014 to July 2018, 37 pediatric patients required total thyroidectomies. 29.7% (11/37) had low 4-h postoperative PTH levels. 72.7% (8/11) patients with low 4-h postoperative PTH levels had corresponding postoperative day 1 total calcium levels less than 8.5 or ionized calcium levels less than 1.12, and five children (45.5%) developed symptomatic hypocalcemia. 70% (26/37) of children had normal 4-h postop PTH levels, with only 5 (19%) ever developing hypocalcemia. No patients with a normal postop PTH level developed symptomatic hypocalcemia or required IV calcium repletion. A single 4-h postoperative PTH <10 pg/dl for identifying hypocalcemia has a sensitivity of 81% and specificity of 91%, with AUC 0.81. CONCLUSION: The 4-h postoperative serum PTH level can help determine the need for calcium supplementation in pediatric patients undergoing total thyroidectomy, thereby reducing unnecessary calcium supplementation and serial lab draws to monitor for postoperative hypocalcemia. LEVEL OF EVIDENCE: Level II.

Malignant risk of indeterminate pediatric thyroid nodules-An institutional experience.

BACKGROUND: Few studies focus on pediatric thyroid nodules categorized under indeterminate diagnostic categories. The current study was conducted to assess the risk of malignancy of indeterminate pediatric thyroid nodules. METHODS: A search of the institutional electronic pathology database from 01/2011 to 09/2018 was performed to identify pediatric (<21 years old) thyroid nodules that were interpreted as follicular lesion of undetermined significance (FLUS), suspicious for follicular neoplasm (SFN), or suspicious for malignancy (SFM) and subsequently managed with surgery, repeat fine-needle aspiration (FNA), or ≥ 6 months of clinical/imaging monitoring. Results of follow-up (F/U) surgical resections and repeat FNA/Afirma tests, and clinical and radiologic data were collected. RESULTS: We identified 46 cases from 42 patients (11-20 years old, 33 females and 9 males), including 30 FLUS, 10 SFN, and 6 SFM. Twenty-five FLUS, ten SFN, and six SFM cases underwent surgery. The histology revealed carcinomas in 36% of FLUS, 20% of SFN, and 100% of SFM categories; follicular adenomas in 32% of FLUS and 80% of SFN categories; and benign nodules in 32% of FLUS category. All five nonsurgically treated FLUS cases were considered benign based on the findings of repeat FNA/Afirma tests (n = 3, 3-22 months F/U) or clinical/radiologic exams (n = 2, 8-12 months F/U). CONCLUSIONS: Based on a limited study cohort, malignancy was identified in 36%, 20%, and 100% of surgically managed pediatric thyroid nodules categorized as FLUS, SFN, and SFM, respectively; suggesting a markedly higher malignant rate than the implied malignant risk for FLUS and SFM categories in adults.

Transition from pediatric to adult care in emerging adults with type 1 diabetes: a blueprint for effective receivership.

For adolescents and emerging adults, the transition from pediatrics to adult care is fraught with challenges both inside and outside the clinical arena, including assuming independent care for diabetes, working with new adult providers, and overcoming concomitant psychosocial issues, while maintaining work/school-life balance. Not surprisingly, glycemic control in emerging adults with type 1 diabetes is amongst the worst in all age groups. Thus, new and comprehensive strategies are needed by both pediatric and adult diabetes care teams to support young adults during the transition to adult care. In this review, we focus on challenges during the transition period and provide evidence-based recommendations for a receivership model to assist adult diabetes care teams in addressing these concerns. By coordinating efforts with pediatrics providers, identifying strengths and deficiencies in self-care, establishing rapport with young adult patients, directly addressing prevalent psychosocial concerns, and developing a team-based approach to keep patients engaged, adult care teams can prioritize support for the most vulnerable transition patients. Improved strategies to propel emerging adult patients through the transition period towards habits leading to optimal glycemic control could have a major long-term impact on preventing diabetes-related complications.

Altered corneal biomechanical properties in children with osteogenesis imperfecta.

