Diabetes Study of Children of Diverse Ethnicity and Race: Study design.

AIMS: Determining diabetes type in children has become increasingly difficult due to an overlap in typical characteristics between type 1 diabetes (T1D) and type 2 diabetes (T2D). The Diabetes Study in Children of Diverse Ethnicity and Race (DISCOVER) programme is a National Institutes of Health (NIH)-supported multicenter, prospective, observational study that enrols children and adolescents with non-secondary diabetes. The primary aim of the study was to develop improved models to differentiate between T1D and T2D in diverse youth. MATERIALS AND METHODS: The proposed models will evaluate the utility of three existing T1D genetic risk scores in combination with data on islet autoantibodies and other parameters typically available at the time of diabetes onset. Low non-fasting serum C-peptide (<0.6 nmol/L) between 3 and 10 years after diabetes diagnosis will be considered a biomarker for T1D as it reflects the loss of insulin secretion ability. Participating centres are enrolling youth (<19 years old) either with established diabetes (duration 3-10 years) for a cross-sectional evaluation or with recent onset diabetes (duration 3 weeks-15 months) for the longitudinal observation with annual visits for 3 years. Cross-sectional data will be used to develop models. Longitudinal data will be used to externally validate the best-fitting model. RESULTS: The results are expected to improve the ability to classify diabetes type in a large and growing subset of children who have an unclear form of diabetes at diagnosis. CONCLUSIONS: Accurate and timely classification of diabetes type will help establish the correct clinical management early in the course of the disease.

Plasma amino acid signatures define types of pediatric diabetes.

BACKGROUND & AIMS: Metabolic biomarkers with pathophysiological relevance is lacking in pediatric diabetes. We aimed to identify novel metabolic biomarkers in pediatric type 1 (T1D) and type 2 diabetes (T2D). We hypothesized that (1) targeted plasma metabolomics, focused on plasma amino acid concentrations, could identify distinctively altered patterns in children with T1D or T2D, and (2) there are specific changes in concentrations of metabolites related to branch chain amino acids (BCAA) and arginine metabolism in children with T2D. METHODS: In a pilot study, we enrolled children with T1D (n = 15) and T2D (n = 13), and healthy controls (n = 15). Fasting plasma amino acid concentrations were measured by ultra-performance liquid chromatography, and compared between the groups after adjustment for confounding factors. RESULTS: The mean age (SD) of participants was 16.4 (0.9) years. There were no group differences in age, gender, race/ethnicity, or 24-h protein intake. Mean BMI percentile was higher in the T2D than the T1D group or controls (p < 0.001). The T2D group had lower arginine, citrulline, glutamine, glycine, phenylalanine, methionine, threonine, asparagine and symmetric dimethylarginine (SDMA) but higher aspartate than controls, after adjusting for BMI percentiles (all p < 0.05). Children with T2D also had lower glycine but higher ornithine, proline, leucine, isoleucine, valine, total BCAA, lysine and tyrosine than those with T1D after adjusting for confounding factors (all p < 0.05). Children with T1D had lower phenylalanine, methionine, threonine, glutamine, tyrosine, asymmetric dimethylarginine (ADMA) and SDMA than controls (all p < 0.05). CONCLUSIONS: Children with T2D and T1D have distinct fasting plasma amino acid signatures that suggest varying pathogenic mechanisms and could serve as biomarkers for these conditions.

An Automated Risk Index for Diabetic Ketoacidosis in Pediatric Patients With Type 1 Diabetes: The RI-DKA.

Identifying patients at high risk for diabetic ketoacidosis (DKA) is crucial for informing efforts at preventive intervention. This study sought to develop and validate an electronic medical record (EMR)-based tool for predicting DKA risk in pediatric patients with type 1 diabetes. Based on analysis of data from 1,864 patients with type 1 diabetes, three factors emerged as significant predictors of DKA: most recent A1C, type of health insurance (public vs. private), and prior DKA. A prediction model was developed based on these factors and tested to identify and categorize patients at low, moderate, and high risk for experiencing DKA within the next year. This work demonstrates that risk for DKA can be predicted using a simple model that can be automatically derived from variables in the EMR.

