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1.
Diabetologia ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38910151

RESUMO

Given the proven benefits of screening to reduce diabetic ketoacidosis (DKA) likelihood at the time of stage 3 type 1 diabetes diagnosis, and emerging availability of therapy to delay disease progression, type 1 diabetes screening programmes are being increasingly emphasised. Once broadly implemented, screening initiatives will identify significant numbers of islet autoantibody-positive (IAb+) children and adults who are at risk of (confirmed single IAb+) or living with (multiple IAb+) early-stage (stage 1 and stage 2) type 1 diabetes. These individuals will need monitoring for disease progression; much of this care will happen in non-specialised settings. To inform this monitoring, JDRF in conjunction with international experts and societies developed consensus guidance. Broad advice from this guidance includes the following: (1) partnerships should be fostered between endocrinologists and primary-care providers to care for people who are IAb+; (2) when people who are IAb+ are initially identified there is a need for confirmation using a second sample; (3) single IAb+ individuals are at lower risk of progression than multiple IAb+ individuals; (4) individuals with early-stage type 1 diabetes should have periodic medical monitoring, including regular assessments of glucose levels, regular education about symptoms of diabetes and DKA, and psychosocial support; (5) interested people with stage 2 type 1 diabetes should be offered trial participation or approved therapies; and (6) all health professionals involved in monitoring and care of individuals with type 1 diabetes have a responsibility to provide education. The guidance also emphasises significant unmet needs for further research on early-stage type 1 diabetes to increase the rigour of future recommendations and inform clinical care.

2.
J Gen Intern Med ; 39(8): 1488-1491, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38499724

RESUMO

COVID-19 vaccination is estimated to have averted more than 2.4 million deaths globally. In the United States (U.S.) alone, more than 120,000 deaths and 700,000 hospitalizations are reportedly estimated to have been prevented during the first six months of the vaccine campaign. Despite the overwhelming evidence regarding the safety and efficacy of vaccination, COVID-19 vaccine hesitancy continues to pose a significant threat to public health. Notably, an unexpected source of vaccine misinformation has been the Surgeon General of the State of Florida, Dr. Joseph Ladapo. While both a tenured faculty member of the University of Florida, College of Medicine and the Surgeon General of Florida, Dr. Ladapo has delivered official Florida Department of Health statements regarding COVID-19 vaccines that run contrary to those of the U.S. Centers for Disease Control and Prevention (CDC). While tenure is designed to protect those with contrarian views, we believe that the University has an ethical obligation to condemn misleading statements that put public health at risk. Herein, we explore the challenges of managing misinformation disseminated by someone who is simultaneously a tenured professor at a public, state-supported university, and a politically appointed public health official.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Comunicação , Humanos , Vacinas contra COVID-19/efeitos adversos , Florida/epidemiologia , COVID-19/prevenção & controle , COVID-19/epidemiologia , Hesitação Vacinal/psicologia , Saúde Pública , Comunicação em Saúde/métodos
3.
PLoS Comput Biol ; 19(2): e1010914, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36848379

RESUMO

Environmentally induced or epigenetic-related beta-cell dysfunction and insulin resistance play a critical role in the progression to diabetes. We developed a mathematical modeling framework capable of studying the progression to diabetes incorporating various diabetogenic factors. Considering the heightened risk of beta-cell defects induced by obesity, we focused on the obesity-diabetes model to further investigate the influence of obesity on beta-cell function and glucose regulation. The model characterizes individualized glucose and insulin dynamics over the span of a lifetime. We then fit the model to the longitudinal data of the Pima Indian population, which captures both the fluctuations and long-term trends of glucose levels. As predicted, controlling or eradicating the obesity-related factor can alleviate, postpone, or even reverse diabetes. Furthermore, our results reveal that distinct abnormalities of beta-cell function and levels of insulin resistance among individuals contribute to different risks of diabetes. This study may encourage precise interventions to prevent diabetes and facilitate individualized patient treatment.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Humanos , Diabetes Mellitus Tipo 2/complicações , Resistência à Insulina/fisiologia , Insulina , Obesidade/complicações , Glucose , Glicemia
4.
N Engl J Med ; 383(21): 2007-2017, 2020 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-33207093

