Diabetic ketoacidosis (DKA) is a life-threatening complication of type 1 diabetes. Our objective was to determine if children with severe DKA without alteration in mental status can be managed safely on a general children's medical unit.Single center retrospective study of 191 patient encounters among 168 children admitted to the children's medical unit (CMU) at Primary Children's Hospital between 2007 and 2017 with severe DKA (pH <7.1 and/or bicarbonate <5 mmol/L). Chart review identified complications including death, transfer to the intensive care unit (ICU), incidence of cerebral edema, and hypoglycemia. We compared patients requiring ICU transfer with those who did not with respect to demographics, laboratory findings at presentation, therapeutic interventions, length of stay, and cost.Of 191 patient encounters, there were 0 deaths (0%, 95% CI 0-2.4%), 22 episodes of alteration of mental status concerning for developing cerebral edema (11.5%, 95% CI 7.7-16.9%), 19 ICU transfers (10%, 95% CI 6.4-15.1%), and 7 episodes of hypoglycemia (3.7%, 95% CI 1.6-7.5%). ICU transfer was associated lower initial pH (7.03 ± 0.06 vs. 7.07 ± 0.07, p<0.05), increased length of stay (3.0 ± 0.8 vs. 2.2 ± 0.9 days, p<0.05), and increased cost of hospitalization (mean ± SD $8,073 ± 2,042 vs. $5,217 ± 1,697, p<0.05).The majority of children with severe DKA without alteration in mental status can be managed safely on a medical unit. Implementing a pH cutoff may identify high-risk patients that require ICU level of care.
Childhood obesity has steadily become a contemporary epidemic with serious public health implications.1 Approximately 70% of children with obesity will remain obese in adulthood.2 Obesity is a risk factor for development of atherosclerosis and type 2 diabetes mellitus (T2DM),3 and its prevention and management represents a priority for pediatric primary care providers. This underscores the need for evidence-based interventions for children and adolescents with obesity, including pharmacotherapy.4Metformin is US Food and Drug Administration (FDA) approved for use in children 10 years of age and older with T2DM and has been used off label to achieve weight loss in children. In the current issue of Pediatrics, Masarwa et al5 present a systematic review of the safety and efficacy of metformin use from randomized controlled trials (RCTs) in children and adolescents. The authors demonstrated that metformin therapy resulted in modest benefits in reduction of BMI in those with obesity. Among the 14 RCTs in which BMI was reported, metformin was modestly efficacious at decreasing BMI (range of mean changes: −2.70 to 1.30) compared with a placebo (−1.12 to 1.90). As pointed out by the authors, the results across the studies were heterogeneous, with 11 RCTs suggesting that it decreased BMI, whereas 3 RCTs revealed an increase in BMI. Among the 7 RCTs in which a BMI z score was reported, metformin consistently resulted in a decrease in the BMI z score (range of mean changes: −0.37 to −0.03) when compared with a placebo (−0.22 to 0.15), with the largest decrease in BMI z score observed in children and adolescents with nonalcoholic fatty liver disease. Among the 11 RCTs in which insulin resistance was examined, metformin resulted in modest but favorable effects on insulin resistance. Metformin therapy, however, was associated with a doubling of the rate of gastrointestinal adverse events compared with a placebo. This brings up the issue of whether metformin is a reasonable adjunct to behavioral and lifestyle modifications for treatment of childhood obesity.Options for weight management in pediatric patients are significantly limited.6,7 Lifestyle modification therapy, which incorporates nutritional, physical activity, and behavior modification, has been the mainstay of management, for both children and adults. Although successful weight loss is underpinned by lifestyle modification, achieving durable weight loss by this approach is challenging. The biology of weight gain and the regulation of appetite, satiety, and energy use through basal metabolism and exercise are tightly controlled by central and peripheral mechanisms that undermine the ability to lose weight. Therefore, additional therapies, such as pharmacologic treatments, are attractive options before proceeding to bariatric surgery.Several antiobesity drugs have been approved by the FDA for use among adult patients with obesity, and numerous clinical trials have been conducted to support their use.8 In children, the only FDA-approved pharmacotherapies for obesity are orlistat and liragutide in persons 12 and older and phenteremine in persons 16 years of age and older. Orlistat has been associated with modest BMI reduction but may cause intolerable gastrointestinal side effects and possible fat-soluble vitamin deficiency. Phentermine is approved for short-term therapy only and may increase heart rate and blood pressure and cause irritability and insomnia. Long-term studies of its use in children are not available. Glucagon-like