Approach to the Patient: Youth-Onset Type 2 Diabetes.

Youth-onset type 2 diabetes is a growing epidemic with a rising incidence worldwide. Although the pathogenesis and diagnosis of youth-onset type 2 diabetes are similar to adult-onset type 2 diabetes, youth-onset type 2 diabetes is unique, with greater insulin resistance, insulin hypersecretion, and faster progression of pancreatic beta cell function decline. Individuals with youth-onset type 2 diabetes also develop complications at higher rates within short periods of time compared to adults with type 2 diabetes or youth with type 1 diabetes. The highest prevalence and incidence of youth-onset type 2 diabetes in the United States is among youth from minoritized racial and ethnic groups. Risk factors include obesity, family history of type 2 diabetes, comorbid conditions and use of medications associated with insulin resistance and rapid weight gain, socioeconomic and environmental stressors, and birth history of small-for-gestational-age or pregnancy associated with gestational or pregestational diabetes. Patients with youth-onset type 2 diabetes should be treated using a multidisciplinary model with frequent clinic visits and emphasis on addressing of social and psychological barriers to care and glycemic control, as well as close monitoring for comorbidities and complications. Intensive health behavior therapy is an important component of treatment, in addition to medical management, both of which should be initiated at the diagnosis of type 2 diabetes. There are limited but growing pharmacologic treatment options, including metformin, insulin, glucagon-like peptide 1 receptor agonists, and sodium-glucose cotransporter 2 inhibitors. Although long-term outcomes are not fully known, metabolic/bariatric surgery in youth with type 2 diabetes has led to improved cardiometabolic outcomes.

The impact of fear of hypoglycaemia on sleep in adolescents with type 1 diabetes.

AIMS: Fear of hypoglycaemia (FOH) can contribute to impaired sleep for adults with type 1 diabetes (T1D) and parents of children with T1D, although it is unknown how FOH may affect sleep for adolescents with T1D. This study examines the relationship between adolescent FOH and sleep and assessed the influences of continuous glucose monitor (CGM) and insulin pump use. METHODS: Adolescents ages 14-18 years with T1D completed questionnaires evaluating FOH (Child Hypoglycemia Fear Survey) and sleep (Pittsburgh Sleep Quality Index, PSQI). Analyses included linear and logistic regression, t-tests and Fisher's exact tests. RESULTS: Participants included 95 adolescents (52 female) with a median (IQR) age of 16.5 (15.3-17.7) years and a T1D duration of 5.7 (2.5-9.6) years. Analyses showed increased FOH-Worry subscale scores were associated with reduced sleep duration (ß = -0.03, p = 0.042, adjusting for BMI z-score, race and ethnicity) and increased sleep disturbances (OR = 1.1, p = 0.038, adjusting for race and ethnicity). Frequent CGM users had longer sleep duration (average 7.5 h) compared with infrequent or non-CGM users (average = 6.8 h; p = 0.029), and pump users had overall improved sleep health as determined by PSQI score (p = 0.019). Technology use did not have significant interactions in the relationships between FOH and sleep duration or sleep disturbances. CONCLUSIONS: Worrying about hypoglycaemia was associated with impaired sleep for adolescents with T1D. Diabetes technology users have some sleep improvements, but CGM and pump use do little to alter the relationship between FOH and sleep outcomes.

Text Messages and Financial Incentives to Increase Physical Activity in Adolescents With Prediabetes and Type 2 Diabetes: Web-Based Group Interviews to Inform Intervention Design.

