RESUMO
MOTIVATION: statistics from genome-wide association studies enable many valuable downstream analyses that are more efficient than individual-level data analysis while also reducing privacy concerns. As growing sample sizes enable better-powered analysis of gene-environment interactions, there is a need for gene-environment interaction-specific methods that manipulate and use summary statistics. RESULTS: We introduce two tools to facilitate such analysis, with a focus on statistical models containing multiple gene-exposure and/or gene-covariate interaction terms. REGEM (RE-analysis of GEM summary statistics) uses summary statistics from a single, multi-exposure genome-wide interaction study to derive analogous sets of summary statistics with arbitrary sets of exposures and interaction covariate adjustments. METAGEM (META-analysis of GEM summary statistics) extends current fixed-effects meta-analysis models to incorporate multiple exposures from multiple studies. We demonstrate the value and efficiency of these tools by exploring alternative methods of accounting for ancestry-related population stratification in genome-wide interaction study in the UK Biobank as well as by conducting a multi-exposure genome-wide interaction study meta-analysis in cohorts from the diabetes-focused ProDiGY consortium. These programs help to maximize the value of summary statistics from diverse and complex gene-environment interaction studies. AVAILABILITY AND IMPLEMENTATION: REGEM and METAGEM are open-source projects freely available at https://github.com/large-scale-gxe-methods/REGEM and https://github.com/large-scale-gxe-methods/METAGEM.
Assuntos
Interação Gene-Ambiente , Estudo de Associação Genômica Ampla , Modelos Estatísticos , Tamanho da Amostra , Interpretação Estatística de Dados , Polimorfismo de Nucleotídeo Único , FenótipoRESUMO
PURPOSE OF REVIEW: The purpose of this review is to describe the existing limited data related to the use of semaglutide in adolescents with obesity, supplementing with findings from adult studies of semaglutide use. RECENT FINDINGS: Semaglutide, as a once weekly subcutaneous injection for weight management, effectively reduces body mass index (BMI) while improving hyperglycemia, elevated alanine aminotransferase levels, hyperlipidemia, and quality of life in youth with obesity. As of this review, only one large randomized clinical trial of semaglutide in youth has been completed, with a follow-up duration of 68âweeks. Thus, long-term data on the safety in adolescents is limited, particularly regarding the risks of cholelithiasis, pancreatitis, suicidal ideation, and disordered eating. Due to the cost of semaglutide, particularly in the United States, limited cost effectiveness analyses have demonstrated unfavorable incremental cost-effectiveness ratios for semaglutide relative to phentermine-topiramate as an alternative antiobesity medication in adolescents. SUMMARY: Semaglutide represents an important advance in the pediatric obesity management, with clear short-term reductions in BMI and improvement in metabolic parameters. However, its long-term safety and efficacy for youth with obesity remain to be demonstrated. Additional research is needed to assess trends in utilization and adherence to minimize the risk of worsening socioeconomic disparities in pediatric obesity.
Assuntos
Fármacos Antiobesidade , Peptídeos Semelhantes ao Glucagon , Obesidade Infantil , Humanos , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Peptídeos Semelhantes ao Glucagon/efeitos adversos , Adolescente , Obesidade Infantil/tratamento farmacológico , Fármacos Antiobesidade/uso terapêutico , Fármacos Antiobesidade/efeitos adversos , Resultado do Tratamento , Índice de Massa Corporal , Análise Custo-Benefício , Injeções Subcutâneas , Redução de Peso/efeitos dos fármacos , Qualidade de VidaRESUMO
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.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Adolescente , Idade de Início , Criança , Quimioterapia Combinada , Feminino , Humanos , Masculino , Estudos RetrospectivosRESUMO
BACKGROUND: Prediabetes awareness in adults has been associated with improved weight management. Whether youth with prediabetes diagnosis experience similar improvements is unknown. OBJECTIVE: To investigate the association between prediabetes identification and body mass index (BMI) trajectory in overweight and obese adolescents. SUBJECTS: Youth who were followed longitudinally in a large academic-affiliated primary care network and who were overweight/obese while 10 to 18 years old. METHODS: Retrospective cohort study. Subjects were categorized as "screened" if at least 1 hemoglobin A1c (HbA1c) result was available. Time series analysis was used to determine the difference in difference (DID) in BMI Z-score (BMI-Z) slope before and after HbA1c between: (a) screened youth found to have prediabetes-range HbA1c (5.7%-6.4%, 39-46 mmol/mol) versus normal HbA1c and (b) screened versus age-matched unscreened obese youth. RESULTS: A total of 4184 (55.6% female) screened subjects (median follow-up 9.7 years) were included. In which, 637 (15.2%) had prediabetes-range HbA1c. Prediabetes was associated with a greater decrease in BMI-Z slope than normal HbA1c (DID: -0.023/year [95% CI: -0.042 to -0.004]). When compared to age-matched unscreened subjects (n = 2087), screened subjects (n = 2815) experienced a greater decrease in BMI-Z slope after HbA1c than unscreened subjects at a matched age (DID: -0.031/y [95% CI -0.042 to -0.021]). CONCLUSIONS: BMI-Z trajectory improved more among youth with prediabetes-range HbA1c but also stabilized in screened youth overall. Prospective studies are needed to identify provider- and patient-level drivers of this observation.
