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BACKGROUND: In the United States, rare disease (RD) is defined as a condition that affects fewer than 200,000 individuals. Collectively, RD affects an estimated 30 million Americans. A significant portion of RD has an underlying genetic cause; however, this may go undiagnosed. To better serve these patients, the Mayo Clinic Program for Rare and Undiagnosed Diseases (PRaUD) was created under the auspices of the Center for Individualized Medicine (CIM) aiming to integrate genomics into subspecialty practice including targeted genetic testing, research, and education. METHODS: Patients were identified by subspecialty healthcare providers from 11 clinical divisions/departments. Targeted multi-gene panels or custom exome/genome-based panels were utilized. To support the goals of PRaUD, a new clinical service model, the Genetic Testing and Counseling (GTAC) unit, was established to improve access and increase efficiency for genetic test facilitation. The GTAC unit includes genetic counselors, genetic counseling assistants, genetic nurses, and a medical geneticist. Patients receive abbreviated point-of-care genetic counseling and testing through a partnership with subspecialty providers. RESULTS: Implementation of PRaUD began in 2018 and GTAC unit launched in 2020 to support program expansion. Currently, 29 RD clinical indications are included in 11 specialty divisions/departments with over 142 referring providers. To date, 1152 patients have been evaluated with an overall solved or likely solved rate of 17.5% and as high as 66.7% depending on the phenotype. Noteworthy, 42.7% of the solved or likely solved patients underwent changes in medical management and outcome based on genetic test results. CONCLUSION: Implementation of PRaUD and GTAC have enabled subspecialty practices advance expertise in RD where genetic counselors have not historically been embedded in practice. Democratizing access to genetic testing and counseling can broaden the reach of patients with RD and increase the diagnostic yield of such indications leading to better medical management as well as expanding research opportunities.
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Enfermedades Raras , Enfermedades no Diagnosticadas , Estados Unidos , Humanos , Enfermedades Raras/diagnóstico , Enfermedades Raras/genética , Enfermedades Raras/terapia , Atención Terciaria de Salud , Medicina Genómica , Pruebas Genéticas , Asesoramiento GenéticoRESUMEN
OBJECTIVES: To evaluate the frequency and severity of new cases of youth-onset type 2 diabetes in the US during the first year of the pandemic compared with the mean of the previous 2 years. STUDY DESIGN: Multicenter (n = 24 centers), hospital-based, retrospective chart review. Youth aged ≤21 years with newly diagnosed type 2 diabetes between March 2018 and February 2021, body mass index ≥85th percentile, and negative pancreatic autoantibodies were included. Demographic and clinical data, including case numbers and frequency of metabolic decompensation, were compared between groups. RESULTS: A total of 3113 youth (mean [SD] 14.4 [2.4] years, 50.5% female, 40.4% Hispanic, 32.7% Black, 14.5% non-Hispanic White) were assessed. New cases of type 2 diabetes increased by 77.2% in the year during the pandemic (n = 1463) compared with the mean of the previous 2 years, 2019 (n = 886) and 2018 (n = 765). The likelihood of presenting with metabolic decompensation and severe diabetic ketoacidosis also increased significantly during the pandemic. CONCLUSIONS: The burden of newly diagnosed youth-onset type 2 diabetes increased significantly during the coronavirus disease 2019 pandemic, resulting in enormous strain on pediatric diabetes health care providers, patients, and families. Whether the increase was caused by coronavirus disease 2019 infection, or just associated with environmental changes and stressors during the pandemic is unclear. Further studies are needed to determine whether this rise is limited to the US and whether it will persist over time.