RESUMO

BACKGROUND: Type 1 diabetes is an autoimmune disease characterized by progressive loss of pancreatic beta cells. Golimumab is a human monoclonal antibody specific for tumor necrosis factor α that has already been approved for the treatment of several autoimmune conditions in adults and children. Whether golimumab could preserve beta-cell function in youth with newly diagnosed overt (stage 3) type 1 diabetes is unknown. METHODS: In this phase 2, multicenter, placebo-controlled, double-blind, parallel-group trial, we randomly assigned, in a 2:1 ratio, children and young adults (age range, 6 to 21 years) with newly diagnosed overt type 1 diabetes to receive subcutaneous golimumab or placebo for 52 weeks. The primary end point was endogenous insulin production, as assessed according to the area under the concentration-time curve for C-peptide level in response to a 4-hour mixed-meal tolerance test (4-hour C-peptide AUC) at week 52. Secondary and additional end points included insulin use, the glycated hemoglobin level, the number of hypoglycemic events, the ratio of fasting proinsulin to C-peptide over time, and response profile. RESULTS: A total of 84 participants underwent randomization - 56 were assigned to the golimumab group and 28 to the placebo group. The mean (±SD) 4-hour C-peptide AUC at week 52 differed significantly between the golimumab group and the placebo group (0.64±0.42 pmol per milliliter vs. 0.43±0.39 pmol per milliliter, P<0.001). A treat-to-target approach led to good glycemic control in both groups, and there was no significant difference between the groups in glycated hemoglobin level. Insulin use was lower with golimumab than with placebo. A partial-remission response (defined as an insulin dose-adjusted glycated hemoglobin level score [calculated as the glycated hemoglobin level plus 4 times the insulin dose] of ≤9) was observed in 43% of participants in the golimumab group and in 7% of those in the placebo group (difference, 36 percentage points; 95% CI, 22 to 55). The mean number of hypoglycemic events did not differ between the trial groups. Hypoglycemic events that were recorded as adverse events at the discretion of investigators were reported in 13 participants (23%) in the golimumab group and in 2 (7%) of those in the placebo group. Antibodies to golimumab were detected in 30 participants who received the drug; 29 had antibody titers lower than 1:1000, of whom 12 had positive results for neutralizing antibodies. CONCLUSIONS: Among children and young adults with newly diagnosed overt type 1 diabetes, golimumab resulted in better endogenous insulin production and less exogenous insulin use than placebo. (Funded by Janssen Research and Development; T1GER ClinicalTrials.gov number, NCT02846545.).


Assuntos
Anticorpos Monoclonais/uso terapêutico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina/metabolismo , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adolescente , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/farmacologia , Área Sob a Curva , Peptídeo C/metabolismo , Criança , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/metabolismo , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Insulina/administração & dosagem , Insulina/efeitos adversos , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Masculino , Proinsulina/metabolismo , Adulto Jovem
5.
Pediatr Diabetes ; 20232023.
Artigo em Inglês | MEDLINE | ID: mdl-37614409

RESUMO

Background/Objective: Growth and obesity have been associated with increased risk of islet autoimmunity (IA) and progression to type 1 diabetes. We aimed to estimate the effect of energy-yielding macronutrient intake on the development of IA through BMI. Research Design and Methods: Genetically at-risk children (n = 5,084) in Finland, Germany, Sweden, and the USA, who were autoantibody negative at 2 years of age, were followed to the age of 8 years, with anthropometric measurements and 3-day food records collected biannually. Of these, 495 (9.7%) children developed IA. Mediation analysis for time-varying covariates (BMI z-score) and exposure (energy intake) was conducted. Cox proportional hazard method was used in sensitivity analysis. Results: We found an indirect effect of total energy intake (estimates: indirect effect 0.13 [0.05, 0.21]) and energy from protein (estimates: indirect effect 0.06 [0.02, 0.11]), fat (estimates: indirect effect 0.03 [0.01, 0.05]), and carbohydrates (estimates: indirect effect 0.02 [0.00, 0.04]) (kcal/day) on the development of IA. A direct effect was found for protein, expressed both as kcal/day (estimates: direct effect 1.09 [0.35, 1.56]) and energy percentage (estimates: direct effect 72.8 [3.0, 98.0]) and the development of GAD autoantibodies (GADA). In the sensitivity analysis, energy from protein (kcal/day) was associated with increased risk for GADA, hazard ratio 1.24 (95% CI: 1.09, 1.53), p = 0.042. Conclusions: This study confirms that higher total energy intake is associated with higher BMI, which leads to higher risk of the development of IA. A diet with larger proportion of energy from protein has a direct effect on the development of GADA.