Assuntos
Trajetória do Peso do Corpo , Sobrepeso/epidemiologia , Obesidade Infantil/epidemiologia , Estado Pré-Diabético/epidemiologia , Adolescente , Índice de Massa Corporal , Criança , Estudos de Coortes , Feminino , Humanos , Masculino , Estado Pré-Diabético/diagnóstico , Estudos Retrospectivos , Estados Unidos/epidemiologiaRESUMO
BACKGROUND & AIMS: Celiac disease can reduce bone mineral density. We sought to determine the prevalence and risk factors for low areal bone mineral density (aBMD) in children with celiac disease. METHODS: We performed a retrospective cohort study of 673 children with celiac disease (63% female; median age at diagnosis, 10.6 y; interquartile range, 7.8-13.9) who underwent dual x-ray absorptiometry (DXA) from 2009 through 2016 at the Children's Hospital of Philadelphia. We collected demographic, clinical, and laboratory data from medical records. We performed logistic regression analysis to identify factors associated with low (Z less than -2) lumbar spine aBMD Z (aBMD-Z) scores at initial and subsequent tests. RESULTS: The time between diagnosis of celiac disease and first DXA was 0 days (interquartile range, -11 to 31 d). The mean aBMD-Z score at the children's initial scan was -0.4 ± 1.2; 46 children had aBMD-Z scores less than -2 (6.8%; 95% CI, 5.2%-9.0%). Those who had a second DXA analysis (n = 108; 16.0%) had a significant increase in aBMD-Z score (mean change, 0.29; P = .0005). Higher body mass index (BMI) was associated with lower odds of a low aBMD-Z score at the initial DXA analysis (odds ratio, 0.46, 95% CI, 0.35-0.50). BMI-Z scores greater than -0.4 identified children with a low aBMD-Z at their initial DXA analysis with a 95% negative predictive value. CONCLUSIONS: Approximately 7% of subjects with celiac disease had a low aBMD-Z score, determined by DXA, at the time of diagnosis; this value was nearly 3-fold higher than expected from a population of children of this age and sex distribution. BMI-Z scores could be used to identify children with celiac disease at risk for low BMD who should receive DXA screening.
Assuntos
Densidade Óssea/fisiologia , Doenças Ósseas Metabólicas/etiologia , Doença Celíaca/epidemiologia , Vértebras Lombares/diagnóstico por imagem , Absorciometria de Fóton , Adolescente , Doenças Ósseas Metabólicas/diagnóstico , Doenças Ósseas Metabólicas/epidemiologia , Doença Celíaca/complicações , Doença Celíaca/diagnóstico , Criança , Feminino , Seguimentos , Humanos , Masculino , Pennsylvania/epidemiologia , Prevalência , Prognóstico , Estudos RetrospectivosRESUMO
PURPOSE OF REVIEW: Because the incidence of type 2 diabetes and prediabetes in children is rising, routine screening of those at risk is recommended. In 2010, the ADA made the recommendation to include hemoglobin A1c (HbA1c) as a diagnostic test for diabetes, in addition to the oral glucose tolerance test or fasting plasma glucose. Our objective was to assess the pediatric literature with regard to HbA1c test performance and discuss advantages and disadvantages of use of the test for diagnostic purposes. RECENT FINDINGS: HbA1c has a number of advantages, including elimination of the need for fasting, lower variability, assay standardization, and long-term association with future development of diabetes. It also has many drawbacks. It can be affected by a number of non-glycemic factors, including red blood cell turnover, hemoglobinopathies, medications, race, and age. In particular, it performs differently in children compared with adults, generally with lower sensitivity for prediabetes (as low as 0-5% in children vs 23-27% in adults) and lower area under the receiver operating characteristic curve (AUC) (0.53 vs 0.73 for prediabetes), and it has lower efficacy at a higher cost, compared with other tests of glycemia. Finally, HbA1c may perform very differently across diverse populations according to race/ethnicity; in Chinese populations, the proportion of individuals classified with prediabetes based on HbA1c predominates compared with IFG (77% for HbA1c vs 27.7% for IFG), whereas in US populations, it is the opposite (24.8% for HbA1c vs 80.1% for FPG). HbA1c is controversial because although it is convenient, it is not a true measure of glycemia. The interpretation of HbA1c results requires a nuanced understanding that many primary care physicians who are ordering the test in greater numbers do not possess. Alternative markers of glycemia may hold promise for the future but are not yet endorsed for use in practice. Further studies are needed to determine appropriate thresholds for screening tests and the long-term impact of screening and identification.