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COVID-19 , Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Cetoacidosis Diabética , Niño , Adolescente , Humanos , Femenino , Masculino , Pandemias , COVID-19/epidemiología , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , Estudios Retrospectivos , Cetoacidosis Diabética/complicacionesRESUMEN
BACKGROUND: We sought to evaluate the association between vitamin D deficiency and the severity of coronavirus disease 2019 (COVID-19) infection. METHODS: Multiple databases from 1 January 2019 to 3 December 2020 were searched for observational studies evaluating the association between vitamin D deficiency and severity of COVID-19 infection. Independent reviewers selected studies and extracted data for the review. The main outcomes of interest were mortality, hospital admission, length of hospital stay and intensive care unit admission. RESULTS: Seventeen observational studies with 2756 patients were included in the analyses. Vitamin D deficiency was associated with significantly higher mortality (odds ratio [OR]: 2.47, 95% confidence interval [CI]: 1.50-4.05; 12 studies; hazard ratio [HR]: 4.11, 95% CI: 2.40-7.04; 3 studies), higher rates of hospital admissions (OR: 2.18, 95% CI: 1.48-3.21; 3 studies) and longer hospital stays (0.52 days; 95% CI: 0.25-0.80; 2 studies) as compared to nonvitamin D deficient status. Subgroup analyses based on different cut-offs for defining vitamin D deficiency, study geographic locations and latitude also showed similar trends. CONCLUSIONS: Vitamin D deficiency is associated with greater severity of COVID-19 infection. Further studies are warranted to determine if vitamin D supplementation can decrease the severity of COVID-19.
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COVID-19 , Deficiencia de Vitamina D , Humanos , Unidades de Cuidados Intensivos , SARS-CoV-2 , Vitamina D , Deficiencia de Vitamina D/complicacionesRESUMEN
PURPOSE OF REVIEW: Cardiovascular disease is the leading cause of death in patients with type 1 diabetes (T1D) and type 2 diabetes (T2D). Subclinical atherosclerotic changes are noted in youth with diabetes; therefore, timely identification and management of modifiable cardiovascular risk factors including hyperlipidemia is crucial. We review the current guidelines for hyperlipidemia screening and treatment in youth with T1D and T2D. We discuss the efficacy of non-pharmacological strategies including dietary modifications, exercise, and glycemic control and pharmacological therapy. We summarize reported rates of treatment of diabetes-related hyperlipidemia in youth. RECENT FINDINGS: Hyperlipidemia is prevalent among youth with T1D and T2D. Vast majority of youth with diabetes-related hyperlipidemia do not receive lipid-lowering treatments. There are several factors that contribute to suboptimal management of hyperlipidemia in youth with diabetes including limited data on efficacy and safety of statins in youth with diabetes. We propose strategies to improve hyperlipidemia management including education of providers and patients, quality improvement methods, and electronic health record alerts. Additionally, further studies are warranted to examine the safety of statins in youth with diabetes, cost-benefit analysis to aggressive screening and treatment, and long-term effect for improving cardiovascular morbidity and mortality.
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Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Hiperlipidemias , Adolescente , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Humanos , Hiperlipidemias/terapia , Factores de RiesgoRESUMEN
Spexin (SPX) is a 14-amino acid neuropeptide, discovered recently using bioinformatic techniques. It is encoded by the Ch12:orf39 gene that is widely expressed in different body tissues/organs across species, and secreted into systemic circulation. Recent reports have highlighted a potentially important regulatory role of SPX in obesity and related comorbidities. SPX is also ubiquitously expressed in human tissues, including white adipose tissue. The circulating concentration of SPX is significantly lower in individuals with obesity compared to normal weight counterparts. SPX's role in obesity appears to be related to various factors, such as the regulation of energy expenditure, appetite, and eating behaviors, increasing locomotion, and inhibiting long-chain fatty acid uptake into adipocytes. Recent reports have also suggested SPX's relationship with novel biomarkers of cardiovascular disease (CVD) and glucose metabolism and evoked the potential role of SPX as a key biomarker/player in the early loss of cardiometabolic health and development of CVD and diabetes later in life. Data on age-related changes in SPX and SPX's response to various interventions are also emerging. The current review focuses on the role of SPX in obesity and related comorbidities across the life span, and its response to interventions in these conditions. It is expected that this article will provide new ideas for future research on SPX and its metabolic regulation, particularly related to cardiometabolic diseases.