Assuntos
Autoimunidade , Análise de Mediação , Criança , Humanos , Índice de Massa Corporal , Ingestão de Alimentos , Ingestão de Energia , Autoanticorpos
6.
Am J Pathol ; 191(3): 454-462, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33307036

RESUMO

Emerging data suggest that type 1 diabetes affects not only the ß-cell-containing islets of Langerhans, but also the surrounding exocrine compartment. Using digital pathology, machine learning algorithms were applied to high-resolution, whole-slide images of human pancreata to determine whether the tissue composition in individuals with or at risk for type 1 diabetes differs from those without diabetes. Transplant-grade pancreata from organ donors were evaluated from 16 nondiabetic autoantibody-negative controls, 8 nondiabetic autoantibody-positive subjects with increased type 1 diabetes risk, and 19 persons with type 1 diabetes (0 to 12 years' duration). HALO image analysis algorithms were implemented to compare architecture of the main pancreatic duct as well as cell size, density, and area of acinar, endocrine, ductal, and other nonendocrine, nonexocrine tissues. Type 1 diabetes was found to affect exocrine area, acinar cell density, and size, whereas the type of difference correlated with the presence or absence of insulin-positive cells remaining in the pancreas. These changes were not observed before disease onset, as indicated by modeling cross-sectional data from pancreata of autoantibody-positive subjects and those diagnosed with type 1 diabetes. These data provide novel insights into anatomic differences in type 1 diabetes pancreata and demonstrate that machine learning can be adapted for the evaluation of disease processes from cross-sectional data sets.


Assuntos
Algoritmos , Autoanticorpos/imunologia , Diabetes Mellitus Tipo 1/patologia , Processamento de Imagem Assistida por Computador/métodos , Aprendizado de Máquina , Pâncreas/patologia , Adolescente , Autoanticorpos/sangue , Estudos de Casos e Controles , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/metabolismo , Feminino , Humanos , Insulina/análise , Pâncreas/imunologia , Pâncreas/metabolismo , Doadores de Tecidos
7.
Pediatr Diabetes ; 23(8): 1687-1694, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36089647

RESUMO

OBJECTIVE: This study sought to examine the reliability and validity of a novel pediatric type 1 diabetes knowledge assessment (KAT-1) designed for children, adolescents, young adults and their parents/guardians. The instrument was designed to be integrated into the clinic workflow to obtain objective data electronically. RESEARCH DESIGN AND METHODS: KAT-1 was developed by a multidisciplinary team and includes 11 independent topical subscales. Forty children/caregivers participated in a pilot study; their feedback was used to improve item clarity and readability. Subsequently, a validation study was performed in 200 participants (100 children/adolescents/young adults with type 1 diabetes ages 11-21 years and 100 parents/guardians of children with type 1 diabetes ages 1-15 years) to examine correlations between the KAT-1 scores and Revised Diabetes Knowledge Test (DKT2) scores and HbA1c. An item analysis was conducted to determine internal consistency and reliability; topical subscales were evaluated using Cronbach's alpha. RESULTS: Total KAT-1 scores were positively correlated with DKT2 scores r = 0.674, p < 0.001, and negatively correlated with HbA1c, r = -0.3, p < 0.001. All KAT-1 subscales were positively and significantly correlated with one another and with total KAT-1 score. Internal consistency of total KAT-1 score was strong (Cronbach's α = 0.938, mean score 84.6, SD = 16.1) and 9 of 11 independent topical subscales demonstrated strong internal consistency. Completion time for subscales was <5 min. CONCLUSIONS: KAT-1 is a valid instrument to assess type 1 diabetes knowledge. The instrument's short topical subscales can be used to objectively assess specific knowledge and individualize diabetes education. KAT-1 has been integrated into our electronic health record (EPIC) and is available online at no cost.