A Comprehensive System for Identifying Patients With Type 1 Diabetes at Increased Risk for Diabetic Ketoacidosis at Texas Children's Hospital.

Quality Improvement Success Stories are published by the American Diabetes Association in collaboration with the American College of Physicians and the National Diabetes Education Program. This series is intended to highlight best practices and strategies from programs and clinics that have successfully improved the quality of care for people with diabetes or related conditions. Each article in the series is reviewed and follows a standard format developed by the editors of Clinical Diabetes. The following article describes a project at Texas Children's Hospital aimed at improving identification of patients with type 1 diabetes at high risk for diabetic ketoacidosis.

Suicide Risk in Youth and Young Adults with Type 1 Diabetes: a Review of the Literature and Clinical Recommendations for Prevention.

PURPOSE OF REVIEW: The manuscript reviews the extant literature on suicide-related thoughts and behaviors among youth and young adults with pediatric diabetes. This evidence is presented within the context of current theories of the etiology of suicidal behavior to highlight how diabetes may contribute to suicide risk, and to support providers in understanding the interplay between pediatric diabetes and suicide risk. The manuscript also reviews evidence-based approaches to suicide prevention suitable for use in pediatric healthcare settings, with suggestions for their application to this unique population. RECENT FINDINGS: Several recent studies identify heightened rates of suicidal ideation, suicide attempts, and suicide among youth and young adults with pediatric diabetes, as compared with their peers without diabetes. Evidence-based suicide prevention approaches frequently emphasize the importance of reducing suicidal youths' access to potentially lethal means for suicidal behavior. This approach may require special considerations for youth with pediatric diabetes, due to their need to carry sufficient quantities of insulin and the dangers of inaccurate insulin dosing and/or overdose. Suggestions for suicide prevention for this population include risk screening as part of routine diabetes care, early prevention, education for youth and families, and provider awareness of risk factors, warning signs, and implications for diabetes care. Youth and young adults with diabetes reported elevated rates of suicide-related behaviors as compared with their peers without diabetes. Existing suicide prevention approaches may require substantial adaptation for use with youth and young adults with diabetes. Further research is needed to examine how to best prevent suicidal behaviors among this population.

The Incidence of Erosive Esophagitis as a Complication of Pediatric Diabetic Ketoacidosis.

INTRODUCTION: Gastrointestinal (GI) symptoms commonly occur during diabetic ketoacidosis (DKA) and typically resolve with treatment. However, GI complications can persist after DKA resolves. The incidence of upper GI bleeding during DKA in adults has been described, with erosive esophagitis one of the most common lesions. The incidence of GI bleeding or erosive esophagitis in children with DKA has not been previously reported. We performed a retrospective chart review of DKA admissions in children 0 to <18 years with type 1 diabetes mellitus (T1DM) at a pediatric hospital between January 2009 and July 2016. Among 395 episodes of DKA over 7.5 years, erosive esophagitis occurred during two DKA admissions (0.5%) and there were no episodes of GI bleeding. Case presentations. Both episodes of erosive esophagitis occurred in adolescent males with known T1DM who presented with severe DKA. Both developed odynophagia after resolution of DKA and were readmitted for DKA recurrence. Upper endoscopy for both patients showed erosive esophagitis. Biopsies were negative for infection, though candida was found during one patient's endoscopy. Both had resolution of their esophagitis symptoms with medication management; neither has had recurrence. CONCLUSION: Erosive esophagitis, a rare complication of pediatric DKA, can manifest with odynophagia or substernal chest pain. This complication can lead to DKA recurrence, likely due to increased insulin resistance from inflammation and pain and from reduced oral intake and insulin administration. Patients with odynophagia associated with DKA should be monitored closely to allow timely evaluation and treatment of esophagitis.

Diabetes Curriculum for Pediatric Endocrine Fellowship Utilizing Modified Team-Based Learning.