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Síndrome Metabólico/genética , Obesidad/genética , Hormonas Peptídicas/farmacología , Biomarcadores/análisis , Biomarcadores/sangre , Conducta Alimentaria/efectos de los fármacos , Humanos , Síndrome Metabólico/sangre , Obesidad/sangre , Hormonas Peptídicas/análisis , Hormonas Peptídicas/metabolismoRESUMEN
OBJECTIVE: To determine the trends in testing and incidence of vitamin D deficiency/insufficiency in Olmsted County, Minnesota over a 16-year period. STUDY DESIGN: The Rochester Epidemiology Project (REP) was used to identify Olmsted County, Minnesota residents aged <19 years who had 25-hydroxyvitamin D [25(OH)D] levels measured between January 2, 2002 and December 31, 2017. Using each patient's first 25(OH)D measurement during this period, patients were categorized into 3 groups: <20 ng/mL, 20-50 ng/mL, and >50 ng/mL. Vitamin D deficiency/insufficiency was defined as a total 25(OH)D level of <20 ng/mL. RESULTS: There was a 42-fold increase in the proportion of the county's pediatric population tested each year, starting at 3.7 per 10 000 persons in 2002 and increasing to 156.1 per 10 000 persons in 2017. The largest increase in testing occurred in children aged ≥10 years, specifically the females in this age group, in whom we observed a 90-fold increase from 2002 to 2017. During the 16-year period, the incidence of vitamin D deficiency/insufficiency (per 10 000 persons) increased from 1.7 in 2002-2003 to 19.9 in 2016-2017, but the proportion that were tested and had vitamin D deficiency/insufficiency remained stable, with rates of 21.9% (95% CI, 16.1%-29.1%) in 2006-2007 and 18.5% (95% CI, 16.0%-21.2%) in 2016-2017. CONCLUSIONS: The proportion of the county's pediatric population who underwent vitamin D testing increased from 2002 to 2017, in parallel to the increased incidence of vitamin D deficiency/insufficiency, but the proportion tested that had vitamin D deficiency/insufficiency remained stable over time.
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Pautas de la Práctica en Medicina/tendencias , Deficiencia de Vitamina D/diagnóstico , Deficiencia de Vitamina D/epidemiología , Adolescente , Biomarcadores/sangre , Niño , Preescolar , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Minnesota/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Vitamina D/análogos & derivados , Vitamina D/sangre , Deficiencia de Vitamina D/sangre , Deficiencia de Vitamina D/etiologíaRESUMEN
BACKGROUND: Adolescents and emerging adults with chronic health conditions such as type 1 diabetes mellitus (T1D) are more likely to engage in high-risk behaviors. Previous studies regarding substance use in adolescents and emerging adults with T1D are mostly derived from cross-sectional studies utilizing self-administered questionnaires and are limited by lack of population-based comparison groups. In addition, despite the rising popularity of vaping, little is known about the incidence of vaping in adolescents and emerging adults with T1D. METHODS: We explored the incidence and prospective risk of substance use disorders (SUD) and vaping in adolescents and emerging adults with T1D compared to age and gender matched nondiabetic referents residing in Olmsted County, Rochester, MN. RESULTS: Risk of incident SUD was higher in those with T1D compared to matched referents with alcohol, marijuana, and smoked tobacco being most common substances. When stratified by gender, these differences remained significant in males, but not females. CONCLUSIONS: While further work is needed to delineate the causative relationships between T1D, mental health, and substance abuse, our findings confirm the critical need for substance use screening and mental health support for adolescents and emerging adults with T1D.