Assuntos
Diabetes Mellitus Tipo 1 , Adolescente , Adulto Jovem , Humanos , Criança , Adulto , Lactente , Pré-Escolar , Reprodutibilidade dos Testes , Hemoglobinas Glicadas , Projetos Piloto , Inquéritos e Questionários , Psicometria
8.
Pediatr Diabetes ; 23(7): 1017-1026, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35702057

RESUMO

OBJECTIVE: To examine the association of physical activity (PA), measured by accelerometry, to hemoglobin AIC (HbA1c) and oral glucose tolerance test (OGTT) outcomes in children who were multiple persistent confirmed autoantibody positive for type 1 diabetes (T1D). METHODS: The Environmental Determinants of Diabetes in the Young (TEDDY) multinational study followed children from birth. Children ≥3 years of age who were multiple persistent confirmed autoantibody positive were monitored by OGTTs every 6 months. TEDDY children's PA was measured by accelerometry beginning at 5 years of age. We examined the relationship between moderate plus vigorous (mod + vig) PA, HbA1c, and OGTT in 209 multiple autoantibody children who had both OGTT and PA measurements. RESULTS: Mod + vig PA was associated with both glucose and C-peptide measures (fasting, 120-min, and AUC); higher mod + vig PA was associated with a better OGTT response primarily in children with longer duration of multiple autoantibody positivity. Mod + vig PA also interacted with child age; lower mod + vig PA was associated with a greater increase in C-peptide response across age. Mod + vig PA was not related to fasting insulin, HOMA-IR or HbA1c. CONCLUSIONS: The OGTT is the gold standard for diabetes diagnosis and is used to monitor those at high risk for T1D. We found higher levels of mod + vig PA were associated with better OGTT outcomes in children ≥5 years of age who have been multiple autoantibody positive for longer periods of time. Physical activity should be the focus of future efforts to better understand the determinants of disease progression in high-risk children.


Assuntos
Diabetes Mellitus Tipo 1 , Autoanticorpos , Glicemia , Peptídeo C , Criança , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/epidemiologia , Exercício Físico , Glucose , Teste de Tolerância a Glucose , Hemoglobinas Glicadas , Humanos , Lactente
9.
Pediatr Diabetes ; 23(8): 1586-1593, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36082496

RESUMO

OBJECTIVE: Increased level of glycated hemoglobin (HbA1c) is associated with type 1 diabetes onset that in turn is preceded by one to several autoantibodies against the pancreatic islet beta cell autoantigens; insulin (IA), glutamic acid decarboxylase (GAD), islet antigen-2 (IA-2) and zinc transporter 8 (ZnT8). The risk for type 1 diabetes diagnosis increases by autoantibody number. Biomarkers predicting the development of a second or a subsequent autoantibody and type 1 diabetes are needed to predict disease stages and improve secondary prevention trials. This study aimed to investigate whether HbA1c possibly predicts the progression from first to a subsequent autoantibody or type 1 diabetes in healthy children participating in the Environmental Determinants of Diabetes in the Young (TEDDY) study. RESEARCH DESIGN AND METHODS: A joint model was designed to assess the association of longitudinal HbA1c levels with the development of first (insulin or GAD autoantibodies) to a second, second to third, third to fourth autoantibody or type 1 diabetes in healthy children prospectively followed from birth until 15 years of age. RESULTS: It was found that increased levels of HbA1c were associated with a higher risk of type 1 diabetes (HR 1.82, 95% CI [1.57-2.10], p < 0.001) regardless of first appearing autoantibody, autoantibody number or type. A decrease in HbA1c levels was associated with the development of IA-2A as a second autoantibody following GADA (HR 0.85, 95% CI [0.75, 0.97], p = 0.017) and a fourth autoantibody following GADA, IAA and ZnT8A (HR 0.90, 95% CI [0.82, 0.99], p = 0.036). HbA1c trajectory analyses showed a significant increase of HbA1c over time (p < 0.001) and that the increase is more rapid as the number of autoantibodies increased from one to three (p < 0.001). CONCLUSION: In conclusion, increased HbA1c is a reliable time predictive marker for type 1 diabetes onset. The increased rate of increase of HbA1c from first to third autoantibody and the decrease in HbA1c predicting the development of IA-2A are novel findings proving the link between HbA1c and the appearance of autoantibodies.


