Medication-induced hyperglycemia is a frequently encountered clinical problem in children. The intent of this review of medications that cause hyperglycemia and their mechanisms of action is to help guide clinicians in prevention, screening and management of pediatric drug-induced hyperglycemia. We conducted a thorough literature review in PubMed and Cochrane libraries from inception to July 2019. Although many pharmacotherapies that have been associated with hyperglycemia in adults are also used in children, pediatric-specific data on medication-induced hyperglycemia are scarce. The mechanisms of hyperglycemia may involve β cell destruction, decreased insulin secretion and/or sensitivity, and excessive glucose influx. While some medications (eg, glucocorticoids, L-asparaginase, tacrolimus) are markedly associated with high risk of hyperglycemia, the association is less clear in others (eg, clonidine, hormonal contraceptives, amiodarone). In addition to the drug and its dose, patient characteristics, such as obesity or family history of diabetes, affect a child’s risk of developing hyperglycemia. Identification of pediatric patients with increased risk of developing hyperglycemia, creating strategies for risk reduction, and treating hyperglycemia in a timely manner may improve patient outcomes.

Objective Puberty‐induced insulin resistance is considered critical in the pathogenesis of type 2 diabetes (T2D) in youth. The development of T2D before puberty suggests distinct risk factors and pathophysiology but, because of its rarity, this has not been well studied. We aimed to describe the clinical characteristics of children with T2D diagnosed before the onset of puberty. Research design and methods We retrospectively studied all children with autoantibody‐negative T2D and available pubertal development assessment seen at our center between July 2016 and July 2019, and compared characteristics of those at Tanner stage I (prepubertal, n = 35) versus those at Tanner II–V of pubertal development (n = 341). Results At T2D diagnosis, prepubertal children compared with those at Tanner II–V had higher body mass index z‐score (p = 0.003) and higher C‐peptide (p = 0.003) (while glucose levels were not significantly different), with differences retaining significance after adjustment for glucose, race/ethnicity and sex. Dyslipidemia occurred in 100% of prepubertal children versus 89.7% of those diagnosed later (p = 0.036). Of the prepubertal children diagnosed under age 10 (n = 13), 69.2% were female, 100% racial/ethnic minority, 100% had obesity with history of dyslipidemia and none with diabetic ketoacidosis. Conclusions T2D, although rarely, can develop before puberty. Children with T2D diagnosed in the prepubertal period have more severe obesity, greater insulin resistance, and more frequent dyslipidemia than older youth. These findings suggest that children with prepubertal T2D are at increased risk for associated morbidity compared with older youth and underscore the significance of interventions to prevent and treat obesity in early childhood.

The incidence of diabetes, both type 1 and type 2, is increasing. Health outcomes in pediatric diabetes are currently poor, with trends indicating that they are worsening. Minority racial/ethnic groups are disproportionately affected by suboptimal glucose control and have a higher risk of acute and chronic complications of diabetes. Correct clinical management starts with timely and accurate classification of diabetes, but in children this is becoming increasingly challenging due to high prevalence of obesity and shifting demographic composition. The growing obesity epidemic complicates classification by obesity's effects on diabetes. Since the prevalence and clinical characteristics of diabetes vary among racial/ethnic groups, migration between countries leads to changes in the distribution of diabetes types in a certain geographical area, challenging the clinician's ability to classify diabetes. These challenges must be addressed to correctly classify diabetes and establish an appropriate treatment strategy early in the course of disease for all. This may be the first step in improving diabetes outcomes across racial/ethnic groups. This review will discuss the pitfalls in the current diabetes classification scheme that is leading to increasing overlap between diabetes types and heterogeneity within each type. It will also present proposed alternative classification schemes and approaches to understanding diabetes type that may improve the timely and accurate classification of pediatric diabetes type. K E Y W O R D S delayed diagnosis, diabetes complications, diabetes mellitus, MODY, pediatrics 1 | INTRODUCTION Diabetes is one of the most common chronic diseases in pediatric populations, and, if poorly managed, can result in acute and long-term complications that can significantly affect childhood and reduce productivity in adult years. 1 The incidences of pediatric type 1 diabetes (T1D) and type 2 diabetes (T2D) are increasing for reasons not completely understood, but this may in part be due to the increasing incidence of obesity. 1 The incidences of pediatric T1D and T2D have increased globally. 2-7 In the United States, at the current rate, the number of T1D and T2D cases could triple and quadruple to almost 600 000 and 85 000 US children, respectively, by 2050. 8 Current trends suggest that this increase will disproportionately affect non-Caucasian groups. 9 In the United Kingdom, South Asians are the group with the most dramatic increase. 4 While lower socioeconomic status is a risk factor for pediatric T2D in developed countries, in emerging countries, children from the most affluent families are at highest risk. 6,10 We and others demonstrated that elevated body mass index (BMI), in addition to its well-known association with T2D, is associated with accelerated progression to T1D in children 11,12 and adults. 13 Obesity-induced insulin resistance may render insufficient the already compromised insulin secretion in individuals with islet autoimmunity and thus, trigger clinical diabetes. In addition, obesi...