Assuntos
Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Hemoglobinas Glicadas/análise , Estado Pré-Diabético/sangue , Estado Pré-Diabético/diagnóstico , Glicemia/análise , Diabetes Mellitus Tipo 2/economia , Diabetes Mellitus Tipo 2/epidemiologia , Humanos , Médicos de Atenção Primária , Estado Pré-Diabético/economia , Estado Pré-Diabético/epidemiologia , Fatores de RiscoRESUMO
PURPOSE OF REVIEW: Congenital hyperinsulinism is the most common cause of persistent hypoglycemia in infants and children. Early and appropriate recognition and treatment of hypoglycemia is vital to minimize neurocognitive impairment. RECENT FINDINGS: There are at least 11 known monogenic forms of hyperinsulinism and several associated syndromes. Molecular diagnosis allows for prediction of the effectiveness of diazoxide and the likelihood of focal hyperinsulinism. Inactivating mutations in the genes encoding the ATP-sensitive potassium channel (KATP hyperinsulinism) account for 60% of all identifiable mutations, including 85% of diazoxide-unresponsive cases. Syndromes or disorders associated with hyperinsulinism include Beckwith-Wiedemann syndrome, Kabuki syndrome, Turner syndrome, and congenital disorders of glycosylation. Although focal hyperinsulinism can be cured by resection of the lesion, therapeutic options for nonfocal hyperinsulinism remain limited and include diazoxide, octreotide, long-acting somatostatin analogs, and near-total pancreatectomy. Although sirolimus has been reported to improve glycemic control in infants with diazoxide-unresponsive hyperinsulinism, the extent of improvement has been limited, and significant adverse events have been reported. SUMMARY: Identification of the cause of congenital hyperinsulinism helps guide management decisions. Use of therapies with limited benefit and significant potential risks should be avoided.
Assuntos
Hiperinsulinismo Congênito/genética , Criança , Hiperinsulinismo Congênito/complicações , Hiperinsulinismo Congênito/diagnóstico , Hiperinsulinismo Congênito/terapia , Marcadores Genéticos , Testes Genéticos , Humanos , Lactente , SíndromeRESUMO
OBJECTIVE: To determine the incidence of and risk factors for development of celiac disease (CD) in individuals with type 1 diabetes. METHODS: Cohort study using The Health Improvement Network (THIN), a UK primary care database of >13 million people. Individuals with incident type 1 diabetes diagnosed at 1 to 35 years of age between 1995 and 2015 with no previous diagnosis of CD were included. Cox regression was used to identify risk factors for CD, including age at diabetes diagnosis and sex, while adjusting for year of diagnosis to control for potential rising incidence in CD over time. RESULTS: Subjects (n = 9180; 43% female) had a median observation time of 5.1 years (interquartile range 2.0-10.1). CD was diagnosed in 196 (2%) during follow up. Median time to diagnosis was 2.1 years, but 25% were diagnosed more than 5 years after diabetes diagnosis. Incidence (per 10 000 person-years) was greater in females (43.0 [95% confidence interval [CI] 35.2-52.0]) vs males (26.8 [95% CI 21.5-32.9]). In multivariable Cox regression stratified by childhood- vs young adult-onset diabetes, younger age at diabetes diagnosis within childhood (hazard ratio [HR] 0.91 [95% CI 0.88-0.94]) and female sex among the adult-onset diabetes group (HR 3.19 [95% CI 1.39-7.34]) were associated with greater risk of CD. CONCLUSIONS: As expected, incidence of CD was higher in individuals with childhood-onset diabetes vs those with adult-onset diabetes. However, individuals with diabetes are at risk of developing CD throughout childhood and adulthood, and prolonged screening after diagnosis may be warranted. Prospective studies are needed in order to guide risk-stratified approaches to screening.