Assuntos
Diabetes Mellitus Tipo 1 , Hemoglobinas Glicadas , Criança , Humanos , Autoanticorpos/sangue , Autoanticorpos/química , Biomarcadores , Diabetes Mellitus Tipo 1/diagnóstico , Glutamato Descarboxilase/imunologia , Hemoglobinas Glicadas/química , Insulina/metabolismo
10.
Diabetes Spectr ; 35(1): 33-42, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-35308158

RESUMO

The ongoing coronavirus pandemic led to a rapid and dramatic increase in the use of telehealth for diabetes care. In the wake of this transition, we examine new opportunities and ongoing challenges for using telehealth within diabetes management, based on data and experiences from the pre-pandemic and pandemic time frames.

11.
Diabetologia ; 64(11): 2432-2444, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34338806

RESUMO

AIMS/HYPOTHESIS: Accurate prediction of disease progression in individuals with pre-symptomatic type 1 diabetes has potential to prevent ketoacidosis and accelerate development of disease-modifying therapies. Current tools for predicting risk require multiple blood samples taken during an OGTT. Our aim was to develop and validate a simpler tool based on a single blood draw. METHODS: Models to predict disease progression using a single OGTT time point (0, 30, 60, 90 or 120 min) were developed using TrialNet data collected from relatives with type 1 diabetes and validated in independent populations at high genetic risk of type 1 diabetes (TrialNet, Diabetes Prevention Trial-Type 1, The Environmental Determinants of Diabetes in the Young [1]) and in a general population of Bavarian children who participated in Fr1da. RESULTS: Cox proportional hazards models combining plasma glucose, C-peptide, sex, age, BMI, HbA1c and insulinoma antigen-2 autoantibody status predicted disease progression in all populations. In TrialNet, the AUC for receiver operating characteristic curves for models named M60, M90 and M120, based on sampling at 60, 90 and 120 min, was 0.760, 0.761 and 0.745, respectively. These were not significantly different from the AUC of 0.760 for the gold standard Diabetes Prevention Trial Risk Score, which requires five OGTT blood samples. In TEDDY, where only 120 min blood sampling had been performed, the M120 AUC was 0.865. In Fr1da, the M120 AUC of 0.742 was significantly greater than the M60 AUC of 0.615. CONCLUSIONS/INTERPRETATION: Prediction models based on a single OGTT blood draw accurately predict disease progression from stage 1 or 2 to stage 3 type 1 diabetes. The operational simplicity of M120, its validity across different at-risk populations and the requirement for 120 min sampling to stage type 1 diabetes suggest M120 could be readily applied to decrease the cost and complexity of risk stratification.


Assuntos
Doenças Assintomáticas , Autoanticorpos/sangue , Diabetes Mellitus Tipo 1/diagnóstico , Anticorpos Anti-Insulina/sangue , Proteínas Tirosina Fosfatases Classe 8 Semelhantes a Receptores/imunologia , Transportador 8 de Zinco/imunologia , Adolescente , Área Sob a Curva , Glicemia/metabolismo , Índice de Massa Corporal , Peptídeo C/sangue , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/sangue , Progressão da Doença , Feminino , Teste de Tolerância a Glucose , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino , Modelos de Riscos Proporcionais , Curva ROC
12.
J Theor Biol ; 528: 110853, 2021 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-34358537

RESUMO

Current clinician practice for thyroid hormone regulation of patients is based upon guesswork and experience rather than quantified analysis, which exposes patients under longer risk and discomfort. To quantitatively analyze the thyroid regulation for patients of different thyroid states, we develop a two-dimensional mathematical model that can be applied to analyze the dynamic behaviors of thyroid hormones with or without drug intervention. The unified model can be employed to study the regulation of TSH (thyroid-stimulating hormone) and FT4 (free thyroxine) for euthyroid (normal thyroid) subjects, Hashimoto's thyroiditis, and Graves' disease patients, respectively. The results suggest that the level of TPOAb (thyroid peroxidase antibody) may be a factor determining whether the patient would progress from euthyroid state to subclinical or clinical hypothyroidism, and that increased TRAb (TSH receptor antibody) may lead Graves' disease to deteriorate from the early stage to overt hyperthyroidism. Given the early blood-test data, we demonstrate the feasibility for healthcare professionals to apply our model in choosing an appropriate dosage regimen for patients to achieve the desired TSH and FT4 levels within a specified time frame. This proposed model has the potential to optimize personalized treatment and shorten the therapeutic time for patients suffering from Hashimoto's thyroiditis and Graves' disease.