PURPOSE: To evaluate biomechanical corneal properties in children with osteogenesis imperfecta (OI). METHODS: A prospective, observational, case-control study was conducted on children 6-19 years of age diagnosed with OI. Patients with OI and healthy control subjects underwent complete ophthalmic examinations. Additional tests included Ocular Response Analyzer (ORA) and ultrasonic pachymetry. Primary outcomes were central corneal thickness (CCT), corneal hysteresis (CH), and corneal resistance factor (CRF). Intraocular pressure (IOP) was measured directly by either iCare or Goldmann applanation and indirectly by the ORA (Goldmann-correlated and corneal-compensated IOP). Statistically significant differences between OI and control groups were determined using independent samples t test. RESULTS: A total of 10 of 18 OI cases (mean age, 13 ± 4.37 years; 8 males) and 30 controls (mean age, 12.76 ± 2.62 years; 16 males) were able to complete the corneal biomechanics and pachymetry testing. Children with OI had decreased CH (8.5 ± 1.0 mm Hg vs 11.6 ± 1.2 mm Hg [P < 0.001]), CRF (9.0 ± 1.9 mm Hg vs 11.5 ± 1.5 [P < 0.001]) and CCT (449.8 ± 30.8 µm vs 568 ± 47.6 µm [P < 0.001]) compared to controls. The corneal-compensated IOP was significantly higher in OI cases (18.8 ± 3.1 mm Hg) than in controls (15.0 ± 1.6 mm Hg, P < 0.004), but there was no significant difference in Goldmann-correlated IOP (16.3 ± 4.2 mm Hg vs 15.8 ± 2.2 mm Hg). CONCLUSIONS: Collagen defects in OI alter corneal structure and biomechanics. Children with OI have decreased CH, CRF, and CCT, resulting in IOPs that are likely higher than measured by tonometry. These corneal alterations are present at a young age in OI. Affected individuals should be routinely screened for glaucoma and corneal pathologies.

Unexpected ethical dilemmas in sex assignment in 46,XY DSD due to 5-alpha reductase type 2 deficiency.

Sex assignment at birth remains one of the most clinically challenging and controversial topics in 46,XY disorders of sexual development (DSD). This is particularly challenging in deficiency of 5-alpha reductase type 2 given that external genitalia are typically undervirilized at birth but typically virilize at puberty to a variable degree. Historically, most individuals with 5-alpha reductase deficiency were raised females. However, reports that over half of patients who underwent a virilizing puberty adopted an adult male gender identity have challenged this practice. Consensus guidelines on assignment of sex of rearing at birth are equivocal or favor male assignment in the most virilized cases. While a male sex of rearing assignment may avoid lifelong hormonal therapy and/or allow the potential for fertility, female sex assignment may be more consistent with external anatomy in the most severely undervirilized cases. Herein, we describe five patients with 46,XY DSD due 5-alpha-reductase type 2 deficiency, all with a severe phenotype. An inter-disciplinary DSD medical team at one of two academic centers evaluated each patient. This case series illustrates the complicated decision-making process of assignment of sex of rearing at birth in 5-alpha reductase type 2 deficiency and the challenges that arise when the interests of the child, parental wishes, recommendations of the medical team, and state law collide.

Metformin; a review of its history and future: from lilac to longevity.

Metformin is a widely prescribed medication that has been used to treat children with type 2 diabetes in the United States for the past 15 years. Metformin now has a variety of clinical applications in pediatrics, and its potential clinical uses continue to expand. In addition to reviewing the current understanding of its mechanisms of action including the newly discovered effects on the gastrointestinal tract, we will also discuss current clinical uses in pediatrics, including in type 1 diabetes. Finally, we examine the existing state of monitoring for metformin efficacy and side effects and discuss prospective future clinical uses.

A cross-sectional view of the current state of treatment of youth with type 2 diabetes in the USA: enrollment data from the Pediatric Diabetes Consortium Type 2 Diabetes Registry.