BACKGROUND: Physical activity is a major component of treatment for adolescents with obesity and prediabetes or type 2 diabetes; however, sedentary behavior remains pervasive. An SMS text message-based intervention paired with financial incentives may be an effective way to promote physical activity in this population. OBJECTIVE: This study aims to obtain end-user feedback on SMS text message content and assess the acceptability of a planned SMS text messaging intervention with financial incentives to motivate youth with prediabetes or type 2 diabetes to increase physical activity. METHODS: Adolescents with overweight or obesity and prediabetes or type 2 diabetes who attended a large academic pediatric endocrinology clinic were recruited to participate in group interviews (2-4/group) via videoconferencing. Participants were asked to share their thoughts on the use of SMS text messages and financial incentives to remind and motivate them to be more physically active. They rated and provided feedback on specific messages to be used in clinical trials. Participants were also asked about their personal experience with rewards to motivate behavior change and their anticipated reactions to rewards provided for goal attainment (gain-framing) versus those provided and then taken away if a goal was not met (loss-framing). The interviews were conducted by 2 trained interviewers and a note-taker. Content analysis was used to explore themes. RESULTS: Group interviews were completed with 20 participants (11/20, 55% women; 15/20, 75% with type 2 diabetes; 5/20, 25% with prediabetes) with a mean age of 15 (SD 1; range 12-18) years and a mean BMI of 41 (SD 5) kg/m2 (all >95th percentile for age and sex). Most participants were non-Hispanic Black (14/20, 70%) and 10% (2/20) were Hispanics. Participants frequently cited near-continuous smartphone use and agreed that SMS text messages would serve as good reminders to be physically active, but the consensus about the need for short messages was strong. Favorable content included references to what they were likely to be doing when messages were sent (eg, homework or watching television) and messages that were upbeat or informative. Specific physical activity suggestions were rated favorably. Attitudes toward financial incentives varied, with differing opinions about whether loss-framed incentives would be motivating or discouraging. Many participants highlighted the role of intrinsic, rather than extrinsic, motivation in achieving and sustaining behavior change. CONCLUSIONS: The engagement of adolescents with obesity and diabetes or prediabetes allowed for the refinement of SMS text messages for our planned intervention, with an emphasis on short, upbeat, relatable, and informative messages. Although an SMS text messaging intervention using financial incentives to motivate youth with prediabetes or type 2 diabetes to be more physically active is theoretically acceptable, the impact on actual activity levels in this population requires prospective evaluation in a clinical trial.

Obesity and Health-Related Quality of Life in Children Hospitalized for Acute Respiratory Illness.

OBJECTIVES: Obesity has rapidly become a major problem for children that has adverse effects on respiratory health. We sought to assess the impact of obesity on health-related quality of life (HRQOL) and hospital outcomes for children hospitalized with asthma or pneumonia. METHODS: In this multicenter prospective cohort study, we evaluated children (aged 2-16 years) hospitalized with an acute asthma exacerbation or pneumonia between July 1, 2014, and June 30, 2016. Subjects or their family completed surveys for child HRQOL (PedsQL Physical Functioning and Psychosocial Functioning Scales, with scores ranging from 0 to 100) on hospital presentation and 2-6 weeks after discharge. BMI categories were defined as normal weight, overweight, and obesity on the basis of BMI percentiles for age and sex per national guidelines. Multivariable regression models were used to examine associations between BMI category and HRQOL, length of stay, and 30-day reuse. RESULTS: Among 716 children, 82 (11.4%) were classified as having overweight and 138 (19.3%) as having obesity. For children hospitalized with asthma or pneumonia, obesity was not associated with worse HRQOL at presentation or 2-6 weeks after discharge, hospital length of stay, or 30-day reuse. CONCLUSIONS: Nearly 1 in 3 children seen in the hospital for an acute asthma exacerbation or pneumonia had overweight or obesity; however, among the population of children in our study, obesity alone does not appear to be associated with worse HRQOL or hospital outcomes.

Real-world treatment escalation from metformin monotherapy in youth-onset Type 2 diabetes mellitus: A retrospective cohort study.

BACKGROUND: Due to high rates of comorbidities and rapid progression, youth with Type 2 diabetes may benefit from early and aggressive treatment. However, until 2019, the only approved medications for this population were metformin and insulin. OBJECTIVE: To investigate patterns and predictors of treatment escalation within 5 years of metformin monotherapy initiation for youth with Type 2 diabetes in clinical practice. SUBJECTS: Commercially-insured patients with incident youth-onset (10-18 years) Type 2 diabetes initially treated with metformin only. METHODS: Retrospective cohort study using a patient-level medical claims database with data from 2000 to 2020. Frequency and order of treatment escalation to insulin and non-insulin antihyperglycemics were determined and categorized by age at diagnosis. Cox proportional hazards regression was used to evaluate potential predictors of treatment escalation, including age, sex, race/ethnicity, comorbidities, complications, and metformin adherence (medication possession ratio ≥ 0.8). RESULTS: The cohort included 829 (66% female; median age at diagnosis 15 years; 19% Hispanic, 17% Black) patients, with median 2.9 year follow-up after metformin initiation. One-quarter underwent treatment escalation (n = 207; 88 to insulin, 164 to non-insulin antihyperglycemic). Younger patients were more likely to have insulin prescribed prior to other antihyperglycemics. Age at diagnosis (HR 1.14, 95% CI 1.07-1.21), medication adherence (HR 4.10, 95% CI 2.96-5.67), Hispanic ethnicity (HR 1.83, 95% CI 1.28-2.61), and diabetes-related complications (HR 1.78, 95% CI 1.15-2.74) were positively associated with treatment escalation. CONCLUSIONS: In clinical practice, treatment escalation for pediatric Type 2 diabetes differs with age. Off-label use of non-insulin antihyperglycemics occurs, most commonly among older adolescents.