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Complicaciones de la Diabetes/epidemiología , Diabetes Mellitus Tipo 1/psicología , Trastornos Relacionados con Sustancias/epidemiología , Vapeo/epidemiología , Adolescente , Adulto , Niño , Estudios de Cohortes , Femenino , Humanos , Masculino , Minnesota/epidemiología , Adulto JovenRESUMEN
OBJECTIVES: To examine main factors that influence the decision to choose pediatric endocrinology as a career among pediatric endocrinologists and assess their work satisfaction or stress level and suggested strategies to increase interest in subspecialty training in pediatric endocrinology. METHODS: A workforce survey was distributed among 1470 members of the Pediatric Endocrine Society. RESULTS: The response rate was 37.4%, with 550 members responding. The most common reasons for the respondents choosing pediatric endocrinology were intellectual stimulation (79%), exposure to endocrinology during residency (57%) or medical school (43%), and ability to establish relationships with patients with chronic disorders (54%). Of the respondents, 97% considered intellectual stimulation as the most favorable aspect of the specialty, and 84% considered financial compensation as the most unfavorable aspect of pediatric endocrinology. Majority (77%) were satisfied or very satisfied with their work environment. The mean work-related stress score (0 [none] to 10 [worst]) was 5.7, standard deviation was 2.1, and median was 6 (Q1, Q3: 4, 7). Increased financial compensation for the services and loan payment or forgiveness option were the top strategies suggested to enhance interest among residents for training in the subspecialty. One third (37%) felt that reducing the duration of the fellowship to 2 years would increase interest in training in pediatric endocrinology. CONCLUSION: The pediatric endocrinologists reported overall excellent career satisfaction, indicating the potential to attract high-quality doctors to the specialty. Improving reimbursement and loan forgiveness were the top strategies suggested for increasing interest in subspecialty training in pediatric endocrinology.
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Endocrinología , Internado y Residencia , Selección de Profesión , Niño , Endocrinólogos , Endocrinología/educación , Becas , Humanos , Encuestas y CuestionariosRESUMEN
OBJECTIVE: To describe treatment outcomes of children and adolescents enrolled in the Pediatric Obesity Weight Evaluation Registry, a consortium of multicomponent pediatric weight management programs in the US. STUDY DESIGN: This multicenter prospective observational cohort study, established in 2013, includes youth (2-18 years of age) with obesity enrolled from 31 Pediatric Obesity Weight Evaluation Registry (POWER) sites over a 2-year period and followed up to 12 months. Weight status was evaluated by the percentage of the 95th percentile for body mass index (%BMIp95). Associations of weight status outcomes with patient characteristics and program exposure were analyzed with multivariable mixed effects modeling. RESULTS: We included 6454 children and adolescents (median age, 11 years; IQR, 9-14 years; 53% white, 32% Hispanic; 73% with severe obesity) who were enrolled in POWER. Median changes in %BMIp95 for this cohort were -1.88 (IQR, -5.8 to 1.4), -2.50 (IQR, -7.4 to 1.8), -2.86 (IQR, -8.7 to 1.9), at 4-6, 7-9, and 10-12 of months follow-up, respectively (all P < .05). Older age (≥12 years), greater severity of obesity, and Hispanic race/ethnicity were associated with better improvement in %BMIp95. A 5-percentage point decrease in %BMIp95 was associated with improvement in cardiometabolic risk factors. CONCLUSIONS: Overall, treatment in pediatric weight management programs is associated with a modest median decrease in BMI as measured by change in %BMIp95. Further studies are needed to confirm these findings, as well as to identify additional strategies to enhance the effectiveness of these multicomponent interventions for youth with severe obesity. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02121132.