Introduction: While type 1 diabetes is frequently encountered clinically in pediatric endocrinology fellowship training, other types of diabetes may only be encountered in educational settings. Adult learners learn best through knowledge application, but to date there are no published curricula utilizing application educational strategies for all forms of diabetes. Methods: We utilized a team-based learning (TBL) approach to create four modules on different types of diabetes: type 1 diabetes, type 2 diabetes, neonatal diabetes, and maturity-onset diabetes of the young. We divided our fellows (all training years, n = 11) into two teams and delivered four separate, 90-minute sessions. To emphasize the application of knowledge, we modified the format to combine the readiness assurance test (RAT) with application problem (APP) questions. The combined RAT/APP questions were answered by individuals and teams. We analyzed scores from individual and team tests and evaluated each module. Additionally, we acquired subjective data from the fellows regarding their experiences. Results: Teams outperformed individuals on the tests, as expected (94% vs. 76% correct questions, respectively). All the fellows agreed that the sessions should be included permanently. Additionally, all agreed the sessions helped them apply knowledge. Subjectively, the fellows were very engaged and lively during the sessions and felt the sessions were feasible as implemented. Discussion: TBL can be a valuable educational strategy to increase the application of knowledge for diabetes in pediatric endocrinology fellows. Future studies examining the use of this strategy to increase critical thinking skills and knowledge retention in the long-term would be useful.

PARTIAL HOSPITALIZATION: AN INTERVENTION FOR YOUTH WITH POORLY CONTROLLED DIABETES MELLITUS.

Objective: To examine the efficacy of an integrated medical/psychiatric partial hospitalization program (PHP) to improve glycemic control in youth with both diabetes mellitus and mental health disorders. Methods: This retrospective chart review is of patients admitted to a PHP between 2005-2015 with concerns about diabetes mellitus care. Clinical characteristics, laboratory data, diabetic ketoacidosis hospitalizations, and outpatient clinic visit frequency were collected from the year prior to the year after PHP admission. Results: A total of 43 individuals met inclusion criteria: 22 (51%) were female, 40 (93%) had type 1 diabetes, the mean age was 15.2 ± 2.3 years, and the mean diabetes mellitus duration was 4.6 ± 3.6 years. Of those individuals, 35 of these patients had hemoglobin A1c (HbA1c) data available at baseline, 6 months, and 1 year after PHP. The average HbA1c before PHP admission was 11.3 ± 2.3% (100.5 ± 25 mmol/mol), and decreased to 9.2 ± 1.3% (76.7 ± 14.8 mmol/mol) within 6 months of PHP admission (P<.001). The average HbA1c 1 year after PHP was 10.7 ± 1.7 % (93.3 ± 19.1 mmol/mol). Overall, 24 patients (68%) had lower HbA1c, and 75% of those with improvement maintained an HbA1c reduction of ≥1% (≥10 mmol/mol) at 1 year compared to before PHP. Conclusion: Most patients demonstrated improved glycemic control within 6 months of PHP admission, and many of those maintained a ≥1% (≥10 mmol/mol) reduction in HbA1c at 1 year following PHP admission. This program may represent a promising intervention that could serve as a model for intensive outpatient management of youth with poorly controlled diabetes mellitus. Abbreviations: ADA = American Diabetes Association; DKA = diabetic ketoacidosis; EMR = electronic medical record; HbA1c = hemoglobin A1c; ICD-9 = International Classification of Diseases, 9th revision; PHP = partial hospitalization program.

Nephrolithiasis: A complication of pediatric diabetic ketoacidosis.

OBJECTIVE: To determine the frequency of nephrolithiasis as a complication of diabetic ketoacidosis (DKA) in pediatrics. METHODS: We performed a retrospective chart review of patients with DKA admitted to a pediatric hospital between January 2009 and July 2016. We identified patients with nephrolithiasis during admission for DKA. RESULTS: We identified 395 episodes of DKA over 7.5 years. Nephrolithiasis developed as a complication of DKA in 3 of those admissions (0.8%). All three patients with nephrolithiasis were males with new onset type 1 diabetes, aged 11 to 16.5 years. They all developed symptoms of nephrolithiasis after transition to subcutaneous insulin. One patient had subsequent worsening acidosis that required an additional 24 hours of IV insulin administration. CONCLUSIONS: Nephrolithiasis is a rare complication of pediatric DKA, and should be considered in children with DKA who develop hematuria, flank pain, or suprapubic pain. Nephrolithiasis can increase insulin resistance due to increased pain and inflammation, so these patients should be monitored closely for recurrence of DKA. As patients with diabetes have increased risk of chronic kidney disease and nephrolithiasis can cause kidney injury, risk factors for nephrolithiasis should be identified and addressed to avoid subsequent kidney damage.