peptide-1 receptor agonist, such as liraglutide, is a second-line treatment for T2DM in adolescents. Liragutide is approved for obesity in adults since 2014 and has shown weight loss in obese adolescents in a RCT.7 About 43% of liragutide treated patients and 18% of placebo patients had a 5% reduction in BMI and in 26% and 8% respectively, a reduction of 10% was seen. It was recently approved by the FDA for treatment of pediatric obesity in December 2020. The dose for obesity differs from the dose for T2DM. It is approved for use in adolescents >12 years of age with a body weight of >60 kg and a BMI for age and sex corresponding to 30 kg/m2 or greater in adults, as an adjunct to reduced calorie diet and increased physical activity. Its use is limited by the need for daily subcutaneous injections and high frequency of gastrointestinal side effects and high cost.The combination of topiramate and phentermine is available in adults for weight management. Small studies in children of topiramate alone suggest meaningful weight loss may occur, but its use has been associated with cognitive dysfunction.9 Other weight loss agents approved in adults include lorcaserin, a 5-hydroxytryptamine receptor 2C agonist, and naltrexone and bupropion. Setmelanotide, a melanocortin-4-receptor agonist was recently approved by the FDA for children >6 years with monogenic obesity due to three rare genetic conditions: pro-opiomelanocortin (POMC) deficiency, proprotein subtilisin/kexin type 1 (PCSK1) deficiency, and leptin receptor (LEPR) deficiency. There are several other drugs that are in pediatric trials for monogenic obesity.10Understandably, those caring for children with moderate or severe obesity are looking for adjuncts to lifestyle modification to promote weight loss. In a recent study, Borzutzky et al4 indicated that antiobesity pharmacotherapy prescribing appears to be increasing among providers treating pediatric obesity despite the lack of FDA approval for such drugs in youth. According to the study, metformin was the most prescribed drug for obesity in 2014, and topiramate was the most prescribed drug for obesity in 2017.Metformin reduces hepatic glucose production, decreases intestinal glucose absorption, and increases peripheral insulin sensitivity and may reduce appetite by raising glucagon-like peptide-1 levels. Its precise mechanism of action for weight reduction is not completely understood. It has a reasonable safety profile, and its gastrointestinal side effects can be minimized by slowly increasing the dosage. The sustainability of metformin effects on weight loss is unknown, such that most authors recommend that metformin be reserved for use in T2DM and, perhaps, polycystic ovary syndrome in youth.Ideally, children with obesity should be entered into a clinical trial rather than placed on an off-label medication. Metformin is a low-cost option and may provide modest clinical benefit for weight loss with minimal side effects. If lifestyle modification has been pursued but has achieved minimal weight loss, it may be reasonable to try an agent such as metformin as adjunctive therapy. Many gaps remain in the knowledge of effective and durable therapies for childhood obesity, which is more prevalent in families and neighborhoods with low socioeconomic status.11 We clearly need novel cost-effective approaches and more clinical trials in children to help reduce the burden of this disease on our youth and on public health in general.
A Pediatric Endocrine Society (PES) Drugs and Therapeutics Committee workgroup sought to determine the prescribing practices of pediatric endocrinologists when treating children <10 years of age with congenital adrenal hyperplasia (CAH). Our workgroup administered a 32-question online survey to PES members. There were 187 respondents (88.9% attending physicians), mostly from university-affiliated clinics (~80%). Ninety-eight percent of respondents prescribed the short-acting glucocorticoid hydrocortisone to treat young children, as per the Endocrine Society CAH Guidelines, although respondents also prescribed long-acting glucocorticoids such as prednisolone suspension (12%), prednisone tablets (9%), and prednisone suspension (6%). Ninety-seven percent of respondents indicated that they were likely/very likely to prescribe hydrocortisone in a thrice-daily regimen, as per CAH Guidelines, although 19% were also likely to follow a twice-daily regimen. To achieve smaller doses, using a pill-cutter was the most frequent method recommended by providers to manipulate tablets (87.2%), followed by dissolving tablets in water (25.7%) to create a daily batch (43.7%) and/or dissolving a tablet for each dose (64.6%). Thirty-one percent of providers use pharmacy-compounded hydrocortisone suspension to achieve doses of <2.5 mg. Our survey shows that practices among providers in the dosing of young children with CAH vary greatly and sometimes fall outside of the CAH Guidelines—specifically when attempting to deliver lower, age-appropriate hydrocortisone doses.