Sex differences in childhood sleep and health implications.

CONTEXT: Sleep is critical for optimal childhood metabolic health and neurodevelopment. However, there is limited knowledge regarding childhood sex differences in sleep, including children with neurodevelopmental disorders, and the impact of such differences on metabolic health. OBJECTIVE: To evaluate if sex differences in childhood sleep exist and if sleep associates with metabolic health outcomes equally by sex. Using autism spectrum disorder (ASD) as a case study, we also examine sleep sex differences in children with a neurodevelopmental disorder. METHODS: A narrative review explored the literature focussing on sex differences in childhood sleep. RESULTS: Sex differences in sleep were not detected among pre-adolescents. However, female adolescents were more likely to report impaired sleep than males. Childhood obesity is more common in males. Shorter sleep duration may be associated with obesity in male pre-adolescents/adolescents; although findings are mixed. ASD is male-predominant; yet, there was an indication that pre-adolescent female children with ASD had more impaired sleep. CONCLUSION: Sex differences in sleep appear to emerge in adolescence with more impaired sleep in females. This trend was also observed among pre-adolescent female children with ASD. Further research is needed on sex differences in childhood sleep and metabolic health and the underlying mechanisms driving these differences.

Pediatric Type 2 Diabetes: Not a Mini Version of Adult Type 2 Diabetes.

Pediatric type 2 diabetes mellitus (T2DM) is increasing in incidence, with risk factors including obesity, puberty, family history of T2DM in a first-degree or second-degree relative, history of small-for-gestational-age at birth, child of a gestational diabetes pregnancy, minority racial group, and lower socioeconomic status. The pathophysiology of T2DM consists of insulin resistance and progression to pancreatic beta-cell failure, which is more rapid in pediatric T2DM compared with adult T2DM. Treatment options are limited. Treatment failure and nonadherence rates are high in pediatric T2DM; therefore, early diagnosis and treatment and new pharmacologic options and/or effective behavioral interventions are needed.

Pediatric provider perspectives and practices regarding health policy discussions with families: a mixed methods study.

BACKGROUND: Advocacy regarding child health policy is a core tenet of pediatrics. Previous research has demonstrated that most pediatric providers believe collective advocacy and political involvement are essential aspects of their profession, but less is known about how pediatric providers engage with families about policy issues that impact child health. The objectives of this study were to examine providers' perceptions and practices with regards to discussing health policy issues with families and to identify provider characteristics associated with having these discussions. METHODS: In this cross-sectional mixed methods study, pediatric resident physicians, attending physcians, and nurse practitioners at primary care clinics within a large academic health system were surveyed to assess (1) perceived importance of, (2) frequency of, and (3) barriers to and facilitators of health policy discussions with families. Multivariable ordinal regression was used to determine provider characteristics (including demographics, practice location, and extent of civic engagement) associated with frequency of these discussions. A subset of providers participated in subsequent focus groups designed to help interpret quantitative findings. RESULTS: The overall survey response rate was 155/394 (39%). The majority of respondents (76%) felt pediatricians should talk to families about health policy issues affecting children, but most providers (69%) reported never or rarely having these discussions. Factors associated with discussing policy issues included being an attending physician/nurse practitioner (OR 8.22, 95% CI 2.04-33.1) and urban practice setting (OR 3.85, 95% CI 1.03-14.3). Barriers included feeling uninformed about relevant issues and time constraints. In provider focus groups, four key themes emerged: (1) providers felt discussing policy issues would help inform and empower families; (2) providers frequently discussed social service programs, but rarely discussed policies governing these programs; (3) time constraints and concerns about partisan bias were a barrier to conversations; and (4) use of support staff and handouts with information about policy changes could help facilitate more frequent conversations. CONCLUSIONS: Pediatric providers felt it was important to talk to families about child health policy issues, but few providers reported having such conversations in practice. Primary care practices should consider incorporating workflow changes that promote family engagement in relevant health policy discussions.

Knockin mouse model of the human CFL2 p.A35T mutation results in a unique splicing defect and severe myopathy phenotype.