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Obesidad Infantil/terapia , Programas de Reducción de Peso , Adolescente , Presión Sanguínea , Índice de Masa Corporal , Niño , Estudios de Cohortes , Femenino , Estado de Salud , Humanos , Masculino , Factores de Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND: There is a lack of consensus on the cardiometabolic consequences of mild subclinical hypothyroidism (SCH) among children. The objective of the current study was to compare lipid profiles in children with mild SCH with those of euthyroid children. STUDY DESIGN: Retrospective medical record review. PATIENTS: Children (ages 2-18 years) who had undergone simultaneous measurement of TSH, free thyroxine (T4) and lipids. Lipids in children with mild SCH (TSH 5-<10 mIU/L and normal free T4, n = 228) were compared with those in euthyroid children (n = 1215). RESULTS: TSH level was positively associated with total cholesterol and nonhigh density lipoprotein (non-HDL) cholesterol [ß 0.05(0.03-0.08), P < .0001 and ß 0.05(0.03-0.08), P < .0001, respectively]. Total cholesterol was significantly higher in children and adolescents with mild SCH compared with euthyroid children (4.43 ± 1.14 mmol/L vs 4.2 ± 0.85 mmol/L, P = .0005). Similarly, non-HDL cholesterol level was also higher in children with mild SCH relative to euthyroid children (3.08 ± 1.14 mmol/L vs 2.91 ± 0.8 mmol/L, P = .001). The adjusted odds ratio of having elevated total cholesterol and elevated non-HDL cholesterol was greater in children with mild SCH compared with euthyroid children (OR 1.88, 95% CI; 1.28-2.73; P = .001 and 1.72, 95% CI 1.2-2.5; P = .003, respectively). The presence of thyroid autoimmunity was not associated with higher rates of dyslipidaemia. CONCLUSIONS: Mild SCH in children and adolescents was associated with higher rates of elevated total cholesterol and elevated non-HDL cholesterol. Randomized placebo controlled studies are warranted to determine if treatment of mild SCH in children leads to improvement in lipid profile.
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Dislipidemias/sangre , Dislipidemias/complicaciones , Hipotiroidismo/sangre , Hipotiroidismo/etiología , Adolescente , Niño , Colesterol/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Femenino , Humanos , Masculino , Estudios Retrospectivos , Pruebas de Función de la Tiroides , Tirotropina/sangreRESUMEN
Adverse family experiences (AFEs) are associated with childhood obesity. We evaluated whether certain positive contextual factors reduce the risk of obesity and overweight among children exposed to AFEs in a nationally representative sample. Using data derived from the National Survey of Children's Health 2011-12 (Nâ¯=â¯43,864), we calculated the distribution of positive contextual factors (very good/excellent maternal mental health, neighborhood and school safety, and child resilience) and AFEs across weight status. The AFEs composite score was modeled as a categorical measure (0 or ≥1 AFEs). Positive contextual factors, AFEs and their interactions were evaluated in weighted, adjusted, multinomial logistic regression models predicting the odds of overweight and obesity. Children exposed to lack of very good/excellent maternal mental health and at least one AFE were at risk for overweight (ORâ¯=â¯1.43; 95% CI: 1.16, 1.76) and obesity (ORâ¯=â¯1.53; 95% CI: 1.22, 1.93). Unsafe school or neighborhood environment and exposure to 1 or more AFEs was. associated with overweight (ORâ¯=â¯1.32; 95% CI: 1.08, 1.61) and obesity (ORâ¯=â¯1.66; 95% CI: 1.34, 2.05). Lack of child resilience and exposure to 1 or more AFEs was associated with an increased risk of obesity (ORâ¯=â¯1.45; 95% CI: 1.17, 1.90) and overweight (ORâ¯=â¯1.29; 95% CI: 1.06, 1.57). These odds of obesity and overweight all decreased when positive contextual factors were present. Among children exposed to AFEs, overweight and obesity risk is reduced with positive contextual factors. Optimizing the early childhood environment can impact obesity risk.