Assuntos
Doença de Graves , Medicina de Precisão , Autoanticorpos , Doença de Graves/tratamento farmacológico , Humanos , Modelos Teóricos , Hormônios Tireóideos
13.
Pediatr Diabetes ; 22(2): 360-368, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33179853

RESUMO

OBJECTIVE: To examine adherence to the oral glucose tolerance test (OGTT) in multiple islet autoantibody children in stage 1 of developing type 1 diabetes (T1D). METHODS: Children are followed from birth in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Completion of an OGTT is recommended every 6 months in children ≥3 years of age who are multiple islet autoantibody positive. Factors associated with adherence to the OGTT protocol were examined. RESULTS: The average subject level adherence with the OGTT protocol was 62% although there were large differences across countries; Finnish participants and older children from Sweden were more adherent than participants from the United States and Germany. Factors associated with nonadherence included having a first-degree relative with T1D, using a local laboratory rather than a TEDDY center for the OGTT, and maternal underestimation of the child's risk for T1D. Children were more adherent to the OGTT if their mothers: were more satisfied with TEDDY participation, reported monitoring the child for T1D by checking blood glucose levels at home, and viewed participating in TEDDY as the primary way they were monitoring the child for T1D. CONCLUSIONS: In a study of children in stage 1 of T1D, adherence to an OGTT protocol was suboptimal despite extensive efforts to communicate the child's high risk to parents. These findings provide important guidance for development of strategies to improve methods for detecting progression or the development of T1D in high-risk pediatric populations.


Assuntos
Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/psicologia , Teste de Tolerância a Glucose , Cooperação do Paciente , Autoanticorpos/sangue , Criança , Diabetes Mellitus Tipo 1/sangue , Feminino , Finlândia , Alemanha , Humanos , Ilhotas Pancreáticas/imunologia , Masculino , Suécia , Estados Unidos
14.
Pediatr Rev ; 42(Suppl 2): 173-176, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34470902

RESUMO

Cysts of the external female genitalia are uncommon findings and can be either congenital or acquired. Congenital cysts of the external female genitalia may be discovered from the initial newborn examination and cause concern for clitoromegaly or ambiguous genitalia. We describe a clitoral cyst presenting as apparent clitoromegaly in a newborn; this is the third reported case in the literature. We also review the differential and evaluation for clitoromegaly in a newborn. We present a case of a 1-day-old newborn, with concern for clitoromegaly on initial newborn examination. Multiple anatomy ultrasounds were performed during pregnancy and no genital abnormality was noted. On physical examination, a 1 × 1 cm cyst was found on the clitoral hood obstructing the clitoris and vaginal opening. There were no signs of virilization or hyperandrogenism on examination. The cyst was aspirated, with clear, serous fluid removed. Normal female anatomy and normal clitoris size were noted after aspiration. She had no recurrence of the cyst in the months after discharge. Clitoral cysts of the female external genitalia are rare findings. Baring signs of virilization of hyperandrogenism, conservative management and watchful waiting or cyst drainage are reasonable approaches.