Assuntos
Doença Celíaca/epidemiologia , Doença Celíaca/etiologia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/epidemiologia , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Redes Comunitárias/organização & administração , Redes Comunitárias/estatística & dados numéricos , Bases de Dados Factuais/estatística & dados numéricos , Feminino , Promoção da Saúde/métodos , Promoção da Saúde/organização & administração , Humanos , Incidência , Lactente , Masculino , Atenção Primária à Saúde/organização & administração , Atenção Primária à Saúde/estatística & dados numéricos , Fatores de Risco , Reino Unido/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Paediatric obesity disproportionately impacts individuals from minoritized racial and ethnic backgrounds. Recent guidelines support use of anti-obesity pharmacotherapy for adolescents with obesity, but the potential impact on disparities in obesity prevalence has not been evaluated. OBJECTIVES: To model changes in obesity prevalence with increasing utilization of anti-obesity pharmacotherapy among adolescents. METHODS: Data representative of American adolescents ages 12-17 years were obtained from the National Health and Nutrition Examination Survey, cycles 2011 through pre-pandemic 2020. A body mass index (BMI) reduction of 16.7% was applied to each participant based on clinical trial results of weekly subcutaneous semaglutide 2.4 mg among adolescents. Utilization disparities were based on utilization of the same medication class among adults. Obesity prevalence was calculated assuming utilization of 10%-100%, stratified by race and ethnicity. RESULTS: Among 4442 adolescents representing 26 247 384 American adolescents, projected overall obesity prevalence decreased from 22.2% to 8.4% with 100% utilization. However, disparities increased relative to Non-Hispanic White youth, with prevalence among Non-Hispanic Black and Mexican American youth ranging from 40%-60% higher to 90%-120% higher, respectively. CONCLUSIONS: Increasing utilization of anti-obesity pharmacotherapy may widen relative disparities in obesity, particularly if utilization is unequal. Advocacy for equitable access is needed to minimize worsening of obesity-related disparities.
Assuntos
Etnicidade , Disparidades nos Níveis de Saúde , Obesidade Infantil , Adolescente , Criança , Humanos , Índice de Massa Corporal , Inquéritos Nutricionais , Obesidade Infantil/tratamento farmacológico , Obesidade Infantil/etnologia , Estados Unidos/epidemiologia , Redução de Peso , Ensaios Clínicos como AssuntoRESUMO
INTRODUCTION: Among youth with type 1 diabetes (T1D), longitudinal poor glycemic control is associated with adverse socioeconomic conditions at the neighborhood level. Child Opportunity Index (COI), which encompasses measures of education, health, environment, social, and economic factors, is associated with obesity in youth but has not been evaluated in youth with new-onset T1D or type 2 diabetes (T2D). We hypothesized that lower COI would be associated with adverse clinical outcomes at diabetes diagnosis, and due to differing risk factors and pathophysiology, that youth with new-onset T2D would have lower COI than youth with T1D. RESEARCH DESIGN AND METHODS: Retrospective cohort of youth with new-onset diabetes admitted to a large academic pediatric hospital. COI was compared by diabetes type using t-tests and Χ2 tests. Multivariable linear and logistic regression analyses were used to evaluate associations between COI and clinical characteristics, stratified by diabetes type and adjusted for age and sex. RESULTS: The cohort (n=484) differed in race and age by diabetes type (T1D: n=389; 10.0% black, 81.2% white; age 9.6±0.2 years; T2D: n=95; 44.2% black, 48.4% white; age 14.8±0.3 years). Youth with T2D had lower COI (p<0.001). Low COI was associated with diabetic ketoacidosis in T1D and T2D. Black youth with low COI had the highest hemoglobin A1c among youth with T2D and the highest obesity prevalence among youth with T1D. CONCLUSIONS: COI is associated with differing characteristics at diagnosis in youth-onset T1D and T2D but is worse among youth with T2D overall. These findings underscore the need to address socioeconomic adversity when designing interventions to reduce T2D risk and to improve outcomes at diabetes diagnosis in youth.
Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Criança , Humanos , Adolescente , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Obesidade/complicaçõesRESUMO
BACKGROUND: Recent pediatric guidelines recommend clinicians offer anti-obesity medication (AOM) as an adjunct to intensive lifestyle intervention. OBJECTIVE: To investigate pediatricians' perspectives about prescribing AOM, including barriers and facilitators. METHODS: An investigator-developed survey was emailed to primary care pediatric physicians (n = 187) and advanced practice providers (n = 190) within an academic-affiliated network. The survey evaluated how willing clinicians were to prescribe AOM and their agreement with 25 statements about barriers and facilitators. Three vignettes explored AOM decision-making. Multinomial logistic regression was used to determine relative risk ratios for willingness to prescribe by agreement with each statement. RESULTS: Among 74 respondents (20% response rate), 24% were willing, 42% uncertain and 34% unwilling to prescribe. Most (64%) agreed that AOM should be managed only by specialists. Willingness to prescribe was associated with clinician motivation and belief in guideline practicality and applicability. Unwillingness was associated with beliefs that patients would not continue AOM long enough for benefit and that there was insufficient time or resources to implement. In vignettes, 52% were willing to prescribe AOM for a patient with severe obesity and metabolic complications, versus 11% for a patient with obesity and possible disordered eating. CONCLUSIONS: Willingness to prescribe AOM was low and was associated with perceived practicality and appropriateness for patients.