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Experiencias Adversas de la Infancia/estadística & datos numéricos , Familia/psicología , Obesidad Infantil , Características de la Residencia , Adolescente , Factores de Edad , Niño , Estudios Transversales , Femenino , Encuestas Epidemiológicas , Humanos , Masculino , Obesidad Infantil/etnología , Resiliencia Psicológica , Factores de Riesgo , Factores Sexuales , Factores SocioeconómicosRESUMEN
BACKGROUND: Children with active inflammatory bowel disease (IBD) are frequently underweight. Anti-tumor necrosis factor (anti-TNF) agents may induce remission and restore growth. However, its use in other autoimmune diseases has been associated with excess weight gain. Our aim was to examine whether children with IBD could experience excess weight gain. METHODS: A centralized diagnostic index identified pediatric IBD patients evaluated at our institution who received anti-TNF therapy for at least 1 year between August 1998 and December 2013. Anthropometric data were collected at time of anti-TNF initiation and annually. Excess weight gain was defined as ΔBMI SDS (standard deviation score) where patients were (1) reclassified from "normal" to "overweight/obese," (2) "overweight" to "obese," or (2) a final BMI SDS >0 and ΔSDS >0.5. RESULTS: During the study period, 268 children received anti-TNF therapy. Of these, 69 had sufficient follow-up for a median of 29.3 months. Median age at first anti-TNF dose was 12.8 years. At baseline, mean weight SDS was -0.7 (SD 1.4), while mean BMI SDS was -0.6 (1.3). Using baseline BMI SDS, 11.6% were overweight/obese. At last follow-up (LFU), however, the mean ΔBMI SDS was 0.50 (p < 0.0001). However, 10 (17%) patients had excess weight gain at LFU; 3 patients were reclassified from "normal" to "obese," and 7 had a final BMI SDS >0 and ΔSDS >0.5. CONCLUSIONS: Pediatric patients with IBD may experience excess weight gain when treated with anti-TNF agents. Monitoring for this side effect is warranted.
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Productos Biológicos/efectos adversos , Colitis Ulcerosa/tratamiento farmacológico , Enfermedad de Crohn/tratamiento farmacológico , Fármacos Gastrointestinales/efectos adversos , Obesidad Infantil/inducido químicamente , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Aumento de Peso/efectos de los fármacos , Adolescente , Edad de Inicio , Niño , Preescolar , Colitis Ulcerosa/diagnóstico , Colitis Ulcerosa/inmunología , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/inmunología , Femenino , Humanos , Masculino , Obesidad Infantil/diagnóstico , Obesidad Infantil/fisiopatología , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
BACKGROUND: Vitamin D insufficiency has been associated with immune dysfunction and linked to the epidemic of atopic diseases in the Western hemisphere, yet there are studies with conflicting results, and the risk has not been quantified uniformly across studies. OBJECTIVE: To perform a systematic review and meta-analysis to evaluate and quantify if vitamin D deficiency is associated with the presence and persistence of food allergy. METHODS: A systematic review was undertaken to assess for the association between food allergy and vitamin D status in children. RESULTS: A total of 368 citations relevant to this systematic review were identified. In the whole review, 5105 children were included. We did not find a significant association between 25 hydroxy vitamin D (25(OH)D) status and risk of food allergy in children (odds ratio [OR] 1.35 [95% confidence interval {CI}, 0.79-2.29]; p = 0.27, I2 = 58.3%). We conducted subgroup analyses based on different cutoffs of the 25(OH)D status (20 versus 30 ng/mL). Only one study used 30 ng/mL and found that children with <30 ng/mL were more likely to report food allergy than children with a 25(OH)D status of ≥30 ng/mL (OR 2.04 [95% CI, 1.02-4.04]; p = 0.04). Four studies compared children with a 25(OH)D status of <20 ng/mL to children with a 25(OH)D status of ≥20 ng/mL and found no significant differences (OR 1.18 [95% CI, 0.62-2.27]; p = 0.62, I2 = 62.7%). CONCLUSION: Based on the studies analyzed, this systematic review did not identify a significant association between vitamin D status and food allergy. Interpretation of the included studies was limited by a lack of a standard definition for vitamin D deficiency and insufficient knowledge regarding the optimal vitamin D status needed to impact immune function. Longitudinal studies are warranted to assess if vitamin D might contribute to the development of food allergy.