Assuntos
Hiperandrogenismo , Doenças da Vulva , Clitóris , Feminino , Humanos , Recém-Nascido , Recidiva Local de Neoplasia , Gravidez , Ultrassonografia
15.
J Autoimmun ; 108: 102417, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32035746

RESUMO

IL-12 and IL-18 synergize to promote TH1 responses and have been implicated as accelerators of autoimmune pathogenesis in type 1 diabetes (T1D). We investigated the influence of these cytokines on immune cells involved in human T1D progression: natural killer (NK) cells, regulatory T cells (Tregs), and cytotoxic T lymphocytes (CTL). NK cells from T1D patients exhibited higher surface CD226 versus controls and lower CD25 compared to first-degree relatives and controls. Changes in NK cell phenotype towards terminal differentiation were associated with cytomegalovirus (CMV) seropositivity, while possession of IL18RAP, IFIH1, and IL2RA T1D-risk variants impacted NK cell activation as evaluated by immuno-expression quantitative trait loci (eQTL) analyses. IL-12 and IL-18 stimulated NK cells from healthy donors exhibited enhanced specific killing of myelogenous K562 target cells. Moreover, activated NK cells increased expression of NKG2A, NKG2D, CD226, TIGIT and CD25, which enabled competition for IL-2 upon co-culture with Tregs, resulting in Treg downregulation of FOXP3, production of IFNγ, and loss of suppressive function. We generated islet-autoreactive CTL "avatars", which upon exposure to IL-12 and IL-18, upregulated IFNγ and Granzyme-B leading to increased lymphocytotoxicity of a human ß-cell line in vitro. These results support a model for T1D pathogenesis wherein IL-12 and IL-18 synergistically enhance CTL and NK cell cytotoxic activity and disrupt immunoregulation by Tregs.


Assuntos
Imunidade Inata , Inflamação/imunologia , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Ativação Linfocitária/imunologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Adolescente , Adulto , Biomarcadores , Células Cultivadas , Criança , Citocinas/metabolismo , Citotoxicidade Imunológica , Diabetes Mellitus Tipo 1/etiologia , Diabetes Mellitus Tipo 1/metabolismo , Suscetibilidade a Doenças , Feminino , Humanos , Imunofenotipagem , Inflamação/metabolismo , Inflamação/patologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Fenótipo , Locos de Características Quantitativas , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/metabolismo , Adulto Jovem
16.
Pediatr Diabetes ; 21(1): 120-127, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31617648

RESUMO

Pronounced health disparities exist in type 1 diabetes (T1D) based on socioeconomic status (SES) yet there are a lack of programs designed to promote health equity for vulnerable communities. The All for ONE (Outreach, Networks, and Education) mentoring program was piloted pairing college students and publicly insured teenagers with T1D to assess feasibility as a possible intervention. There were 22 mentors recruited (mean age 20 ± 2 years; 17 [77%] females; mean HbA1c 8.4 ± 1.5%) and matched with mentees based on gender. There were 42 teens randomized to treatment and control groups including 22 teens in the treatment group (age 14 ± 2 years; 17 [77%] females; HbA1c 9.8 ± 2.3%) and 20 teens in the control group (age 14 ± 2 years; 15 [75%] females; HbA1c 8.9 ± 2.0%) followed over 9 months. Outcome measures included HbA1c and the Children's Hope Scale. The intervention included automated text reminders for blood glucose monitoring, text exchanges, social events with education, and clinic visits with mentors/mentees. Mean change in HbA1c for teens was +0.09% in the intervention group, compared with +0.28% in the control group (P = .61); college students had a reduction in HbA1c of -0.22% (P = .38). Treatment group teens had marked improvement in their hope for the future compared to control group teens (P = .04) and were more likely to attend clinic visits (P = .02). This program established feasibility for a model that could be replicated and modified for other types of settings. Additional research is warranted to study the potential long-term benefits of participating in the All for ONE mentoring program.


Assuntos
Diabetes Mellitus Tipo 1/terapia , Promoção da Saúde/métodos , Disparidades nos Níveis de Saúde , Mentores , Adolescente , Fatores Etários , Automonitorização da Glicemia , Criança , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/psicologia , Estudos de Viabilidade , Feminino , Hemoglobinas Glicadas/metabolismo , Esperança , Humanos , Masculino , Grupo Associado , Fatores Socioeconômicos , Adulto Jovem
17.
Endocr Pract ; 26(12): 1505-1513, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33471743