Assuntos
Fármacos Antiobesidade , Atitude do Pessoal de Saúde , Obesidade Infantil , Padrões de Prática Médica , Atenção Primária à Saúde , Humanos , Obesidade Infantil/tratamento farmacológico , Fármacos Antiobesidade/uso terapêutico , Feminino , Masculino , Adolescente , Padrões de Prática Médica/estatística & dados numéricos , Adulto , Pediatras/psicologia , Pediatras/estatística & dados numéricos , Inquéritos e Questionários , Pessoa de Meia-IdadeRESUMO
Importance: Several clinical practice guidelines advise race- and ethnicity-based screening for youth-onset type 2 diabetes (T2D) due to a higher prevalence among American Indian and Alaska Native, Asian, Black, and Hispanic youths compared with White youths. However, rather than a biological risk, this disparity likely reflects the inequitable distribution of adverse social determinants of health (SDOH), a product of interpersonal and structural racism. Objective: To evaluate prediabetes prevalence by presence or absence of adverse SDOH in adolescents eligible for T2D screening based on weight status. Design, Setting, and Participants: This cross-sectional study and analysis used data from the 2011 to 2018 cycles of the National Health and Nutrition Examination Survey. Data were analyzed from June 1, 2023, to April 5, 2024. Participants included youths aged 12 to 18 years with body mass index (BMI) at or above the 85th percentile without known diabetes. Main Outcomes and Measures: The main outcome consisted of an elevated hemoglobin A1c (HbA1c) level greater than or equal to 5.7% (prediabetes or undiagnosed presumed T2D). Independent variables included race, ethnicity, and adverse SDOH (food insecurity, nonprivate health insurance, and household income <130% of federal poverty level). Survey-weighted logistic regression was used to adjust for confounders of age, sex, and BMI z score and to determine adjusted marginal prediabetes prevalence by race, ethnicity, and adverse SDOH. Results: The sample included 1563 individuals representing 10â¯178â¯400 US youths aged 12 to 18 years (mean age, 15.5 [95% CI, 15.3-15.6] years; 50.5% [95% CI, 47.1%-53.9%] female; Asian, 3.0% [95% CI, 2.2%-3.9%]; Black, 14.9% [95% CI, 11.6%-19.1%]; Mexican American, 18.8% [95% CI, 15.4%-22.9%]; Other Hispanic, 8.1% [95% CI, 6.5%-10.1%]; White, 49.1% [95% CI, 43.2%-55.0%]; and >1 or other race, 6.1% [95% CI, 4.6%-8.0%]). Food insecurity (4.1% [95% CI, 0.7%-7.5%]), public insurance (5.3% [95% CI, 1.6%-9.1%]), and low income (5.7% [95% CI, 3.0%-8.3%]) were each independently associated with higher prediabetes prevalence after adjustment for race, ethnicity, and BMI z score. While Asian, Black, and Hispanic youths had higher prediabetes prevalence overall, increasing number of adverse SDOH was associated with higher prevalence among White youths (8.3% [95% CI, 4.9%-11.8%] for 3 vs 0.6% [95% CI, -0.7% to 2.0%] for 0 adverse SDOH). Conclusions and Relevance: Adverse SDOH were associated with higher prediabetes prevalence, across and within racial and ethnic categories. Consideration of adverse SDOH may offer a more actionable alternative to race- and ethnicity-based screening to evaluate T2D risk in youth.
Assuntos
Diabetes Mellitus Tipo 2 , Estado Pré-Diabético , Determinantes Sociais da Saúde , Adolescente , Criança , Feminino , Humanos , Masculino , Índice de Massa Corporal , Estudos Transversais , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/etnologia , Etnicidade/estatística & dados numéricos , Insegurança Alimentar , Hemoglobinas Glicadas/análise , Inquéritos Nutricionais , Estado Pré-Diabético/epidemiologia , Estado Pré-Diabético/etnologia , Prevalência , Determinantes Sociais da Saúde/estatística & dados numéricos , Estados Unidos/epidemiologia , Indígena Americano ou Nativo do Alasca , Asiático , Negro ou Afro-Americano , Hispânico ou Latino , BrancosRESUMO
Common dysglycemia measurements including fasting plasma glucose (FPG), oral glucose tolerance test (OGTT)-derived 2 h plasma glucose, and hemoglobin A1c (HbA1c) have limitations for children. Dynamic OGTT glucose and insulin responses may better reflect underlying physiology. This analysis assessed glucose and insulin curve shapes utilizing classifications-biphasic, monophasic, or monotonically increasing-and functional principal components (FPCs) to predict future dysglycemia. The prospective cohort included 671 participants with no previous diabetes diagnosis (BMI percentile ≥ 85th, 8-18 years old); 193 returned for follow-up (median 14.5 months). Blood was collected every 30 min during the 2 h OGTT. Functional data analysis was performed on curves summarizing glucose and insulin responses. FPCs described variation in curve height (FPC1), time of peak (FPC2), and oscillation (FPC3). At baseline, both glucose and insulin FPC1 were significantly correlated with BMI percentile (Spearman correlation r = 0.22 and 0.48), triglycerides (r = 0.30 and 0.39), and HbA1c (r = 0.25 and 0.17). In longitudinal logistic regression analyses, glucose and insulin FPCs predicted future dysglycemia (AUC = 0.80) better than shape classifications (AUC = 0.69), HbA1c (AUC = 0.72), or FPG (AUC = 0.50). Further research should evaluate the utility of FPCs to predict metabolic diseases.