OBJECTIVE: To describe the clinical characteristics, treatment approaches, clinical outcomes, and co-morbidities of youth with type 2 diabetes (T2D) enrolled in the Pediatric Diabetes Consortium (PDC) T2D Registry. METHODS: PDC enrolled 598 youth <21 yr of age with T2D from February 2012 to July 2015 at eight centers. Data were collected from medical records and interviews with participants and/or parents and included glycated hemoglobin (HbA1c), diabetes treatments, prevalence of diabetes comorbidities (hypertension (HTN), dyslipidemia (DL), microalbuminuria (MA), and nonalcoholic fatty liver disease (NAFLD). RESULTS: Insulin use was observed in 45% of those with T2D duration <1 yr, 44% for 1-<2 yr, 55% for 2-3 yr and 60% for ≥4 yr. Median HbA1c was 6.7% (50 mmol/mol), 8.5% (69 mmol/mol), 9.6% (81 mmol/mol), and 9.7% (82 mmol/mol) in those with disease duration <1, 1-<2, 2-3 and ≥4 yr, respectively. Only 33 and 11% of those with HTN and DL respectively, were being treated. MA and NAFLD were observed in 5-6% of the participants. Prevalence of HTN was associated with higher BMI (p < 0.001), DL with higher HbA1c (p < 0.001), and MA with longer diabetes duration (p = 0.001). CONCLUSIONS: Frequency of insulin therapy in youth with T2D was associated with increased disease duration and those with longer duration rarely achieve target HbA1c level. This highlights the aggressive course of T2D in youth and adolescents. Additionally, co-morbidities are not being adequately treated. Follow up data from the PDC will provide additional important information about the natural history of T2D and patterns of gaps in treatment.

Advances in the Classification and Treatment of Osteogenesis Imperfecta.

Osteogenesis imperfecta (OI) is a rare disorder of type 1 collagen with 13 currently identified types attributable to inherited abnormalities in type 1 collagen amount, structure, or processing. The disease is characterized by an increased susceptibility to bony fracture. In addition to the skeletal phenotype, common additional extraskeletal manifestations include blue sclerae, dentinogenesis imperfecta, vascular fragility, and hearing loss. Medical management is focused on minimizing the morbidity of fractures, pain, and bone deformities by maximizing bone health. Along with optimizing Vitamin D status and calcium intake and physical/occupational therapy, individualized surgical treatment may be indicated. Pharmacological therapy with bisphosphonate medications is now routinely utilized for moderate to severe forms and appears to have a good safety profile and bone health benefits. New therapies with other anti-resorptives as well as anabolic agents and transforming growth factor (TGF)ß antibodies are in development. Other potential treatment modalities could include gene therapy or mesenchymal cell transplant. In the future, treatment choices will be further individualized in order to reduce disease morbidity and mortality.

Isodicentric Y mosaicism involving a 46, XX cell line: Implications for management.

Carriers of isodicentric Y (idicY) mosaicism exhibit a wide range of clinical features, including short stature, gonadal abnormalities, and external genital anomalies. However, the phenotypic spectrum for individuals carrying an idicY and a 46, XX cell line is less clearly defined. A more complete description of the phenotype related to idicY is thus essential to guide management related to pubertal development, fertility, and gonadoblastoma risk in mosaic carriers. Findings from the evaluation of twin females with an abnormal karyotype, 48, XX, +idic(Yq) x2/47, XX, +idic(Yq)/46, XX, are presented to highlight the importance of interdisciplinary care in the management of multifaceted disorders of sex development.

Ectopic Cushing syndrome secondary to metastatic medullary thyroid cancer in a child with multiple endocrine neoplasia syndrome type 2B: clues to early diagnosis of the paraneoplastic syndromes.

We describe a 13-year-old male with multiple endocrine neoplasia syndrome type 2B with medullary thyroid carcinoma who was diagnosed with ectopic adrenocorticotropin-dependent Cushing syndrome. This report highlights the importance of monitoring for paraneoplastic syndrome in MEN and clues to the diagnosis of this complication provided by growth patterns.

Pediatric parenting stress and its relation to depressive symptoms and fear of hypoglycemia in parents of young children with type 1 diabetes mellitus.

Parents of young children with type 1 diabetes (T1DM) maintain full responsibility for their child's daily diabetes self-care and thus may be vulnerable to experiencing parenting stress. This study examined several psychological correlates of pediatric parenting stress in parents of young children with T1DM. Parents of 39 young children with T1DM (ages 2-7 years) completed measures of pediatric parenting stress, mealtime behavior problems, depressive symptoms, and fear of hypoglycemia. For parents of young children, higher stress frequency and difficulty were associated with higher parental depressive symptoms and fear. Regression analyses identified that 58% of the variance in stress frequency was associated with parental depressive symptoms. For stress difficulty, 68% of the variance was associated with parental depressive symptoms and fear. Pediatric parenting stress is common in parents of young children with T1DM. Stress and the psychological correlates measured in this study are amenable to intervention and should be regularly assessed in parents of young children with T1DM.