RESUMO

OBJECTIVE: Type 1 diabetes (T1D) is characterized by autoimmune ß-cell destruction, but exocrine pancreas abnormalities may also play a role in the disease pathophysiology. Herein, we review the current evidence of exocrine damage in T1D and discuss its underlying pathophysiology, clinical evaluation, and treatment. METHOD: Extensive literature search was performed for "type 1 diabetes" and "exocrine dysfunction" on PubMed and Google Scholar databases. RESULTS: T1D pancreata are significantly smaller than controls, both in weight and volume. T cells, dendritic cells, neutrophils, and products of complement activation are seen in T1D exocrine tissues. Exocrine pancreas fibrosis, arteriosclerosis, fatty infiltration, and acinar atrophy are also observed on histology. Pancreatic exocrine insufficiency (PEI) can be assessed through direct exocrine testing, fecal elastase concentration, and measurement of serum exocrine enzymes. The prevalence of PEI in T1D varies by modality and study but is consistently greater than controls. The clinical relevance of PEI in T1D is debatable, as many patients with laboratory evidence of PEI are asymptomatic. However, in PEI-symptomatic patients reported benefits of pancreatic enzyme replacement therapy (PERT) include relief of gastrointestinal symptoms, improved quality of life, better glycemic control, and optimal nutrition. CONCLUSION: Exocrine pancreas abnormalities often occur in T1D. Whether exocrine dysfunction occurs simultaneously with ß-cell destruction, as a result of ß-cell loss, or as a combination of both remains to be definitively answered. In T1D with gastrointestinal complaints, PEI should be evaluated, usually via fecal elastase measurements. PERT is recommended for T1D patients with symptoms and laboratory evidence of PEI. ABBREVIATIONS: AAb+ = autoantibody positive; AAb- = autoantibody negative; FEC = fecal elastase concentration; PEI = pancreatic exocrine insufficiency; PERT = pancreatic enzyme replacement therapy; PP = pancreatic polypep-tide; T1D = type 1 diabetes.


Assuntos
Diabetes Mellitus Tipo 1 , Insuficiência Pancreática Exócrina , Pâncreas Exócrino , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/epidemiologia , Terapia de Reposição de Enzimas , Insuficiência Pancreática Exócrina/tratamento farmacológico , Insuficiência Pancreática Exócrina/epidemiologia , Insuficiência Pancreática Exócrina/etiologia , Humanos , Pâncreas , Qualidade de Vida
18.
Diabetes Spectr ; 33(3): 280-289, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32848350

RESUMO

OBJECTIVE: Daily self-monitoring of blood glucose (SMBG) is essential for type 1 diabetes management yet is challenging during adolescence. Ecological momentary assessment (EMA) is the repeated sampling of behaviors and experiences in real time in the natural environment. The purpose of this study was to evaluate 1) the validity of self-reported SMBG values via text message-delivered EMA surveys compared with objective SMBG values via glucose meters and 2) in-the-moment motivators and barriers to performing SMBG in a pediatric type 1 diabetes population. METHODS: Youth (n = 62, aged 11-21 years) with type 1 diabetes received three text messages daily for 10 days containing surveys inquiring about SMBG engagement. Objective SMBG values were downloaded from glucose meters. RESULTS: On average, participants reported performing SMBG 4 times/day. Of the self-reported SMBG values, 39.6% were accurate. Inaccurate values included additions (i.e., self-reported value with no objective value), omissions (i.e., objective value with no self-reported value), and alterations (difference between self-report and objective SMBG values ≥10 mg/dL). Of the matched pairs of self-reported and objective SMBG values, 41.3% were altered. Bland-Altman plots determined that the mean difference between self-reported and objective glucose data were -5.43 mg/dL. Participants reported being motivated to check their blood glucose because it was important for their health, and reported barriers included wanting to ignore the task, forgetting, and not having devices. CONCLUSION: Youth's self-reported SMBG values may not align with objective readings. The results of this study can facilitate future research to determine individual factors related to SMBG and accuracy of self-reporting.

19.
Clin Diabetes ; 38(2): 159-165, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32327888

RESUMO

People with type 1 diabetes may receive a significant portion of their care from primary care providers (PCPs). To understand the involvement of PCPs in delivering type 1 diabetes care, we performed surveys in California and Florida, two of the most populous and diverse states in the United States. PCPs fill insulin prescriptions but report low confidence in providing type 1 diabetes care and difficulty accessing specialty referrals to endocrinologists.

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