RESUMO
PURPOSE: Youth-onset type 2 diabetes (T2D) is increasingly common and is often diagnosed shortly before transition from pediatric to adult care. Little is known about the experience of emerging adults (EAs) with T2D and the readiness, barriers, and facilitators to transition. This study sought to describe the illness experience of EAs with T2D and perceptions about transition, and explore themes by "transition readiness," measured by the Transition Readiness Assessment Questionnaire (TRAQ). METHODS: In this mixed-methods study, we conducted semi-structured interviews with EAs with T2D using a guide grounded in the health belief model, administered the TRAQ, and collected disease metrics from the electronic medical record. We developed a coding scheme using a directed content-analysis approach and triangulated qualitative and quantitative data to compare themes stratified by mean TRAQ score. RESULTS: Participants described modifying factors like adjusting to life with a chronic illness and coping with mental health issues as critical elements of the illness experience that influence transition. Individual beliefs emerged including the perceived risk of disease complications being informed by experience of family members, self-efficacy in diabetes care hinging on the ability to be highly organized, and transition as a daunting obstacle with numerous emotional and logistical barriers. Participants emphasized the need for support from caregivers and providers throughout transition. Themes did not vary significantly by TRAQ score. DISCUSSION: Experiences of EAs with T2D suggest more assistance is needed in the transition period to address factors such as mental health, organizational skills, and identifying support people to facilitate care.
Assuntos
Diabetes Mellitus Tipo 2 , Transição para Assistência do Adulto , Humanos , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 2/psicologia , Masculino , Feminino , Adulto Jovem , Adolescente , Adaptação Psicológica , Adulto , Inquéritos e Questionários , Entrevistas como Assunto , Pesquisa QualitativaRESUMO
AIMS: To evaluate relationships of hypoglycemia awareness, hypoglycemia beliefs, and continuous glucose monitoring (CGM) glycemic profiles with anxiety and depression symptoms in adults with type 1 diabetes (T1D) who use CGM. METHODS: A cross-sectional survey and data collections were completed with 196 T1D adults who used CGM (59% also used automated insulin delivery devices (AIDs)). We assessed hypoglycemia awareness (Gold instrument), hypoglycemia beliefs (Attitudes to Awareness of Hypoglycemia instrument), CGM glycemic profiles, demographics, and anxiety and depression symptoms (Hospital Anxiety and Depression Scale). Analysis included simple and multiple linear regression analyses. RESULTS: Lower hypoglycemia awareness, weaker "hypoglycemia concerns minimized" beliefs, stronger "hyperglycemia avoidance prioritized" beliefs were independently associated with higher anxiety symptoms (P < 0.05), with similar trends in both subgroups using and not using AIDs. Lower hypoglycemia awareness were independently associated with greater depression symptoms (P < 0.05). In participants not using AIDs, more time in hypoglycemia was related to less anxiety and depression symptoms (P < 0.05). Being female and younger were independently associated with higher anxiety symptoms, while being younger was also independently associated with greater depression symptoms (P < 0.05). CONCLUSION: Our findings revealed relationships of impaired hypoglycemia awareness, hypoglycemia beliefs, CGM-detected hypoglycemia with anxiety and depression symptoms in T1D adults who use CGMs.