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Hipersensibilidad a los Alimentos/etiología , Deficiencia de Vitamina D/complicaciones , Vitamina D/normas , Niño , Humanos , Oportunidad Relativa , Vitamina D/inmunologíaRESUMEN
While exposure to adverse family experiences (AFEs), subset of adverse childhood experiences (ACEs), has been associated with childhood obesity, less is known about the impact of exposures to each type of AFE. Using 2011-2012 National Survey of Children's Health data, we evaluated associations between exposure to individual AFEs and overweight/obesity status in children 10years or older, adjusting for socio-demographic factors. Caregivers reported their child's height, weight, and exposure to nine AFEs; body mass index (BMI) was classified by Center for Disease Control and Prevention's (CDC) guidelines. At Mayo Clinic, we calculated frequencies and weighted estimates of socio-demographic factors and AFEs. Unadjusted and adjusted weighted multinomial logistic regression models were employed to assess the independent associations of each AFE and the different AFE composite scores with BMI category. Exposure to two or more AFEs was independently associated with increased odds of overweight (odds ratio [OR], 1.33; 95% confidence interval [CI], 1.13, 1.56) and obese (OR, 1.45; 95% CI, 1.21, 1.73) status after adjustment for age, household income, parents' education-level, race and sex. Death of parent (OR, 1.59; 95% CI, 1.18, 2.15) and hardship due to family income (OR, 1.26; 95% CI, 1.06, 1.50) were independently associated with obesity status with adjustment for other AFEs and socio-demographic factors. Our results suggest that, in addition to cumulative exposure to AFEs, exposure to certain childhood experiences are more strongly associated with childhood obesity than others. Death of parent and hardship due to family income are individual AFEs, which are strongly predictive of obesity.
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Maltrato a los Niños/psicología , Conflicto Familiar/psicología , Relaciones Padres-Hijo , Obesidad Infantil/epidemiología , Adolescente , Índice de Masa Corporal , Niño , Femenino , Humanos , Renta/estadística & datos numéricos , Masculino , Encuestas y Cuestionarios , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: There is increasing interest in the extraskeletal effects of vitamin D, particularly in the obese state with regard to the development of insulin resistance and diabetes. OBJECTIVE: The objective of the study was to determine the effect of 2 doses of cholecalciferol (vitamin D3) supplementation on insulin action (Si) and pancreatic ß-cell function in obese adolescents. METHODS: We performed a 12-wk double-blind, randomized comparison of the effect of vitamin D3 supplementation on Si and ß-cell function in obese Caucasian adolescents (body mass index > 95(th) percentile). The subjects were randomly assigned to receive either 400 IU/d (n = 25) or 2000 IU/d (n = 26) of vitamin D3. Each subject underwent a 7-sample 75 g oral glucose tolerance test, with glucose, insulin, and C-peptide measurements, to calculate Si and ß-cell function as assessed by the disposition index (DI), with use of the oral minimal model before and after supplementation. A total of 51 subjects aged 15.0 ± 1.9 y were enrolled. Included for analysis at follow-up were a total of 46 subjects (20 male and 26 female adolescents), 23 in each group. RESULTS: Initial serum 25-hydroxyvitamin D [25(OH)D] was 24.0 ± 8.1 µg/L. There was no correlation between 25(OH)D concentrations and Si or DI. There was a modest but significant increase in 25(OH)D concentration in the 2000 IU/d group (3.1 ± 6.5 µg/L, P = 0.04) but not in the 400 IU/d group (P = 0.39). There was no change in Si or DI following vitamin D3 supplementation in either of the treatment groups (all P > 0.10). CONCLUSIONS: The current study shows no effect from vitamin D3 supplementation, irrespective of its dose, on ß-cell function or insulin action in obese nondiabetic adolescents with relatively good vitamin D status. Whether obese adolescents with vitamin D deficiency and impaired glucose metabolism would respond differently to vitamin D3 supplementation remains unclear and warrants further studies. This trial was registered at clinicaltrials.gov as NCT00858247.