Prevalence of metabolic syndrome in children and adolescents is increasing, in parallel with the increasing trends in obesity rates. Varying definitions of this syndrome have hindered the development of a consensus for the diagnostic criteria in the pediatric population. While pathogenesis of metabolic syndrome is not completely understood, insulin resistance and subsequent inflammation are thought to be among its main mechanistic underpinnings. Overweight and obesity are cardinal features, along with abnormal glucose metabolism, dyslipidemia, and hypertension. Other disorders associated with metabolic syndrome include fatty liver, polycystic ovarian syndrome (PCOS), and pro-inflammatory states. Prevention and management of this condition can be accomplished with lifestyle modifications, behavioral interventions, pharmacological and surgical interventions as needed.
Diabetic retinopathy is a complication of diabetes that affects the blood vessels of the retina. The majority of patients with diabetic retinopathy exhibit background retinopathy. In approximately 10% of patients, background retinopathy will progress to sight-threatening retinopathy. The aims of our study were to measure the prevalence of retinopathy among our population and to assess the optimal time of screening children and adolescents with type 1 diabetes.
Health insurance coverage type differs significantly by socioeconomic status and racial group in the United States. The aim of this study was to determine whether publicly insured children and young adults with type 1 diabetes were more likely to experience adverse outcomes compared with privately insured patients with acute coronavirus disease 2019 (COVID-19) infections.Data from 619 patients with previously established type 1 diabetes who were <24 years of age with acute COVID-19 infections were analyzed from the T1D Exchange COVID-19 surveillance registry. Data for the registry was collected from 52 endocrinology clinics across the United States using an online survey tool. Each site completed the survey using electronic health record data between April 2020 and December 2021.Of the 619 patients included in this study, 257 had public insurance and 362 had private insurance. Of the 257 publicly insured patients with COVID-19, 57 reported severe adverse outcomes (22%), defined as diabetic ketoacidosis (DKA) or severe hypoglycemia. In comparison, there were 25 reported adverse outcomes (7%) among the 362 privately insured patients.Our data reveal high rates of hospitalization and DKA among publicly insured racial/ethnic minority children and young adults with type 1 diabetes and COVID-19.
Identification of modifiable risk factors, including genetic and acquired disorders of lipid and lipoprotein metabolism, is increasingly recognized as an opportunity to prevent premature cardiovascular disease (CVD) in at-risk youth. Pediatric endocrinologists are at the forefront of this emerging public health concern and can be instrumental in beginning early interventions to prevent premature CVD-related events during adulthood.
OBJECTIVE Innate immune responses may be involved in the earliest phases of type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS To test whether blocking innate immaune cells modulated progression of the disease, we randomly assigned 273 individuals with stage 1 T1D to treatment with hydroxychloroquine (n = 183; 5 mg/kg per day to a maximum of 400 mg) or placebo (n = 90) and assessed whether hydroxychloroquine treatment delayed or prevented progression to stage 2 T1D (i.e., two or more islet autoantibodies with abnormal glucose tolerance). RESULTS After a median follow-up of 23.3 months, the trial was stopped prematurely by the data safety monitoring board because of futility. There were no safety concerns in the hydroxychloroquine arm, including in annual ophthalmologic examinations. Preplanned secondary analyses showed a transient decrease in the glucose average area under the curve to oral glucose in the hydroxychloroquine-treated arm at month 6 and reduced titers of anti-GAD and anti-insulin autoantibodies and acquisition of positive autoantibodies in the hydroxychloroquine arm (P = 0.032). CONCLUSIONS We conclude that hydroxychloroquine does not delay progression to stage 2 T1D in individuals with stage 1 disease. Drug treatment reduces the acquisition of additional autoantibodies and the titers of autoantibodies to GAD and insulin.