Severe Short Stature in an Adolescent Male with Prader-Willi Syndrome and Congenital Adrenal Hyperplasia: A Therapeutic Conundrum.

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency results in excess androgen production which can lead to early epiphyseal fusion and short stature. Prader-Willi syndrome (PWS) is a genetic disorder resulting from a defect on chromosome 15 due to paternal deletion, maternal uniparental disomy, or imprinting defect. Ninety percent of patients with PWS have short stature. In this article we report a patient with simple-virilizing CAH and PWS who was overtreated with glucocorticoids for CAH and not supplemented with growth hormone for PWS, resulting in a significantly short adult height.

Glycogen storage disease type IX and growth hormone deficiency presenting as severe ketotic hypoglycemia.

BACKGROUND: Glycogen storage disease (GSD) type IX and growth hormone (GH) deficiency cause ketotic hypoglycemia via different mechanisms and are not known to be associated. We describe a patient presenting with severe ketotic hypoglycemia found to have both GSD IX and isolated GH deficiency. CASE PRESENTATION: A 3-year-and-11-month-old boy with a history of prematurity, autism, developmental delay, seizures, and feeding difficulty was admitted for poor weight gain and symptomatic hypoglycemia. He was nondysmorphic, with a height of 93.8 cm (2%, -1.97 SDS), and has no hepatomegaly. He developed symptomatic hypoglycemia, with a serum glucose level of 37 mg/dL after 14 h of fasting challenge. Critical sample showed a GH of 0.24 ng/mL. GH provocative stimulation testing was done with a peak GH of 2.8 ng/mL. Brain magnetic resonance imaging showed a hypoplastic pituitary gland. Given the clinical symptoms, suspicion for mitochondrial disease was high. Dual Genome Panel by Massively Parallel Sequencing revealed a hemizygous variant c.721A>G (p1241V) in the X-linked PHKA2 gene, a causative gene for GSD IX. Red blood cell PhK enzyme activity testing was low, supporting the diagnosis. CONCLUSIONS: Given the patient's developmental delays that were not explained by GH deficiency alone, further investigation showed two unrelated conditions resulting in deranged metabolic adaptation to fasting leading to severe hypoglycemia.

Comparison of pediatric patients with status epilepticus lasting 5-29 min versus ≥30 min.

The most common thresholds for considering prolonged seizures as status epilepticus (SE) are 5 and 30 min. It is unknown whether these different thresholds (5 or 30 min) identify patient populations with different electroclinical characteristics. We compared the characteristics of patients with SE lasting 5-29 min (SE5-29) with those with SE lasting ≥30 min (SE≥30). Inclusion criteria were the following: 1) 1 month to 21 years of age at the time of SE, 2) convulsive seizures, and 3) seizure duration ≥5 min. Exclusion criteria were the following: 1) exclusively neonatal seizures, 2) psychogenic nonepileptic seizures, or 3) incomplete information about seizure duration. Four hundred forty-five patients (50.1% male) with a median (p25-p75) age at SE of 5.5 (2.8-10.5) years were enrolled. Status epilepticus lasted for 5-29 min in 296 (66.5%) of subjects and for ≥30 min in 149 (33.5%). Patients with SE≥30 were younger than the patients with SE5-29 at the time of seizure onset (median: 1 versus 2.1 years, p=0.0007). Status epilepticus as the first seizure presentation was more frequent in patients with SE≥30 (24.2% versus 12.2%, p=0.002). There was a tendency towards a higher rate of abnormalities in the magnetic resonance imaging at baseline in patients with SE≥30 (70.5% versus 57.1%, p=0.061). Differences were not detected in seizure frequency, seizure types, presence of developmental delay, and electroencephalogram abnormalities at baseline. In the pediatric population, SE thresholds of either 5 or 30 min identify groups of patients with very similar electroclinical characteristics, which may influence future definitions of pediatric SE.