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Colecalciferol/administración & dosificación , Suplementos Dietéticos , Células Secretoras de Insulina/efectos de los fármacos , Insulina/sangre , Obesidad/sangre , Adolescente , Glucemia/metabolismo , Índice de Masa Corporal , Niño , Colecalciferol/sangre , Método Doble Ciego , Femenino , Estudios de Seguimiento , Voluntarios Sanos , Humanos , Resistencia a la Insulina , Células Secretoras de Insulina/metabolismo , Masculino , Estudios Prospectivos , Resultado del Tratamiento , Vitaminas/administración & dosificaciónRESUMEN
Aim: To demonstrate the importance of critical reagent characterization for immunogenicity assay development for multi-specific drugs using two case studies. Methods: Bridging anti-drug antibody (ADA) assay with acid-dissociated samples were used for both cases. Results: In the first case study, the unexpected interference in an ADA assay from clinical samples was identified; a model was created to replicate the issue, and an anti-target antibody was identified to mitigate the target interference. In the second case study, an issue due to non-specific binding of a domain-specific confirmatory reagent was identified, and various mitigation techniques were evaluated. Conclusion: A thorough characterization of the critical reagents helped identify the issues with these ADA case studies and provided strategies for resolving them.
[Box: see text].
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Background: Early childhood weight trajectory is associated with future risk for obesity. However, little is known about the association of birth weight and weight trajectories before age 5.5 years with severe adult obesity. Methods: This study used a nested case-control design of 785 matched sets of cases and controls matched 1:1 on age and gender from a 1976 to 1982 birth cohort in Olmsted County, Minnesota. Cases with severe adult obesity were defined as individuals with a BMI ≥40 kg/m2 after 18 years of age. There were 737 matched sets of cases and controls for the trajectory analysis. Weight and height data from birth through 5.5 years were abstracted from the medical records, and weight-for-age percentiles were obtained from the CDC growth charts. Results: A two-cluster weight-for-age trajectory solution was identified as optimal, with cluster 1 having higher weight-for-age before age 5.5 years. While there was no association between birth weight and severe adult obesity, the odds of being in cluster 1, which includes children with higher weight-for-age percentiles, was significantly increased for cases compared with controls [odds ratio (OR) 1.99, 95% confidence interval (CI) 1.60-2.47]. The association between cluster membership and case-control status persisted after adjusting for maternal age and education (adjusted OR 2.08, 95% CI 1.66-2.61). Conclusions: Our data suggest that early childhood weight-for-age trajectories are associated with severe obesity status in adult life. Our results add to growing evidence that it is critical to prevent excess early childhood weight gain.
Asunto(s)
Trayectoria del Peso Corporal , Obesidad Mórbida , Obesidad Infantil , Niño , Adulto , Preescolar , Humanos , Obesidad Mórbida/complicaciones , Obesidad Mórbida/epidemiología , Peso al Nacer , Estudios de Casos y Controles , Obesidad Infantil/epidemiología , Factores de Riesgo , Índice de Masa Corporal , Aumento de PesoRESUMEN
Context: Variants in melanocortin 4 receptor (MC4R) pathway-related genes have been associated with obesity. The association of these variants with cardiometabolic parameters are not fully known. Objective: We compared the severity of obesity and cardiometabolic risk markers in children with MC4R pathway-related clinically reported genetic variants relative to children without these variants. Methods: A retrospective chart review was performed in children with obesity who underwent multigene panel testing for monogenic obesity. Results: Data on a total of 104 children were examined, with 93 (89%) identified as White. Thirty-nine (37.5%) patients had clinically reported variants in the MC4R pathway, and the remaining 65 patients did not have reported MC4R pathway-related variants. Among the MC4R-related variants, PCSK1 risk alleles were most common, reported in 15 children (14%). The maximum body mass index percent of the 95th percentile was not different between groups (P = .116). Low-density lipoprotein cholesterol (LDL-C) was not different between groups (P = .132). However, subgroup analysis demonstrated higher LDL cholesterol in children with the PCSK1 c.661A>G risk allele relative to those with MC4R-related variant of uncertain significance (P = .047), negative genetic testing (P = .012), and those with non-MC4R related variants (P = .048). The blood pressure, fasting glucose, hemoglobin A1C, total cholesterol, alanine transaminase, and high-density lipoprotein cholesterol were not different between groups. Conclusion: Variants in the MC4R pathway-related genes were not associated with severity of obesity and cardiometabolic risk markers except for the c.661A>G PCSK1 risk allele, which was associated with higher LDL-C levels.