Assuntos
Diabetes Mellitus Tipo 1 , Hipoglicemia , Adulto , Humanos , Feminino , Masculino , Diabetes Mellitus Tipo 1/complicações , Glicemia , Automonitorização da Glicemia , Monitoramento Contínuo da Glicose , Estudos Transversais , Depressão/diagnóstico , Depressão/epidemiologia , Depressão/etiologia , Hipoglicemia/etiologia , Hipoglicemia/complicações , Ansiedade/diagnóstico , Ansiedade/epidemiologia , Ansiedade/etiologia , Hipoglicemiantes/efeitos adversos , Insulina/efeitos adversosRESUMO
Context: Steatotic liver disease is common but overlooked in childhood obesity; diagnostic methods are invasive or expensive. Objective: We sought to determine the diagnostic accuracy of vibration-controlled transient elastography (VCTE) compared with magnetic resonance imaging (MRI) in adolescents with obesity and high risk for hepatosteatosis. Methods: Baseline data in 3 clinical trials enrolling adolescents with obesity were included (NCT03919929, NCT03717935, NCT04342390). Liver fat was assessed using MRI fat fraction and VCTE-based controlled attenuation parameter (CAP). Hepatosteatosis was defined as MRI fat fraction ≥5.0%. The area under the receiver-operating characteristic curves (AUROCs) for CAP against MRI was calculated, and optimal CAP using the Youden index for hepatosteatosis diagnosis was determined. Results: Data from 82 adolescents (age 15.6 ± 1.4 years, body mass index 36.5 ± 5.9 kg/m2, 81% female) were included. Fifty youth had hepatosteatosis by MRI (fat fraction 9.3% ; 95% CI 6.7, 14.0), and 32 participants did not have hepatosteatosis (fat fraction 3.1%; 95% CI 2.2, 3.9; P < .001). The hepatosteatosis group had higher mean CAP compared with no hepatosteatosis (293 dB/m; 95% CI 267, 325 vs 267 dB/m; 95% CI 248, 282; P = .0120). A CAP of 281 dB/m had the highest sensitivity (60%) and specificity (74%) with AUROC of 0.649 (95% CI 0.51-0.79; P = .04) in the entire cohort. In a subset of participants with polycystic ovary syndrome (PCOS), a CAP of 306 dB/m had the highest sensitivity (78%) and specificity (52%) and AUROC of 0.678 (95% CI 0.45-0.90; P = .108). Conclusion: CAP of 281 dB/m has modest diagnostic performance for hepatosteatosis compared with MRI in youth with significant obesity. A higher CAP in youth with PCOS suggests that comorbidities might affect optimal CAP in hepatosteatosis diagnosis.
RESUMO
Obesity affects approximately 1 in 5 youth globally and increases the risk of complications during adolescence and young adulthood, including type 2 diabetes, dyslipidemia, hypertension, non-alcoholic fatty liver disease, obstructive sleep apnea, and polycystic ovary syndrome. Children and adolescents with obesity frequently experience weight stigma and have an impaired quality of life, which may exacerbate weight gain. Pediatric obesity is typically defined using sex-, age-, and population-specific body mass index percentiles. Once identified, pediatric obesity should always be managed with lifestyle modification. However, adolescents with obesity may also benefit from anti-obesity medications (AOM), several of which have been approved for use in adolescents by the US Food and Drug Administration, including liraglutide, phentermine/topiramate, and semaglutide. For children with specific, rare monogenic obesity disorders, setmelanotide is available and may lead to significant weight loss. Metabolic and bariatric surgery may be used for the management of severe obesity in youth; though highly effective, it is limited to specialized centers and has had relatively low pediatric uptake. In this narrative review using pediatric-focused data from original research, reviews, clinical practice guidelines, governmental agencies, and pharmaceutical companies, we review obesity-related metabolic complications in youth and management strategies, including AOM and bariatric surgery.
RESUMO
OBJECTIVE: To use combined glycemic (HbA1c) and BMI z-score (BMIZ) trajectories spanning the coronavirus disease 2019 (COVID-19) pandemic to identify high-risk subgroups of adolescents with diabetes. RESEARCH DESIGN AND METHODS: Retrospective cohort of adolescents 10-19 years old with type 1 and type 2 diabetes with one or more visits at a large pediatric hospital from January 2018 through February 2020 (prepandemic) and April 2020 through August 2021 (pandemic). Group-based trajectory models were used to identify latent classes of combined BMIZ and HbA1c trajectories. Multinomial logistic regression was used to evaluate predictors of class membership, including Area Deprivation Index (ADI) (socioeconomic status proxy). RESULTS: The cohort included 1,322 youth with type 1 diabetes (93% White and 7% Black) and 59 with type 2 diabetes (53% Black and 47% White). For type 1 diabetes, six trajectory classes emerged. Black youth were more likely to be in the class with worsening glycemic control and concurrent BMIZ decrease at pandemic onset (relative risk ratio [RRR] vs. White: 3.0 [95% CI 1.3-6.8]) or in the class with progressively worsening glycemic control and obesity (RRR 3.0 [95% CI 1.3-6.8]), while those from the most deprived neighborhoods (RRR ADI tertile 3 vs. 1: 1.9 [95% CI 1.2-2.9]) were more likely to be in the class with stable obesity and glycemic control. For type 2 diabetes, three distinct trajectories emerged, two of which experienced worsening glycemic control with concurrent BMIZ decline at pandemic onset. CONCLUSIONS: Race and neighborhood deprivation were independently associated with distinct glycemic and BMIZ trajectory classes in youth with diabetes, highlighting persistent and widening disparities associated with the COVID-19 pandemic.