Cofilin-2 is an actin-binding protein that is predominantly expressed in skeletal and cardiac muscles and belongs to the AC group of proteins, which includes cofilin-1 and destrin. In humans, cofilin-2 (CFL2) mutations have been associated with congenital myopathies that include nemaline and myofibrillar myopathy. To understand the pathogenicity of the human CFL2 mutation, p.A35T, that first linked cofilin-2 with the human disease, we created a knock-in mouse model. The Cfl2A35T/A35T (KI) mice were indistinguishable from their wild-type littermates at birth, but they rapidly worsened and died by postnatal day 9. The phenotypic, histopathologic and molecular findings mimicked the constitutive Cfl2-knockout (KO) mice described previously, including sarcomeric disruption and actin accumulations in skeletal muscles and negligible amounts of cofilin-2 protein. In addition, KI mice demonstrated a marked reduction in Cfl2 mRNA levels in various tissues including skeletal muscles. Further investigation revealed evidence of alternative splicing with the presence of two alternate transcripts of smaller size. These alternate transcripts were expressed at very low levels in the wild-type mice and were significantly upregulated in the mutant mice, indicating that pre-translational splicing defects may be a critical component of the disease mechanism associated with the mutation. Evidence of reduced expression of the full-length CFL2 transcript was also observed in the muscle biopsy sample of the patient with p.A35T mutation.

Perceived Access to Outpatient Care and Hospital Reutilization Following Acute Respiratory Illnesses.

OBJECTIVE: Efforts to decrease hospital revisits often focus on improving access to outpatient follow-up. Our objective was to assess the relationship between perceived access to timely office-based care and subsequent 30-day revisits following hospital discharge for 4 common respiratory illnesses. METHODS: This was a prospective cohort study of children 2 weeks to 16years admitted to 5 US children's hospitals for asthma, bronchiolitis, croup, or pneumonia between July 2014 and June 2016. Hospital and emergency department (ED) (in the case of croup) admission surveys administered to caregivers included the Consumer Assessments of Healthcare Providers and Systems Timely Access to Care. Access composite scores (range 0-100, with greater scores indicating better access) were linked with 30-day ED revisits and inpatient readmissions from the Pediatric Health Information System. The relationship between access to timely care and repeat utilization was assessed using multivariable logistic regression adjusting for demographics, hospitalization, and home/outpatient factors. RESULTS: Of the 2438 children enrolled, 2179 (89%) reported an office visit in the previous 6 months. Average access composite score was 52.0 (standard deviation, 36.3). In adjusted analyses, greater access scores were associated with greater odds of 30-day ED revisits (odds ratio [OR] = 1.07; 95% confidence interval [CI], 1.02-1.13)-particularly for croup (OR = 1.17; 95% CI, 1.02-1.36)-but not inpatient readmissions (OR = 1.02; 95% CI, 0.96-1.09). CONCLUSIONS: Perceived access to timely office-based care was associated with significantly greater odds of subsequent ED revisit. Focusing solely on enhancing timely access to care following discharge for common respiratory illnesses may be insufficient to prevent repeat utilization.

Concerns and Expectations of Parents Seeking Subspecialist Care for Their Child's Short Stature.

INTRODUCTION: Parents (PP) of children in primary care clinics previously reported factors influencing their height-related medical decision making. However, patients seeking height-related care in endocrine subspecialty clinics and their parents (EP) differ demographically from the general population. OBJECTIVE: To determine EP height-related medical concerns and expectations, and to compare between EP and PP. METHODS: EP completed a survey assessing their concerns in seeking medical care for their child's height with identical questions previously asked of PP and two additional questions about growth hormone (GH) treatment. RESULTS: A greater proportion of the 166 EP (80% response rate) than the 1,820 PP (83% response rate) previously surveyed was Caucasian (75% EP, 41% PP) and privately insured (80% EP, 58% PP). Both groups rated treatment efficacy and risks most as having a bigor extreme impact on decision making (65% EP, 58% PP). The second most rated concern for EP was comparison of child's height to peers or growth chart (60% EP, 32% PP) versus child's health for PP (54% EP, 56% PP). Of the 166 EP surveyed, 76% rated GH treatment as potentially improving quality of life (QoL), with 88% reporting a minimum 3-inch height increase as necessary to improve QoL. CONCLUSIONS: Height comparisons were more likely to impact EP than PP in seeking height-related medical care for their children. EP had high expectations of QoL improvement with GH treatment, which are unlikely to be met with treatment of idiopathic short stature. Thus, clinicians should be prepared to support families in other ways that promote positive development in children with short stature.