Assuntos
COVID-19 , Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Criança , Humanos , Adolescente , Adulto Jovem , Adulto , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/complicações , Estudos Retrospectivos , Pandemias , Hemoglobinas Glicadas , Índice de Massa Corporal , Controle Glicêmico , COVID-19/complicações , Obesidade/complicaçõesRESUMO
Importance: Lifestyle change is central to diabetes risk reduction in youth with overweight or obesity. Feeling susceptible to a health threat can be motivational in adults. Objective: To evaluate associations between diabetes risk perception and/or awareness and health behaviors in youth. Design, Setting, and Participants: This cross-sectional study analyzed data from the US National Health and Nutrition Examination Survey 2011 to 2018. Participants included youths aged 12 to 17 years with body mass index (BMI) in the 85th percentile or higher without known diabetes. Analyses were conducted from February 2022 to February 2023. Main Outcomes and Measures: Outcomes included physical activity, screen time, and attempted weight loss. Confounders included age, sex, race and ethnicity, and objective diabetes risk (BMI, hemoglobin A1c [HbA1c]). Exposures: Independent variables included diabetes risk perception (feeling at risk) and awareness (told by clinician), as well as potential barriers (eg, food insecurity, household size, insurance). Results: The sample included 1341 individuals representing 8â¯716â¯794 US youths aged 12 to 17 years with BMI in the 85th percentile or higher for age and sex. The mean age was 15.0 years (95% CI, 14.9-15.2 years) and mean BMI z score was 1.76 (95% CI 1.73-1.79). Elevated HbA1c was present in 8.6% (HbA1c 5.7%-6.4%: 8.3% [95% CI, 6.5%-10.5%]; HbA1c ≥6.5%: 0.3% [95% CI, 0.1%-0.7%]). Nearly one-third of youth with elevated HbA1c reported risk perception (30.1% [95% CI, 23.1%-38.1%), while one-quarter (26.5% [95% CI, 20.0%-34.2%]) had risk awareness. Risk perception was associated with increased TV watching (ß = 0.3 hours per day [95% CI, 0.2-0.5 hours per day]) and approximately 1 less day per week with at least 60 minutes of physical activity (ß = -1.2 [95% CI, -2.0 to -0.4) but not with nutrition or weight loss attempts. Awareness was not associated with health behaviors. Potential barriers had mixed associations: larger households (≥5 members vs 1-2) reported lower consumption of non-home-prepared meals (OR 0.4 [95% CI, 0.2-0.7]) and lower screen time (ß = -1.1 hours per day [95% CI, -2.0 to -0.3 hours per day), while public insurance (vs private) was associated with approximately 20 fewer minutes per day of physical activity (ß = -20.7 minutes per day [95% CI, 35.5 to -5.8 minutes per day]). Conclusions and Relevance: In this cross-sectional study including a US-representative sample of adolescents with overweight or obesity, diabetes risk perception and awareness were not associated with greater engagement in risk-reducing behaviors in youth. These findings suggest the need to address barriers to engagement in lifestyle change, including economic disadvantage.
Assuntos
Diabetes Mellitus , Sobrepeso , Adulto , Humanos , Adolescente , Hemoglobinas Glicadas , Estudos Transversais , Inquéritos Nutricionais , Obesidade , Redução de Peso , PercepçãoRESUMO
PURPOSE: The purpose of this study was to identify factors impacting the acceptability of continuous glucose monitoring (CGM) in adolescents and young adults (AYAs) with type 2 diabetes mellitus (T2DM). METHODS: In this single-center study, semistructured interviews were conducted with AYAs with T2DM and their parents to determine attitudes about CGM, including barriers and facilitators. Interviews were audio-recorded, transcribed, and evaluated using thematic analysis. RESULTS: Twenty AYAs and 10 parents participated (n = 30 total). AYAs were mean age 16.5 years (SD 2.2, range = 13.7-20.1) and had median diabetes duration of 1.3 years. Most were female (65%) and from minoritized background (40% non-Hispanic Black, 10% Hispanic, 5% Asian). Seven (35%) used CGM. The primary facilitator elicited was convenience over glucose meter use. Important barriers included the impact of physically wearing the device and drawing unwanted attention, desire for AYA privacy, and inadequate education about the device. CONCLUSIONS: In this diverse sample of AYAs with T2DM and their parents, CGM was generally regarded as convenient, although concerns about worsening stigma and conflict with parents were prevalent. These findings can guide the development of patient-centered approaches to CGM for AYAs with T2DM, a critical step toward reducing inequities in diabetes technology uptake.